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  • 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)


  •  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

A showcase of the first botanical drug approved by the US FDA for treating diarrheal caused by HIV/AIDS antiretroviral therapy, about the what was described for the structure, methods to test and ensure therapeutic consistency, studies of dose response. This set an example for future botanical drug development.
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