Emergency Use Authorization (EUA) for molnupiravir
On November 30, 2021, FDA’s Antimicrobial Drug Advisory Committee (ADAC) met to discuss an Emergency Use Authorization (EUA) for Merck/Ridgeback’s molnupiravir for the treatment of mild to moderate COVID-19 in adult patients at high risk of progression to severe COVID-19. The committee voted 13 to 10 in support of the EUA. While the panelists agreed that more studies are required to better characterize molnupiravir, the members that voted ‘yes’ generally highlighted the unmet need for additional treatment options. The ‘no’ voters were concerned about the safety risks of the therapy combined with its modest efficacy. Safety issues include embryofetal toxicity and effects on bone formation and cartilage development (based on animal studies), as well as the possibility of the drug driving COVID-19 variants. The FDA now will consider the panel’s recommendations and likely will make a decision on the EUA application within the coming weeks.
The “Oral Antivirals in Development for COVID-19” issues document has been updated to include the above information.
Fyarro Approved
The U.S. Food and Drug Administration (FDA) approved Fyarro™ (sirolimus protein-bound particles for injectable suspension – Aadi Bioscience) on Nov. 22, 2021. It is a nanoparticle albumin-bound (nab) formulation of the mammalian target of rapamycin (mTOR) inhibitor, sirolimus (also called rapamycin). Its indication is for treating adults who have metastatic or locally advanced malignant perivascular epithelioid-cell tumors (PEComas). An extremely rare kind of soft-tissue sarcoma, cancerous PEComas are believed to affect only a few hundred patients each year in the U.S. Although they can occur in any body organ, most malignant PEComas are found in the abdominal cavity, with about one-quarter of cases involving the female reproductive tract. Typically, they are diagnosed mostly in middle-aged adults. Surgical removal of tumors and surrounding tissue is the standard of care. Chemotherapy (chemo) and radiation are not very effective for PEComas. Fyarro is the first drug specifically indicated to treat them. Its recommended dosing is 100mg/m2 infused intravenously (IV) on the first and eighth days of 21-day treatment cycles. In a clinical study, 12 of the 31 participants who used Fyarro responded to treatment. Within that group, response lasted two years or longer for seven of them. Patients receiving it may experience hypersensitivity reactions, so they should be observed after each treatment. A wide range of other possibly serious adverse effects include reduced bone marrow activity, low potassium levels, elevated blood glucose, gastrointestinal (GI) hemorrhaging and sores in the mouth. Aadi will launch Fyarro in the first quarter of 2022; distribution plans are not yet known. The estimated annual wholesale acquisition cost (WAC) for Fyarro is $468,000.
Clozapine Risk Evaluation and Mitigation Strategy Temporarily Suspended
After changes were made in clozapine’s Risk Evaluation and Mitigation Strategy (REMS) on Nov. 15, 2021, some providers are unable to complete required documentation and some patients are having trouble getting their prescriptions filled. Clozapine is an antipsychotic drug used to treat schizophrenia and schizoaffective disorder. It should not be stopped suddenly. To help assure that patients have continued access to clozapine, the FDA has removed REMS requirements for wholesalers and pharmacies until necessary paperwork can be processed.