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CASE STUDY: Mytesi


One of Johns Hopkins University First Female Scientists

  • First botanical drug approved by the US FDA for treating diarrheal caused by HIV/AIDS antiretroviral therapy

  • Delayed-release oral tablet containing 125 mg Crofelemer​, a botanical drug substance derived from the crude plant latex of Croton lechleri (Dragon’s Blood)

Structure

  • An oligomeric proanthocyanidin mixture primarily composed of (+)-catechin, (-)-epicatechin, (+)-gallocatechin, and (-)-epigallocatechin monomer units linked in random sequence​

  • Multiple analytical methods collectively provide extensive information on the structural signatures of Crofelemer (e.g., the composition of proanthocyanidin oligomers)


Therapeutic Consistency

  • Botanical raw material control

    • Implementation of Good Agricultural and Collection Practices (GACP)

    • Restriction of harvesting botanical raw material to specific ecogeographic regions (EGRs)

    • Reduces the variability at the plant and raw material levels

  • Bioassay

    • based on well-known mechanism of action (i.e., crofelemer targets and controls dual intestinal chloride channels: cAMP-stimulated cystic fibrosis transmembrane conductance regulator Cl – channel and the calcium-activated Cl – channel)

    • Potentially provides more flexibility for the manufacturer to make post approval changes (e.g., expansion of EGRs to increase and diversify the botanical raw material supply)


Dose Response

Dose-response clinical data is generated based on multiple batches

  • The drug’s effects were not sensitive to the tested doses in a range of 125 – 500 mg bid

  • The estimated drug concentrations in the GI tract after oral dosing of 125 mg bid are several-fold higher than the concentrations used to saturate the targeted chloride ion channels

  • Multiple batch data did not reveal noticeable clinical differences among drug product batches manufactured from different drug substance batches

  • Natural variations observed in crofelemer were unlikely to have a significant impact on the efficacy of Fulyzaq

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