Expected FDA Approvals for 2021 Include Drugs for Alzheimer Disease, Atopic Dermatitis

Although therapeutics and vaccines for COVID-19 have dominated the news in the last year, development of other drugs has continued.

A new report from OptumRx has outlined 5 expected drug approvals from the FDA, including a first-in-class disease modifying treatment for Alzheimer disease, a treatment for paroxysmal nocturnal hemoglobinuria (PNH), and 3 treatments for atopic dermatitis.

Although therapeutics and vaccines for COVID-19 have dominated the news in the past year, development of other drugs has continued, according to the report. The number of novel FDA approvals could approach a new record high in 2021, following the second highest number recorded in 2020 with 53 new approvals.

These new approvals could include aducanumab for Alzheimer disease, pegcetacoplan for the rare disease PNH, and 3 drugs for patients with moderate-to-severe atopic dermatitis: abrocitinib, tralokinumab, and ruxolitinib topical cream. All 5 drugs have anticipated approval dates between May and September 2021.

Aducanumab is a human monoclonal antibody in development for the treatment of Alzheimer disease. Several prescription drugs are approved to treat the symptoms of Alzheimer, although if aducanumab were approved it would be a first-in-class disease modifying treatment. It works by reducing amyloid plaques in the brain.

Aducanumab has been evaluated in 2 trials with patients with mild cognitive impairment due to Alzheimer disease and mild Alzheimer disease. In March 2019, the trials were stopped by an independent data monitoring committee, which found that they were unlikely to meet their primary endpoint, although Biogen announced that it would still pursue an FDA filing based on a new analysis.

In November 2020, an FDA Advisory Committee met to discuss the safety and efficacy of aducanumab, and they voted not to endorse the treatment. However, the FDA extended the review period for the drug by 3 months in January 2021, and a decision is now expected in June 2021. The report noted that the FDA is not bound by the Advisory Committee’s vote and it is still possible that officials could accept the application.

Several questions remain about aducanumab, including the fact that it only demonstrated a statistically significant improvement in 1 of the 2 pivotal trials. The improvements demonstrated in the positive trial were small and questions remain about the clinical significance. These and other trial results have raised questions about whether amyloid is the correct target for Alzheimer disease treatments, according to the report. Aducanumab was also associated with adverse effects (AEs), including brain swelling.

Pegcetacoplan is in development for the treatment of adults with PNH, a rare disease that causes the immune system to attack and break down healthy red blood cells, leading to anemia. Symptoms can include fatigue, jaundice, hemoglobin in the urine, and difficulty breathing, and thrombosis occurs in 15% to 30% of patients. Just 400 to 500 cases of PNH are diagnosed in the United States each year, mostly among people in their 30s and 40s.

Pegcetacoplan is designed to regulate excessive activation of the complement cascade. Its efficacy was evaluated against eculizumab, a comparable type of inhibitor currently used for PNH, in the phase 3 PEGASUS trial. Pegcetacoplan was found to be superior, with a difference of 3.8 g/dL compared to eculizumab. Furthermore, 85% of pegcetacoplan-treated patients were transfusion-free over 16 weeks compared to 15% of eculizumab-treated patients, according to the report.

If approved, pegcetacoplan would be the first PNH therapy to target a different portion of the complement cascade from eculizumab or ravulizumab, another competitor approved for the treatment of PNH. It is administered via subcutaneous injection and is dosed twice a week. In clinical trials, it was associated with higher rates of AEs, such as diarrhea and injection site reactions. It has an expected FDA decision in May 2021, according to the report.

The other 3 drugs in the report are all for the treatment of atopic dermatitis. Symptoms can include skin dryness and extreme itchiness and can lead to repeated scratching. Atopic dermatitis is characterized by unpredictable flare-ups that disrupt the daily life of patients and their families, which makes disease management complex and frustrating, according to the report.

Abrocitinib is a kinase inhibitor, which would be indicated to treat moderate-to-severe atopic dermatitis in patients aged 12 years and older. It is a Janus kinase (JAK) inhibitor, meaning it inhibits the autoimmune process and helps ease inflammation and other related symptoms. In particular, the report said abrocitinib selectively inhibitors JAK1, which is believed to be specifically involved in causing the symptoms of atopic dermatitis. Experts expect an FDA approval in the third quarter of 2021.

Tralokinumab is intended to treat adults with moderate-to-severe atopic dermatitis. It acts on interleukin-13, which plays a key role in the underlying chronic inflammation in atopic dermatitis. If approved, it would offer a novel mechanism of action for this disease and would be administered subcutaneously every 2 weeks or every 4 weeks, with or without a topical corticosteroid. It has an expected FDA decision in April 2021.

Finally, ruxolitinib topical cream is in development for mild-to-moderate atopic dermatitis in patients aged 12 years and older. It is available as an oral brand for the treatment of myelofibrosis, polycythemia vera, and graft-versus-host disease. As the topical formulation, it is a selective JAK inhibitor that directly targets 2 chemical pathways that underlie atopic dermatitis. By disrupting both JAK1 and JAK2, the report said it helps to limit symptoms of atopic dermatitis. An FDA decision is anticipated in June 2021.

REFERENCE

OptumRx Drug Pipeline Insights Report. OptumRx; 2021. https://www.optum.com/content/dam/optum3/optum/en/resources/PDFs/orx3418657-210405-b2b-drug_pipeline-report_2021-q1-finalv1.pdf. Accessed April 28, 2021.