No slowing of approval train at FDA

Despite major challenges and demands created by the coronavirus pandemic, FDA maintained a steady pace in 2021 in approving important new therapies for market entry, including new vaccines and treatments for Covid-19. Last year saw the Center for Drug Evaluation and Research (CDER) approve 50 new molecular entities (NMEs), many benefitting from priority and accelerated review timelines. In addition, the Center for Biologics Evaluation and Research (CBER) approved several vaccines and cellular products to further expand the new medicines list.

The CDER total is slightly less than the 53 novel drugs brought to market in 2020 and the 2018 record total of 59 innovative therapies. As in recent years, a majority of the new products received orphan drug status, and 15 had indications to treat cancer. More than half moved forward through expedited procedures, 14 benefitting from accelerated approvals and 32 granted priority reviews. Continued requests for faster vetting requires additional involvement of CDER experts to provide R&D advice and to meet tighter deadlines, which agency officials say cannot be sustained without additional review staff and resources.

Despite similar pressures, CBER approved 10 biologics license applications (BLAs), notably one granting full approval for Pfizer/BioNTech’s Comirnaty vaccine. Some analysts include only about half of these in combined lists of FDA’s new NMEs, notably new vaccines for hepatitis B virus and for tick-borne encephalitis, and therapies for myeloma and lymphoma.

Probably the most discussed new drug is Biogen’s Aduhelm for Alzheimer’s disease, which CDER okayed for market despite limited evidence of its efficacy and a thumbs-down on approval from its advisory committee. FDA reviewers, however, decided its benefits outweighed risks, as no other treatment is approved for this very serious condition.

Other notable new therapies from CDER include treatments for myasthenia gravis, lupus, Pompe disease, severe asthma, sickle cell disease, to prevent dwarfism in children and to manage very high cholesterol. Lung cancer, endometrial cancer and leukemia gained added treatment options, as did transplant patients.

The lists, moreover, do not include those innovative Covid therapies and vaccines granted emergency use authorizations (EUAs). In December, FDA authorized two notable oral medications to treat early Covid infections—Pfizer’s Paxlovid and Molnupiravir from Merck and Ridgeback Biotherapeutics—providing a more accessible alternative to antivirals that require infusion in a clinic or doctors’ office.

More inspection delays

Analysts note that several additional new products failed to gain approval in 2021, due to FDA’s inability to conduct necessary inspections of certain manufacturing sites. That situation is unlikely to change any time soon, as the agency has once again pulled back on inspectional activities due to the spread of the Covid omicron variant.

Last July, FDA revived efforts to ramp up inspections of domestic production facilities, an effort that made a notable dent in the agency’s sizable inspection backlog for medical products. The hope was to visit most of the 3,000 sites in need of oversight in 2022 and also to test a new program to enhance foreign inspection operations.

These goals were put on hold with the agency’s announcement this week that it would continue only mission-critical inspections through Jan. 19, and postpone most other inspectional activities, including foreign site visits. Also delayed is the planning effort set to begin in February for revising foreign inspection assignments in an effort to address challenges in staffing overseas offices and rebuilding the cadre of US-based inspectors willing to travel to foreign drug production sites.

Meanwhile, FDA will continue to use remote tools to maintain oversight of foods, drugs, medical products and tobacco at home and abroad.

— Jill Wechsler, Washington Correspondent for MJH Life Sciences’ pharma sciences brands