The FDA Issues Complete Response Letter for Fasenra

The FDA has issued a complete response letter (CRL) regarding the supplemental biologics license application (sBLA) for Fasenra (benralizumab) for patients with inadequately controlled chronic rhinosinusitis with nasal polyps.

The sBLA submitted to the FDA by included data from the OSTRO phase 3 trial, which met both co-primary endpoints with a safety profile consistent with the known profile of the medicine, according to the company. The CRL requested additional clinical data and the company is working closely with the FDA regarding next steps. AstraZeneca is conducting a second phase 3 trial, ORCHID, in this indication.

Fasenra is a monoclonal antibody that binds directly to IL-5 receptor alpha on eosinophils and attracts natural killer cells to induce depletion of blood and tissue eosinophils. It is currently approved as an add-on maintenance treatment for severe eosinophilic asthma in the United States, the European Union, Japan, and other countries.

The FDA had granted orphan drug designation for Fasenra for eosinophilic granulomatosis with polyangiitis in 2018, and hyper-eosinophilic syndrome and eosinophilic esophagitis in 2019. In November 2021, the FDA also granted orphan status for Fasenra for eosinophilic gastroenteritis and eosinophilic gastritis, and a fast-track designation for the treatment of eosinophilic gastritis in the United States.

Men are more likely to be diagnosed with this condition, but women are more likely to have more serious disease, according to a one study. The age at diagnosis ranges from 40 to 60. Chronic rhinosinusitis with nasal polyps can cause sinus pain and nose stuffiness to loss of smell. The polyps result from inflammation in the lining of the nose. This condition can be difficult to treat and recurrences are frequent. It can occur in patients who also have asthma.

The FDA approved the first treatment for chronic rhinosinusitis with nasal polyps in 2019. Dupixent (dupilumab), developed jointly by Sanofi and Regeneron. It is fully-human monoclonal antibody that inhibits the signaling of interleukin-4 (IL-4) and interleukin-13 (IL-13), two proteins that play a central role in type 2 inflammation. Data from Dupixent clinical trials have shown that inhibiting IL-4 and IL-13 helps address the inflammation that plays a major role in chronic rhinosinusitis with nasal polyps, asthma, and atopic dermatitis.

Additionally, the FDA approved GlaxoSmithKline’s Nucala (mepolizumab) in July 2021 for this same indication. Nucala targets IL-5, which is believed to work by preventing IL-5 from binding to its receptor on the surface of eosinophils, reducing blood eosinophils and maintaining them within normal levels.