FDA Updates: Brilinta’s Priority Review in Stroke; Biogen’s Alzheimer’s BLA; Mytesi IND in Cancer Care

Biogen, AstraZeneca, and Jaguar Health each announced regulatory milestones with FDA this week, as action before the agency picks up steam.

Biogen announced it completed submission of a Biologics License Application (BLA) for aducanumab, a monoclonal antibody to treat Alzheimer’s disease. The drug targets amyloid plaques in the brain, and the application is based on results from two phase trials, EMERGE and ENGAGE, involving patients with mild cognitive impairment due to early stage Alzheimer’s. According to Biogen’s July 8 statement, patients in EMERGE showed significant slowing of decline in both measures of cognitive function and activities of daily living, with results most consistent among patients taking high doses. ENGAGE did not meet its primary endpoint, but, “Biogen believes a subset of data from ENGAGE are supportive of the outcome in EMERGE.”

Trials for the drug were halted in May 2019 but Biogen then reversed course in October, citing data from patients taking the higher doses. The shift drew criticism, but FDA may still approve the treatment, as the Alzheimer’s population is growing, and no new therapy has been approved for the disease in 17 years.

AstraZeneca announced July 9 that FDA had accepted its supplemental New Drug Application (sNDA) for Brilinta (ticagrelor) to reduce the risk of subsequent stroke in those patients who have already experienced an acute ischemic stroke or transient ischemic attack, known as a TIA. If approved, Brilinta plus aspirin would be the first FDA-approved dual antiplatelet therapy in this indication. According to the Mayo Clinic, TIA is the most common type of stroke, and 1 in 3 patients who has one will go on to have a stroke—half of these patients are at risk of having the stroke within a year.

According to a company statement, the sNDA was based on findings from the phase 3 THALES trial, which showed that the 90 mg dose of Brilinta with aspirin, used twice daily for 30 days, brought meaningful reduction in the combined endpoint of stroke and death, compared with taking aspiring alone. Full data from THALES will be presented at an upcoming scientific meeting. FDA action on this indication is scheduled for the fourth quarter of 2020.

Brilinta is currently approved to reduce the risk of cardiovascular death, myocardial infarction, and stroke in patients with acute coronary syndrome or a history of myocardial infarction (heart attack). It is also used for patients who have received a stent for ACS to reduce the risk of stent thrombosis, and to prevent heart attacks and strokes in patients with coronary artery disease.

Jaguar Health on July 6 announced that its subsidiary, Napo Pharmaceuticals, filed an investigational new drug (IND) application for Mytesi (crofelemer) to relief diarrhea for caused by cancer treatment. The non-opiate, plant-based chloride ion channel modulating antidiarrheal treatment, is currently used to bring relief to adult patients with HIV/AIDS who are on antiretroviral therapy. In a statement, Jaguar Health said that crofelemer, the active ingredient, “comes from the Croton lechleri tree, which his responsibly and sustainably harvested in South America.”

The problem of patients receiving targeted therapy for cancer being unable to tolerate doses or complete therapy due to toxicity is significant. For example, data from the MURANO study, presented in May at the American Society of Clinical Oncology, showed that patients who stopped Venclexta with rituximab early, often due to toxicity, had worse outcomes than those whose physicians managed the toxicity with dosing schedules.

"Many cancer patients on targeted therapy require drug holidays or dose reductions in their therapy due to diarrhea," Lisa Conte, Jaguar's president and CEO, said in a statement. "Reducing frequency of watery stools will provide symptomatic relief of diarrhea and should allow better adherence to the therapeutic dosing of any targeted therapies, potentially leading to better clinical outcomes.”