The industry is adjusting to the pandemic, but FDA approvals could dip this year. Several new drugs for atopic dermatitis may get the agency’s green light.
Like so much else in healthcare and beyond, a large question hangs over drug development in 2021 and the pace of FDA approvals: How much of an effect will COVID-19 have?
Because the majority of FDA approvals in the latter part of 2020 were based on results of trials conducted before the pandemic, the full impact of the pandemic on approvals may not become evident till this year. When the pandemic reached the United States in March and lockdowns throughout the country began, some active trials paused, many trials set to start were delayed, and new COVID-19-focused trials commenced. In just March and April, 905 clinical trials were suspended as a result of the pandemic, according to a study published in the September 2020 issue of Annals of Surgery. Meanwhile, a slew of others were rapidly launched to assess potential COVID-19 vaccines and treatments.
Between 20% and 25% of trials suspended enrollment as a result of the pandemic, according to Kenneth Getz, MBA, the deputy director of the Tufts Center for the Study of Drug Development in Boston. But Getz says that following delays of four to six months, most of those trials have now resumed as trial investigators adapted to using more remote or virtual methods. Approximately one-third of ongoing clinical trials started moving to a remote model very soon after the pandemic hit, but almost half (45%) continued following the original protocol approach, with patients coming into trial centers for visits, says Getz. Most of the trials that stuck with in-person visits were testing drugs for serious diseases such as cancer.
Getz says institutional review boards, ethical review committees and regulatory agencies deserve credit for helping with recruitment by allowing for some adjustments to trial design. Although some delays in getting the studies underway were inevitable, anecdotal reports suggest that once people were enrolled in a trial, they stayed enrolled, says Getz.
It remains to be seen how new, more virtual trial models will affect collection and reporting, says Getz. While conducting trials with more remote checks and monitoring makes participation more convenient for study volunteers and may reduce the number of dropouts, recruitment amid the pandemic is likely to be a struggle.
“A lot more people are more aware of clinical trials, but they think that participation may be riskier or less safe, especially if there might be some exposure to the coronavirus if they’re involved in a hybrid study that involves some in-person visits as well as some at-home visits,” says Getz.
Another worry of drug developers is whether the FDA is so focused on COVID-19 vaccines and treatments that review of other drugs will languish, notwithstanding Prescription Drug User Fee Act timelines. Drug developers and others are concerned that the agency is spread too thin and, as a result, fewer drugs will be reviewed and approved.
Aducanumab’s fate to be determined
Aside from additional COVID-19 vaccines, perhaps the most anticipated (and possibly most controversial) approval decision this year concerns aducanumab, a monoclonal antibody developed by Biogen and Eisai Co. Ltd., a Japanese company, as a treatment for Alzheimer’s disease. Current treatments for Alzheimer’s are only modestly effective, and recent attempts to find better ones have foundered in late-stage trials. With baby boomers entering old age, the market for an effective drug for Alzheimer’s disease would be enormous.
Aducanumab looked like it was going to join the long list of failures when Biogen and Eisai said in early 2019 early that they were shelving the drug after negative results from in two trials. Later that year, though, they reversed course and said further analysis suggested efficacy.
The agency seems to agree with the companies, judging by a document that became public late last year. But a watchdog group, Public Citizen, accused the agency of “inappropriately close collaboration” with the drug’s developers. Days after the positive FDA assessment, the up-and-down prospects of aducanumab took a downturn when an advisory committee of outside experts voted overwhelmingly against approval. Aimee Tharaldson, Pharm.D., senior clinical pharmacist of Emerging Therapeutics at Express Scripts, says she believes that approval is unlikely. A final decision is expected by March, but the schedule may hinge on the timing of President-elect Joe Biden’s selection of an FDA commissioner and the Senate confirmation needed for that person to assume the top post at the agency.
Atoptic dermatitis drugs in the offing
Another therapeutic area to keep an eye out for in the coming year is atopic dermatitis, the most common type of eczema. There are drugs in late-stage clinical development for moderate-to-severe atopic dermatitis.
Several of these drugs are Janus kinase (JAK) inhibitors, a type of disease-modifying antirheumatic drug. Pfizer’s abrocitinib seems headed for approval by April. AbbVie’s JAK inhibitor, Rinvoq (upadacitinib), which is currently approved as a treatment for rheumatoid arthritis, is expected to get an added indication for atopic dermatitis by June. Eli Lilly and Company’s Olumiant (baricitinib) may also be approved for atopic dermatitis this year. In November 2020, the FDA issued an emergency use authorization for a combination of Olumiant and remdesivir as a treatment for COVID-19. In addition, Leo Pharma’s tralokinumab, a novel treatment given as subcutaneous injection every two weeks, is expected to be approved this year as a treatment for atopic dermatitis.
CAR-T for multiple myeloma?
Chimeric antigen receptor (CAR)T-cell therapy involves taking a patient’s T cells, altering them in a laboratory so they attack cancer cells and then reinfusing them. Currently approved as a treatment for acute lymphoblastic leukemia and several different types of lymphoma, CAR-T treatment is edging its way into the mainstream and may be approved for multiple myeloma this year. Researchers presented positive results for two CAR-T trials for the blood cancer last month at the annual meeting of the American Society of Hematology (ASH). Janssen’s ciltacabtagene autoleucel, which is expected to be approved in the second half of the year, showed a near perfect (97%) overall response rate over 12.4 months in patients whose disease had worsened after multiple treatments. At a median follow-up of 12.4 months, the median length of response and progression-free survival endpoints were not reached.
Bristol Myers Squibb and Bluebird bio’s CAR-T therapy, idecabtagene vicleucel, is expected to be approved in March as a treatment for multiple myeloma. Results of a phase 1 trial, which came out ahead of the ASH meeting but were also presented there, showed a response rate of 76% and a complete response rate (no detectable cancer after treatment) of 39%. The median length of response was 10.3 months.
Rare disease treatments
Also in the offing this year are possible approvals for treatments for two rare diseases.
Orphazyme’s arimoclomol is an HSF1 stimulant pending approval for the treatment of Niemann-Pick disease type C, a rare, progressive lysosomal storage disorder that affects approximately 200 people in the U.S. With no approved treatments for the disease, most patients die by age 40. An FDA decision on the treatment is expected March 21.
PTC Therapeutics’ eladocagene exuparvovec is a gene therapy for the treatment of aromatic L-amino acid decarboxylase deficiency, which has been identified in approximately 100 patients in the U.S. The one-time infusion is expected to be priced somewhere between
$2 and $3 million.
Jaime Rosenberg is a freelance writer based in Jersey City, New Jersey.