<?xml version="1.0" encoding="us-ascii"?>
<!--XBRL document created with Toppan Merrill Bridge  10.2.5.9 -->
<!--Based on XBRL 2.1-->
<!--Created on: 5/1/2023 7:57:59 PM-->
<!--Modified on: 5/1/2023 7:57:59 PM-->
<link:linkbase xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.xbrl.org/2003/linkbase http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd" xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xbrli="http://www.xbrl.org/2003/instance">
  <roleRef xlink:type="simple" xlink:href="hrmy-20230331.xsd#StatementUnauditedCondensedConsolidatedBalanceSheets" roleURI="http://www.harmonybiosciences.com/role/StatementUnauditedCondensedConsolidatedBalanceSheets" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="hrmy-20230331.xsd#StatementUnauditedCondensedConsolidatedStatementsOfOperationsAndComprehensiveIncome" roleURI="http://www.harmonybiosciences.com/role/StatementUnauditedCondensedConsolidatedStatementsOfOperationsAndComprehensiveIncome" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="hrmy-20230331.xsd#StatementConsolidatedStatementsOfOperationsAndComprehensiveIncomeLossCalc2" roleURI="http://www.harmonybiosciences.com/role/StatementConsolidatedStatementsOfOperationsAndComprehensiveIncomeLossCalc2" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="hrmy-20230331.xsd#StatementUnauditedCondensedConsolidatedStatementsOfCashFlows" roleURI="http://www.harmonybiosciences.com/role/StatementUnauditedCondensedConsolidatedStatementsOfCashFlows" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="hrmy-20230331.xsd#DisclosureSummaryOfSignificantAccountingPoliciesScheduleOfReconciliationOfCashCashEquivalentsAndRestrictedCashDetails" roleURI="http://www.harmonybiosciences.com/role/DisclosureSummaryOfSignificantAccountingPoliciesScheduleOfReconciliationOfCashCashEquivalentsAndRestrictedCashDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="hrmy-20230331.xsd#DisclosureInvestmentsCarryingValueAndAmortizedCostOfAvailableForSaleDebtSecuritiesDetails" roleURI="http://www.harmonybiosciences.com/role/DisclosureInvestmentsCarryingValueAndAmortizedCostOfAvailableForSaleDebtSecuritiesDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="hrmy-20230331.xsd#DisclosureInventoryDetails" roleURI="http://www.harmonybiosciences.com/role/DisclosureInventoryDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="hrmy-20230331.xsd#DisclosureIntangibleAssetsScheduleOfExpectedFutureAnnualAmortizationExpenseForUnamortizedIntangibleAssetsDetails" roleURI="http://www.harmonybiosciences.com/role/DisclosureIntangibleAssetsScheduleOfExpectedFutureAnnualAmortizationExpenseForUnamortizedIntangibleAssetsDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="hrmy-20230331.xsd#DisclosureIntangibleAssetsScheduleOfGrossCarryingAmountAndNetBookValueOfIntangibleAssetsDetails" roleURI="http://www.harmonybiosciences.com/role/DisclosureIntangibleAssetsScheduleOfGrossCarryingAmountAndNetBookValueOfIntangibleAssetsDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="hrmy-20230331.xsd#DisclosureDebtBalancesOfLongTermDebtNetDetailsCalc2" roleURI="http://www.harmonybiosciences.com/role/DisclosureDebtBalancesOfLongTermDebtNetDetailsCalc2" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="hrmy-20230331.xsd#DisclosureAccruedExpensesDetails" roleURI="http://www.harmonybiosciences.com/role/DisclosureAccruedExpensesDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="hrmy-20230331.xsd#DisclosureLeasesFuturePaymentsDetailsCalc2" roleURI="http://www.harmonybiosciences.com/role/DisclosureLeasesFuturePaymentsDetailsCalc2" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="hrmy-20230331.xsd#DisclosureDebtBalancesOfLongTermDebtNetDetails" roleURI="http://www.harmonybiosciences.com/role/DisclosureDebtBalancesOfLongTermDebtNetDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="hrmy-20230331.xsd#DisclosureDebtFutureMinimumPaymentsDetails" roleURI="http://www.harmonybiosciences.com/role/DisclosureDebtFutureMinimumPaymentsDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="hrmy-20230331.xsd#DisclosureDebtInterestExpenseDetails" roleURI="http://www.harmonybiosciences.com/role/DisclosureDebtInterestExpenseDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="hrmy-20230331.xsd#DisclosureLeasesSupplementalBalanceSheetInformationDetails" roleURI="http://www.harmonybiosciences.com/role/DisclosureLeasesSupplementalBalanceSheetInformationDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="hrmy-20230331.xsd#DisclosureLeasesFuturePaymentsDetails" roleURI="http://www.harmonybiosciences.com/role/DisclosureLeasesFuturePaymentsDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="hrmy-20230331.xsd#DisclosureIncomeTaxesScheduleOfDifferenceBetweenStatutoryFederalIncomeTaxRateDetails" roleURI="http://www.harmonybiosciences.com/role/DisclosureIncomeTaxesScheduleOfDifferenceBetweenStatutoryFederalIncomeTaxRateDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <calculationLink xlink:role="http://www.harmonybiosciences.com/role/StatementUnauditedCondensedConsolidatedBalanceSheets" xlink:type="extended" xlink:title="00100 - Statement - UNAUDITED CONDENSED CONSOLIDATED BALANCE SHEETS" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_Assets" xlink:label="us-gaap_Assets_637684186481682065" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AssetsCurrent" xlink:label="us-gaap_AssetsCurrent_638185678770688474" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Assets_637684186481682065" xlink:to="us-gaap_AssetsCurrent_638185678770688474" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CashAndCashEquivalentsAtCarryingValue" xlink:label="us-gaap_CashAndCashEquivalentsAtCarryingValue_638185678770688474" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsCurrent_638185678770688474" xlink:to="us-gaap_CashAndCashEquivalentsAtCarryingValue_638185678770688474" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ShortTermInvestments" xlink:label="us-gaap_ShortTermInvestments_638185678770688474" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsCurrent_638185678770688474" xlink:to="us-gaap_ShortTermInvestments_638185678770688474" order="2" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AccountsReceivableNetCurrent" xlink:label="us-gaap_AccountsReceivableNetCurrent_638185678770698477" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsCurrent_638185678770688474" xlink:to="us-gaap_AccountsReceivableNetCurrent_638185678770698477" order="3" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_InventoryNet" xlink:label="us-gaap_InventoryNet_638185678770698477" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsCurrent_638185678770688474" xlink:to="us-gaap_InventoryNet_638185678770698477" order="4" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_PrepaidExpenseCurrent" xlink:label="us-gaap_PrepaidExpenseCurrent_638185678770698477" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsCurrent_638185678770688474" xlink:to="us-gaap_PrepaidExpenseCurrent_638185678770698477" order="5" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_OtherAssetsCurrent" xlink:label="us-gaap_OtherAssetsCurrent_638185678770698477" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsCurrent_638185678770688474" xlink:to="us-gaap_OtherAssetsCurrent_638185678770698477" order="6" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AssetsNoncurrent" xlink:label="us-gaap_AssetsNoncurrent_638185678770698477" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Assets_637684186481682065" xlink:to="us-gaap_AssetsNoncurrent_638185678770698477" order="2" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_PropertyPlantAndEquipmentNet" xlink:label="us-gaap_PropertyPlantAndEquipmentNet_638185678770698477" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsNoncurrent_638185678770698477" xlink:to="us-gaap_PropertyPlantAndEquipmentNet_638185678770698477" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_RestrictedCashNoncurrent" xlink:label="us-gaap_RestrictedCashNoncurrent_638185678770698477" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsNoncurrent_638185678770698477" xlink:to="us-gaap_RestrictedCashNoncurrent_638185678770698477" order="2" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LongTermInvestments" xlink:label="us-gaap_LongTermInvestments_638185678770698477" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsNoncurrent_638185678770698477" xlink:to="us-gaap_LongTermInvestments_638185678770698477" order="3" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_IntangibleAssetsNetExcludingGoodwill" xlink:label="us-gaap_IntangibleAssetsNetExcludingGoodwill_638185678770698477" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsNoncurrent_638185678770698477" xlink:to="us-gaap_IntangibleAssetsNetExcludingGoodwill_638185678770698477" order="4" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DeferredIncomeTaxAssetsNet" xlink:label="us-gaap_DeferredIncomeTaxAssetsNet_638185678770708477" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsNoncurrent_638185678770698477" xlink:to="us-gaap_DeferredIncomeTaxAssetsNet_638185678770708477" order="5" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_OtherAssetsNoncurrent" xlink:label="us-gaap_OtherAssetsNoncurrent_638185678770708477" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsNoncurrent_638185678770698477" xlink:to="us-gaap_OtherAssetsNoncurrent_638185678770708477" order="6" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LiabilitiesAndStockholdersEquity" xlink:label="us-gaap_LiabilitiesAndStockholdersEquity_637684186481682065" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_Liabilities" xlink:label="us-gaap_Liabilities_638185678770708477" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesAndStockholdersEquity_637684186481682065" xlink:to="us-gaap_Liabilities_638185678770708477" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LiabilitiesCurrent" xlink:label="us-gaap_LiabilitiesCurrent_638185678770708477" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Liabilities_638185678770708477" xlink:to="us-gaap_LiabilitiesCurrent_638185678770708477" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AccountsPayableCurrent" xlink:label="us-gaap_AccountsPayableCurrent_638185678770708477" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesCurrent_638185678770708477" xlink:to="us-gaap_AccountsPayableCurrent_638185678770708477" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AccruedEmployeeBenefitsCurrent" xlink:label="us-gaap_AccruedEmployeeBenefitsCurrent_638185678770708477" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesCurrent_638185678770708477" xlink:to="us-gaap_AccruedEmployeeBenefitsCurrent_638185678770708477" order="2" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AccruedLiabilitiesCurrent" xlink:label="us-gaap_AccruedLiabilitiesCurrent_638185678770718482" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesCurrent_638185678770708477" xlink:to="us-gaap_AccruedLiabilitiesCurrent_638185678770718482" order="3" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LongTermDebtCurrent" xlink:label="us-gaap_LongTermDebtCurrent_638185678770718482" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesCurrent_638185678770708477" xlink:to="us-gaap_LongTermDebtCurrent_638185678770718482" order="4" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_OtherLiabilitiesCurrent" xlink:label="us-gaap_OtherLiabilitiesCurrent_638185678770718482" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesCurrent_638185678770708477" xlink:to="us-gaap_OtherLiabilitiesCurrent_638185678770718482" order="5" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LiabilitiesNoncurrent" xlink:label="us-gaap_LiabilitiesNoncurrent_638185678770718482" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Liabilities_638185678770708477" xlink:to="us-gaap_LiabilitiesNoncurrent_638185678770718482" order="2" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LongTermDebtNoncurrent" xlink:label="us-gaap_LongTermDebtNoncurrent_638185678770718482" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesNoncurrent_638185678770718482" xlink:to="us-gaap_LongTermDebtNoncurrent_638185678770718482" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_OtherLiabilitiesNoncurrent" xlink:label="us-gaap_OtherLiabilitiesNoncurrent_638185678770718482" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesNoncurrent_638185678770718482" xlink:to="us-gaap_OtherLiabilitiesNoncurrent_638185678770718482" order="2" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CommitmentsAndContingencies" xlink:label="us-gaap_CommitmentsAndContingencies_638185678770718482" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesAndStockholdersEquity_637684186481682065" xlink:to="us-gaap_CommitmentsAndContingencies_638185678770718482" order="2" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_StockholdersEquity" xlink:label="us-gaap_StockholdersEquity_638185678770728543" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesAndStockholdersEquity_637684186481682065" xlink:to="us-gaap_StockholdersEquity_638185678770728543" order="3" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CommonStockValue" xlink:label="us-gaap_CommonStockValue_638185678770728543" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_StockholdersEquity_638185678770728543" xlink:to="us-gaap_CommonStockValue_638185678770728543" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AdditionalPaidInCapitalCommonStock" xlink:label="us-gaap_AdditionalPaidInCapitalCommonStock_638185678770728543" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_StockholdersEquity_638185678770728543" xlink:to="us-gaap_AdditionalPaidInCapitalCommonStock_638185678770728543" order="2" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax" xlink:label="us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax_638185678770728543" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_StockholdersEquity_638185678770728543" xlink:to="us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax_638185678770728543" order="3" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_RetainedEarningsAccumulatedDeficit" xlink:label="us-gaap_RetainedEarningsAccumulatedDeficit_638185678770728543" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_StockholdersEquity_638185678770728543" xlink:to="us-gaap_RetainedEarningsAccumulatedDeficit_638185678770728543" order="4" use="optional" weight="1" priority="2" />
  </calculationLink>
  <calculationLink xlink:role="http://www.harmonybiosciences.com/role/StatementUnauditedCondensedConsolidatedStatementsOfOperationsAndComprehensiveIncome" xlink:type="extended" xlink:title="00200 - Statement - UNAUDITED CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS AND COMPREHENSIVE INCOME" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ComprehensiveIncomeNetOfTax" xlink:label="us-gaap_ComprehensiveIncomeNetOfTax" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" xlink:label="us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent_638185678770738480" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_ComprehensiveIncomeNetOfTax" xlink:to="us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent_638185678770738480" order="1" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_NetIncomeLoss" xlink:label="us-gaap_NetIncomeLoss_638185678770738480" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_ComprehensiveIncomeNetOfTax" xlink:to="us-gaap_NetIncomeLoss_638185678770738480" order="2" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_IncomeTaxExpenseBenefit" xlink:label="us-gaap_IncomeTaxExpenseBenefit_638185678770738480" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetIncomeLoss_638185678770738480" xlink:to="us-gaap_IncomeTaxExpenseBenefit_638185678770738480" order="1" use="optional" weight="-1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" xlink:label="us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_638185678770738480" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetIncomeLoss_638185678770738480" xlink:to="us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_638185678770738480" order="2" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_InterestIncomeExpenseNonoperatingNet" xlink:label="us-gaap_InterestIncomeExpenseNonoperatingNet_638185678770738480" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_638185678770738480" xlink:to="us-gaap_InterestIncomeExpenseNonoperatingNet_638185678770738480" order="1" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_OtherNonoperatingIncomeExpense" xlink:label="us-gaap_OtherNonoperatingIncomeExpense_638185678770738480" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_638185678770738480" xlink:to="us-gaap_OtherNonoperatingIncomeExpense_638185678770738480" order="2" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_OperatingIncomeLoss" xlink:label="us-gaap_OperatingIncomeLoss_638185678770738480" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_638185678770738480" xlink:to="us-gaap_OperatingIncomeLoss_638185678770738480" order="3" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_OperatingExpenses" xlink:label="us-gaap_OperatingExpenses_638185678770738480" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_OperatingIncomeLoss_638185678770738480" xlink:to="us-gaap_OperatingExpenses_638185678770738480" order="1" use="optional" weight="-1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_GeneralAndAdministrativeExpense" xlink:label="us-gaap_GeneralAndAdministrativeExpense_638185678770738480" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_OperatingExpenses_638185678770738480" xlink:to="us-gaap_GeneralAndAdministrativeExpense_638185678770738480" order="1" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_SellingAndMarketingExpense" xlink:label="us-gaap_SellingAndMarketingExpense_638185678770738480" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_OperatingExpenses_638185678770738480" xlink:to="us-gaap_SellingAndMarketingExpense_638185678770738480" order="2" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ResearchAndDevelopmentExpense" xlink:label="us-gaap_ResearchAndDevelopmentExpense_638185678770748476" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_OperatingExpenses_638185678770738480" xlink:to="us-gaap_ResearchAndDevelopmentExpense_638185678770748476" order="3" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_GrossProfit" xlink:label="us-gaap_GrossProfit_638185678770748476" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_OperatingIncomeLoss_638185678770738480" xlink:to="us-gaap_GrossProfit_638185678770748476" order="2" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax" xlink:label="us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_638185678770748476" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_GrossProfit_638185678770748476" xlink:to="us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_638185678770748476" order="1" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CostOfGoodsAndServicesSold" xlink:label="us-gaap_CostOfGoodsAndServicesSold_638185678770748476" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_GrossProfit_638185678770748476" xlink:to="us-gaap_CostOfGoodsAndServicesSold_638185678770748476" order="2" use="optional" weight="-1" />
  </calculationLink>
  <calculationLink xlink:role="http://www.harmonybiosciences.com/role/StatementConsolidatedStatementsOfOperationsAndComprehensiveIncomeLossCalc2" xlink:type="extended" xlink:title="00300 - Statement - CONSOLIDATED STATEMENTS OF OPERATIONS AND COMPREHENSIVE INCOME (LOSS) calc 2" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_NetIncomeLossAvailableToCommonStockholdersBasic" xlink:label="us-gaap_NetIncomeLossAvailableToCommonStockholdersBasic_1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_NetIncomeLoss" xlink:label="us-gaap_NetIncomeLoss_638185678770748476" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetIncomeLossAvailableToCommonStockholdersBasic_1" xlink:to="us-gaap_NetIncomeLoss_638185678770748476" order="1" use="optional" weight="1" />
  </calculationLink>
  <calculationLink xlink:role="http://www.harmonybiosciences.com/role/StatementUnauditedCondensedConsolidatedStatementsOfCashFlows" xlink:type="extended" xlink:title="00400 - Statement - UNAUDITED CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" xlink:label="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:label="us-gaap_NetCashProvidedByUsedInOperatingActivities_638185678770748476" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" xlink:to="us-gaap_NetCashProvidedByUsedInOperatingActivities_638185678770748476" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ProfitLoss" xlink:label="us-gaap_ProfitLoss_638185678770758478" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_638185678770748476" xlink:to="us-gaap_ProfitLoss_638185678770758478" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_OtherNoncashExpense" xlink:label="us-gaap_OtherNoncashExpense_638185678770758478" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_638185678770748476" xlink:to="us-gaap_OtherNoncashExpense_638185678770758478" order="2" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_Depreciation" xlink:label="us-gaap_Depreciation_638185678770758478" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_638185678770748476" xlink:to="us-gaap_Depreciation_638185678770758478" order="3" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AmortizationOfIntangibleAssets" xlink:label="us-gaap_AmortizationOfIntangibleAssets_638185678770758478" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_638185678770748476" xlink:to="us-gaap_AmortizationOfIntangibleAssets_638185678770758478" order="4" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ShareBasedCompensation" xlink:label="us-gaap_ShareBasedCompensation_638185678770758478" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_638185678770748476" xlink:to="us-gaap_ShareBasedCompensation_638185678770758478" order="5" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="hrmy-20230331.xsd#hrmy_StockAppreciationRightsMarketAdjustment" xlink:label="hrmy_StockAppreciationRightsMarketAdjustment_638185678770758478" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_638185678770748476" xlink:to="hrmy_StockAppreciationRightsMarketAdjustment_638185678770758478" order="6" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DeferredIncomeTaxesAndTaxCredits" xlink:label="us-gaap_DeferredIncomeTaxesAndTaxCredits_638185678770758478" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_638185678770748476" xlink:to="us-gaap_DeferredIncomeTaxesAndTaxCredits_638185678770758478" order="7" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AmortizationOfFinancingCosts" xlink:label="us-gaap_AmortizationOfFinancingCosts_638185678770758478" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_638185678770748476" xlink:to="us-gaap_AmortizationOfFinancingCosts_638185678770758478" order="8" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_IncreaseDecreaseInAccountsReceivable" xlink:label="us-gaap_IncreaseDecreaseInAccountsReceivable_638185678770758478" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_638185678770748476" xlink:to="us-gaap_IncreaseDecreaseInAccountsReceivable_638185678770758478" order="9" use="optional" weight="-1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_IncreaseDecreaseInInventories" xlink:label="us-gaap_IncreaseDecreaseInInventories_638185678770768479" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_638185678770748476" xlink:to="us-gaap_IncreaseDecreaseInInventories_638185678770768479" order="10" use="optional" weight="-1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_IncreaseDecreaseInPrepaidDeferredExpenseAndOtherAssets" xlink:label="us-gaap_IncreaseDecreaseInPrepaidDeferredExpenseAndOtherAssets_638185678770768479" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_638185678770748476" xlink:to="us-gaap_IncreaseDecreaseInPrepaidDeferredExpenseAndOtherAssets_638185678770768479" order="11" use="optional" weight="-1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_IncreaseDecreaseInAccountsPayableTrade" xlink:label="us-gaap_IncreaseDecreaseInAccountsPayableTrade_638185678770768479" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_638185678770748476" xlink:to="us-gaap_IncreaseDecreaseInAccountsPayableTrade_638185678770768479" order="12" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_IncreaseDecreaseInAccruedLiabilitiesAndOtherOperatingLiabilities" xlink:label="us-gaap_IncreaseDecreaseInAccruedLiabilitiesAndOtherOperatingLiabilities_638185678770768479" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_638185678770748476" xlink:to="us-gaap_IncreaseDecreaseInAccruedLiabilitiesAndOtherOperatingLiabilities_638185678770768479" order="13" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_IncreaseDecreaseInOtherNoncurrentLiabilities" xlink:label="us-gaap_IncreaseDecreaseInOtherNoncurrentLiabilities_638185678770768479" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_638185678770748476" xlink:to="us-gaap_IncreaseDecreaseInOtherNoncurrentLiabilities_638185678770768479" order="14" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AccretionAmortizationOfDiscountsAndPremiumsInvestments" xlink:label="us-gaap_AccretionAmortizationOfDiscountsAndPremiumsInvestments_638185678770768479" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_638185678770748476" xlink:to="us-gaap_AccretionAmortizationOfDiscountsAndPremiumsInvestments_638185678770768479" order="15" use="optional" weight="-1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_NetCashProvidedByUsedInInvestingActivities" xlink:label="us-gaap_NetCashProvidedByUsedInInvestingActivities_638185678770768479" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" xlink:to="us-gaap_NetCashProvidedByUsedInInvestingActivities_638185678770768479" order="2" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt" xlink:label="us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt_638185678770768479" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInInvestingActivities_638185678770768479" xlink:to="us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt_638185678770768479" order="1" use="optional" weight="-1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" xlink:label="us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities_638185678770778477" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInInvestingActivities_638185678770768479" xlink:to="us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities_638185678770778477" order="2" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_PaymentsToAcquirePropertyPlantAndEquipment" xlink:label="us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_638185678770778477" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInInvestingActivities_638185678770768479" xlink:to="us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_638185678770778477" order="3" use="optional" weight="-1" priority="2" />
    <loc xlink:type="locator" xlink:href="hrmy-20230331.xsd#hrmy_CashPaidForMilestones" xlink:label="hrmy_CashPaidForMilestones_638185678770778477" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInInvestingActivities_638185678770768479" xlink:to="hrmy_CashPaidForMilestones_638185678770778477" order="4" use="optional" weight="-1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_NetCashProvidedByUsedInFinancingActivities" xlink:label="us-gaap_NetCashProvidedByUsedInFinancingActivities_638185678770778477" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" xlink:to="us-gaap_NetCashProvidedByUsedInFinancingActivities_638185678770778477" order="3" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ProceedsFromStockOptionsExercised" xlink:label="us-gaap_ProceedsFromStockOptionsExercised_638185678770778477" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInFinancingActivities_638185678770778477" xlink:to="us-gaap_ProceedsFromStockOptionsExercised_638185678770778477" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_RepaymentsOfLongTermDebt" xlink:label="us-gaap_RepaymentsOfLongTermDebt_638185678770778477" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInFinancingActivities_638185678770778477" xlink:to="us-gaap_RepaymentsOfLongTermDebt_638185678770778477" order="2" use="optional" weight="-1" />
  </calculationLink>
  <calculationLink xlink:role="http://www.harmonybiosciences.com/role/DisclosureSummaryOfSignificantAccountingPoliciesScheduleOfReconciliationOfCashCashEquivalentsAndRestrictedCashDetails" xlink:type="extended" xlink:title="40301 - Disclosure - Summary of Significant Accounting Policies - Schedule of Reconciliation of Cash, Cash Equivalents, and Restricted Cash (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" xlink:label="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CashAndCashEquivalentsAtCarryingValue" xlink:label="us-gaap_CashAndCashEquivalentsAtCarryingValue_638185678770788477" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" xlink:to="us-gaap_CashAndCashEquivalentsAtCarryingValue_638185678770788477" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_RestrictedCashNoncurrent" xlink:label="us-gaap_RestrictedCashNoncurrent_638185678770788477" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" xlink:to="us-gaap_RestrictedCashNoncurrent_638185678770788477" order="2" use="optional" weight="1" priority="2" />
  </calculationLink>
  <calculationLink xlink:role="http://www.harmonybiosciences.com/role/DisclosureInvestmentsCarryingValueAndAmortizedCostOfAvailableForSaleDebtSecuritiesDetails" xlink:type="extended" xlink:title="40401 - Disclosure - Investments - Carrying Value and Amortized Cost of Available-For-Sale Debt Securities (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis" xlink:label="us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" xlink:label="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_638185678770788477" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis" xlink:to="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_638185678770788477" order="1" use="optional" weight="-1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" xlink:label="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_638185678770788477" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis" xlink:to="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_638185678770788477" order="2" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities" xlink:label="us-gaap_AvailableForSaleSecuritiesDebtSecurities_638185678770788477" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis" xlink:to="us-gaap_AvailableForSaleSecuritiesDebtSecurities_638185678770788477" order="3" use="optional" weight="1" />
  </calculationLink>
  <calculationLink xlink:role="http://www.harmonybiosciences.com/role/DisclosureInventoryDetails" xlink:type="extended" xlink:title="40601 - Disclosure - Inventory (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_InventoryNet" xlink:label="us-gaap_InventoryNet" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_InventoryGross" xlink:label="us-gaap_InventoryGross_638185678770788477" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_InventoryNet" xlink:to="us-gaap_InventoryGross_638185678770788477" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_InventoryRawMaterials" xlink:label="us-gaap_InventoryRawMaterials_638185678770798480" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_InventoryGross_638185678770788477" xlink:to="us-gaap_InventoryRawMaterials_638185678770798480" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_InventoryWorkInProcess" xlink:label="us-gaap_InventoryWorkInProcess_638185678770798480" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_InventoryGross_638185678770788477" xlink:to="us-gaap_InventoryWorkInProcess_638185678770798480" order="2" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_InventoryFinishedGoods" xlink:label="us-gaap_InventoryFinishedGoods_638185678770798480" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_InventoryGross_638185678770788477" xlink:to="us-gaap_InventoryFinishedGoods_638185678770798480" order="3" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_InventoryValuationReserves" xlink:label="us-gaap_InventoryValuationReserves_638185678770798480" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_InventoryNet" xlink:to="us-gaap_InventoryValuationReserves_638185678770798480" order="2" use="optional" weight="-1" priority="2" />
  </calculationLink>
  <calculationLink xlink:role="http://www.harmonybiosciences.com/role/DisclosureIntangibleAssetsScheduleOfExpectedFutureAnnualAmortizationExpenseForUnamortizedIntangibleAssetsDetails" xlink:type="extended" xlink:title="40702 - Disclosure - Intangible Assets - Schedule of Expected Future Annual Amortization Expense for Unamortized Intangible Assets (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_FiniteLivedIntangibleAssetsNet" xlink:label="us-gaap_FiniteLivedIntangibleAssetsNet" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseRemainderOfFiscalYear" xlink:label="us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseRemainderOfFiscalYear_638185678770798480" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_FiniteLivedIntangibleAssetsNet" xlink:to="us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseRemainderOfFiscalYear_638185678770798480" order="1" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseNextTwelveMonths" xlink:label="us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseNextTwelveMonths_638185678770798480" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_FiniteLivedIntangibleAssetsNet" xlink:to="us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseNextTwelveMonths_638185678770798480" order="2" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearTwo" xlink:label="us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearTwo_638185678770798480" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_FiniteLivedIntangibleAssetsNet" xlink:to="us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearTwo_638185678770798480" order="3" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearThree" xlink:label="us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearThree_638185678770798480" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_FiniteLivedIntangibleAssetsNet" xlink:to="us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearThree_638185678770798480" order="4" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearFour" xlink:label="us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearFour_638185678770808478" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_FiniteLivedIntangibleAssetsNet" xlink:to="us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearFour_638185678770808478" order="5" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="hrmy-20230331.xsd#hrmy_FiniteLivedIntangibleAssetExpectedAmortizationAfterYearFour" xlink:label="hrmy_FiniteLivedIntangibleAssetExpectedAmortizationAfterYearFour_638185678770808478" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_FiniteLivedIntangibleAssetsNet" xlink:to="hrmy_FiniteLivedIntangibleAssetExpectedAmortizationAfterYearFour_638185678770808478" order="6" use="optional" weight="1" />
  </calculationLink>
  <calculationLink xlink:role="http://www.harmonybiosciences.com/role/DisclosureIntangibleAssetsScheduleOfGrossCarryingAmountAndNetBookValueOfIntangibleAssetsDetails" xlink:type="extended" xlink:title="40703 - Disclosure - Intangible Assets - Schedule of Gross Carrying Amount and Net Book Value of Intangible Assets (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_IntangibleAssetsNetExcludingGoodwill" xlink:label="us-gaap_IntangibleAssetsNetExcludingGoodwill" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_IntangibleAssetsGrossExcludingGoodwill" xlink:label="us-gaap_IntangibleAssetsGrossExcludingGoodwill_638185678770808478" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_IntangibleAssetsNetExcludingGoodwill" xlink:to="us-gaap_IntangibleAssetsGrossExcludingGoodwill_638185678770808478" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_FiniteLivedIntangibleAssetsAccumulatedAmortization" xlink:label="us-gaap_FiniteLivedIntangibleAssetsAccumulatedAmortization_638185678770808478" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_IntangibleAssetsNetExcludingGoodwill" xlink:to="us-gaap_FiniteLivedIntangibleAssetsAccumulatedAmortization_638185678770808478" order="2" use="optional" weight="-1" priority="2" />
  </calculationLink>
  <calculationLink xlink:role="http://www.harmonybiosciences.com/role/DisclosureDebtBalancesOfLongTermDebtNetDetailsCalc2" xlink:type="extended" xlink:title="40802 - Disclosure - Debt - Balances of Long-term Debt, Net (Details) calc 2" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LongTermDebt" xlink:label="us-gaap_LongTermDebt" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LongTermDebtCurrent" xlink:label="us-gaap_LongTermDebtCurrent_638185678770808478" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LongTermDebt" xlink:to="us-gaap_LongTermDebtCurrent_638185678770808478" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LongTermDebtNoncurrent" xlink:label="us-gaap_LongTermDebtNoncurrent_638185678770808478" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LongTermDebt" xlink:to="us-gaap_LongTermDebtNoncurrent_638185678770808478" order="2" use="optional" weight="1" priority="2" />
  </calculationLink>
  <calculationLink xlink:role="http://www.harmonybiosciences.com/role/DisclosureAccruedExpensesDetails" xlink:type="extended" xlink:title="40901 - Disclosure - Accrued Expenses (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AccruedLiabilitiesCurrent" xlink:label="us-gaap_AccruedLiabilitiesCurrent" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AccruedRoyaltiesCurrent" xlink:label="us-gaap_AccruedRoyaltiesCurrent_638185678770818477" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AccruedLiabilitiesCurrent" xlink:to="us-gaap_AccruedRoyaltiesCurrent_638185678770818477" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="hrmy-20230331.xsd#hrmy_AccruedRebatesAndOtherSalesDeductionsCurrent" xlink:label="hrmy_AccruedRebatesAndOtherSalesDeductionsCurrent_638185678770818477" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AccruedLiabilitiesCurrent" xlink:to="hrmy_AccruedRebatesAndOtherSalesDeductionsCurrent_638185678770818477" order="2" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_InterestPayableCurrent" xlink:label="us-gaap_InterestPayableCurrent_638185678770818477" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AccruedLiabilitiesCurrent" xlink:to="us-gaap_InterestPayableCurrent_638185678770818477" order="3" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AccruedMarketingCostsCurrent" xlink:label="us-gaap_AccruedMarketingCostsCurrent_638185678770818477" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AccruedLiabilitiesCurrent" xlink:to="us-gaap_AccruedMarketingCostsCurrent_638185678770818477" order="4" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="hrmy-20230331.xsd#hrmy_AccruedResearchAndDevelopmentCurrent" xlink:label="hrmy_AccruedResearchAndDevelopmentCurrent_638185678770818477" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AccruedLiabilitiesCurrent" xlink:to="hrmy_AccruedResearchAndDevelopmentCurrent_638185678770818477" order="5" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="hrmy-20230331.xsd#hrmy_AccruedProfessionalFeesConsultingAndOtherServices" xlink:label="hrmy_AccruedProfessionalFeesConsultingAndOtherServices_638185678770818477" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AccruedLiabilitiesCurrent" xlink:to="hrmy_AccruedProfessionalFeesConsultingAndOtherServices_638185678770818477" order="6" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_OtherAccruedLiabilitiesCurrent" xlink:label="us-gaap_OtherAccruedLiabilitiesCurrent_638185678770818477" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AccruedLiabilitiesCurrent" xlink:to="us-gaap_OtherAccruedLiabilitiesCurrent_638185678770818477" order="7" use="optional" weight="1" priority="2" />
  </calculationLink>
  <calculationLink xlink:role="http://www.harmonybiosciences.com/role/DisclosureLeasesFuturePaymentsDetailsCalc2" xlink:type="extended" xlink:title="40904 - Disclosure - LEASES - Future payments (Details) (Calc2)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_OperatingLeaseLiability" xlink:label="us-gaap_OperatingLeaseLiability_638185678770818477" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue" xlink:to="us-gaap_OperatingLeaseLiability_638185678770818477" order="1" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount_638185678770828478" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount_638185678770828478" order="2" use="optional" weight="1" />
  </calculationLink>
  <calculationLink xlink:role="http://www.harmonybiosciences.com/role/DisclosureDebtBalancesOfLongTermDebtNetDetails" xlink:type="extended" xlink:title="41002 - Disclosure - Debt - Balances of Long-term Debt, Net (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LongTermDebt" xlink:label="us-gaap_LongTermDebt" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DebtInstrumentCarryingAmount" xlink:label="us-gaap_DebtInstrumentCarryingAmount_638185678770828478" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LongTermDebt" xlink:to="us-gaap_DebtInstrumentCarryingAmount_638185678770828478" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="hrmy-20230331.xsd#hrmy_UnamortizedDebtDiscountAssociatedWithExitFeeDebtFinancingCostsAndDiscountWithWarrantFinancing" xlink:label="hrmy_UnamortizedDebtDiscountAssociatedWithExitFeeDebtFinancingCostsAndDiscountWithWarrantFinancing_638185678770828478" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LongTermDebt" xlink:to="hrmy_UnamortizedDebtDiscountAssociatedWithExitFeeDebtFinancingCostsAndDiscountWithWarrantFinancing_638185678770828478" order="2" use="optional" weight="-1" priority="2" />
  </calculationLink>
  <calculationLink xlink:role="http://www.harmonybiosciences.com/role/DisclosureDebtFutureMinimumPaymentsDetails" xlink:type="extended" xlink:title="41003 - Disclosure - Debt - Future Minimum Payments (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DebtInstrumentCarryingAmount" xlink:label="us-gaap_DebtInstrumentCarryingAmount" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalRemainderOfFiscalYear" xlink:label="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalRemainderOfFiscalYear_638185678770828478" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_DebtInstrumentCarryingAmount" xlink:to="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalRemainderOfFiscalYear_638185678770828478" order="1" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInNextTwelveMonths" xlink:label="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInNextTwelveMonths_638185678770828478" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_DebtInstrumentCarryingAmount" xlink:to="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInNextTwelveMonths_638185678770828478" order="2" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearTwo" xlink:label="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearTwo_638185678770828478" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_DebtInstrumentCarryingAmount" xlink:to="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearTwo_638185678770828478" order="3" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearThree" xlink:label="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearThree_638185678770828478" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_DebtInstrumentCarryingAmount" xlink:to="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearThree_638185678770828478" order="4" use="optional" weight="1" />
  </calculationLink>
  <calculationLink xlink:role="http://www.harmonybiosciences.com/role/DisclosureDebtInterestExpenseDetails" xlink:type="extended" xlink:title="41004 - Disclosure - Debt - Interest Expense (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_InterestExpenseDebt" xlink:label="us-gaap_InterestExpenseDebt" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_InterestExpenseDebtExcludingAmortization" xlink:label="us-gaap_InterestExpenseDebtExcludingAmortization_638185678770838483" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_InterestExpenseDebt" xlink:to="us-gaap_InterestExpenseDebtExcludingAmortization_638185678770838483" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AmortizationOfFinancingCosts" xlink:label="us-gaap_AmortizationOfFinancingCosts_638185678770838483" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_InterestExpenseDebt" xlink:to="us-gaap_AmortizationOfFinancingCosts_638185678770838483" order="2" use="optional" weight="1" priority="2" />
  </calculationLink>
  <calculationLink xlink:role="http://www.harmonybiosciences.com/role/DisclosureLeasesSupplementalBalanceSheetInformationDetails" xlink:type="extended" xlink:title="41102 - Disclosure - Leases - Supplemental Balance Sheet Information (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_OperatingLeaseLiability" xlink:label="us-gaap_OperatingLeaseLiability_2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_OperatingLeaseLiabilityCurrent" xlink:label="us-gaap_OperatingLeaseLiabilityCurrent_638185678770838483" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_OperatingLeaseLiability_2" xlink:to="us-gaap_OperatingLeaseLiabilityCurrent_638185678770838483" order="1" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_OperatingLeaseLiabilityNoncurrent" xlink:label="us-gaap_OperatingLeaseLiabilityNoncurrent_638185678770838483" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_OperatingLeaseLiability_2" xlink:to="us-gaap_OperatingLeaseLiabilityNoncurrent_638185678770838483" order="2" use="optional" weight="1" />
  </calculationLink>
  <calculationLink xlink:role="http://www.harmonybiosciences.com/role/DisclosureLeasesFuturePaymentsDetails" xlink:type="extended" xlink:title="41104 - Disclosure - Leases - Future Payments (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsRemainderOfFiscalYear" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityPaymentsRemainderOfFiscalYear_638185678770838483" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_1" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityPaymentsRemainderOfFiscalYear_638185678770838483" order="1" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths_638185678770838483" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_1" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths_638185678770838483" order="2" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo_638185678770848484" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_1" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo_638185678770848484" order="3" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree_638185678770848484" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_1" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree_638185678770848484" order="4" use="optional" weight="1" />
  </calculationLink>
  <calculationLink xlink:role="http://www.harmonybiosciences.com/role/DisclosureIncomeTaxesScheduleOfDifferenceBetweenStatutoryFederalIncomeTaxRateDetails" xlink:type="extended" xlink:title="41601 - Disclosure - Income Taxes - Schedule of Difference Between Statutory Federal Income Tax Rate (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_EffectiveIncomeTaxRateContinuingOperations" xlink:label="us-gaap_EffectiveIncomeTaxRateContinuingOperations_637684186483472492" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_EffectiveIncomeTaxRateReconciliationAtFederalStatutoryIncomeTaxRate" xlink:label="us-gaap_EffectiveIncomeTaxRateReconciliationAtFederalStatutoryIncomeTaxRate_638185678770848484" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_EffectiveIncomeTaxRateContinuingOperations_637684186483472492" xlink:to="us-gaap_EffectiveIncomeTaxRateReconciliationAtFederalStatutoryIncomeTaxRate_638185678770848484" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_EffectiveIncomeTaxRateReconciliationStateAndLocalIncomeTaxes" xlink:label="us-gaap_EffectiveIncomeTaxRateReconciliationStateAndLocalIncomeTaxes_638185678770848484" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_EffectiveIncomeTaxRateContinuingOperations_637684186483472492" xlink:to="us-gaap_EffectiveIncomeTaxRateReconciliationStateAndLocalIncomeTaxes_638185678770848484" order="2" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_EffectiveIncomeTaxRateReconciliationTaxCredits" xlink:label="us-gaap_EffectiveIncomeTaxRateReconciliationTaxCredits_638185678770848484" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_EffectiveIncomeTaxRateContinuingOperations_637684186483472492" xlink:to="us-gaap_EffectiveIncomeTaxRateReconciliationTaxCredits_638185678770848484" order="3" use="optional" weight="-1" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_EffectiveIncomeTaxRateReconciliationOtherAdjustments" xlink:label="us-gaap_EffectiveIncomeTaxRateReconciliationOtherAdjustments_638185678770848484" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_EffectiveIncomeTaxRateContinuingOperations_637684186483472492" xlink:to="us-gaap_EffectiveIncomeTaxRateReconciliationOtherAdjustments_638185678770848484" order="4" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_EffectiveIncomeTaxRateReconciliationChangeInDeferredTaxAssetsValuationAllowance" xlink:label="us-gaap_EffectiveIncomeTaxRateReconciliationChangeInDeferredTaxAssetsValuationAllowance_638185678770848484" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_EffectiveIncomeTaxRateContinuingOperations_637684186483472492" xlink:to="us-gaap_EffectiveIncomeTaxRateReconciliationChangeInDeferredTaxAssetsValuationAllowance_638185678770848484" order="5" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_EffectiveIncomeTaxRateReconciliationShareBasedCompensationExcessTaxBenefitPercent" xlink:label="us-gaap_EffectiveIncomeTaxRateReconciliationShareBasedCompensationExcessTaxBenefitPercent_638185678770848484" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_EffectiveIncomeTaxRateContinuingOperations_637684186483472492" xlink:to="us-gaap_EffectiveIncomeTaxRateReconciliationShareBasedCompensationExcessTaxBenefitPercent_638185678770848484" order="6" use="optional" weight="1" />
  </calculationLink>
</link:linkbase>
