FDA Decisions Expected this Week for Five Products

The FDA has a busy week ahead, with Prescription Drug User Fee Act (PDUFA) action dates at the end of this week for five products.

The first expected decision is Bristol Myers Squibb’s mavacamten, which is being reviewed to treat obstructive hypertrophic cardiomyopathy, a progressive disease in which excessive contraction of the heart muscle and reduced ability of the left ventricle to fill can lead to the development of cardiac dysfunction.

Mavacamten is a first-in-class therapy that treats the treat the underlying cause of hypertrophic cardiomyopathy. It addresses the excessive contraction of the heart that leads to severe disease where the blood flow is obstructed.

The FDA’s original PDUFA date was January 28, 2022, but in November 2021, the regulatory agency extended the date to April 28, 2022, to review information about the proposed Risk Evaluation Mitigation Strategy (REMS). No new data or studies were requested.

The new drug application was supported by data from the EXPLORER-HCM phase 3 clinical trial, which enrolled 251 patients. Results from the trial showed that mavacamten demonstrated a robust treatment effect with clinically meaningful improvements in symptoms, functional status, and quality of life, as well as the ability to relieve left ventricular obstruction. Investigators found that all primary and secondary endpoints were met. The data were published in The Lancet in August 2020.

But while the therapy provides benefit, mavacamten would have to be priced below $15,000 per year to reach common thresholds for cost-effectiveness, according to the final report from the Institute for Clinical and Economic Review (ICER).

ICER reviewers also had concerns about long-term safety and an independent appraisal committee indicated that the evidence is not adequate to demonstrate a net health benefit of mavacamten added to background therapy.

Investigators from ICER compared mavacamten with Pfizer’s Norpace (disopyramide), which is an anti-arrhythmic drug approved for the treatment of arrhythmia, although it is used with patients who have obstructive hypertrophic cardiomyopathy who are not controlled with beta blockers or the calcium channel blocker verapamil.

“The evidence suggests that mavacamten may deliver important health benefits for patients with a lower rate of side effects than seen with some other medications for HCM, but clinical experts differ in their opinions about the long-term clinical implications of mavacamten reducing left ventricular ejection fraction in some patients. Additional safety data are needed to resolve these issues,” David Rind, M.D., ICER’s chief medical officer, said in a press release.

Qelbree for ADHD in adults

On Friday, April 29, 2022, a decision is expected on the supplemental new drug application for Qelbree (viloxazine) to treat adults with attention-deficit hyperactivity disorder (ADHD). It was approved in April 2021 to children 6 to 17 years of age.

Developed by Supernus Pharmaceuticals, Qelbree’s applications for adult was supported by data from positive results in a phase 3 study. That trial showed that Qelbree at a daily dose of up to 600 mg met the primary endpoint in improving the symptoms of ADHD from baseline to end of study as measured by ADHD Investigator Symptom Rating Scale.

Qelbree, novel non-stimulant treatment for children with ADHD in a decade, was launched in the second quarter of 2021 and for the year, closed the year with 13,380 prescriptions written, according to the company.

Three decisions expected on Saturday April 30, 2022.

The first is Axsome Therapeutics’ meloxicam-rizatriptan (AXS-07) is novel therapy for the acute treatment of migraine. The FDA had accepted the company’s application in September 2021. Previously regulators were concerned that due to COVID-19 pandemic-related travel restrictions, they wouldn’t be able to complete a required inspection of a contract manufacturing facility. But Axsome officials said they’ve been notified that the FDA does not anticipate any issues with completing this facility inspection prior to the PDUFA date.

Meloxicam is a new molecular entity for migraine enabled by Axsome’s MoSEIC (Molecular Solubility Enhanced Inclusion Complex) technology, which results in rapid absorption of meloxicam while maintaining a long plasma half-life. Meloxicam is a COX-2 preferential non-steroidal anti-inflammatory drug and rizatriptan is a 5-HT1B/1D agonist.

A second expected decision on Saturday is for surufatinib for the treatment of patients with pancreatic and non-pancreatic neuroendocrine tumors (NETs). Developed by China-based Hutchmed, surufatinib, if approved would be the company’s first oncology therapy approved outside of China.

The FDA accepted the application in July 2021. The new drug application was supported by two phase 3 trials conducted in China and one conducted in the United States. Surufatinib is a novel, oral angio-immuno kinase inhibitor that inhibits the tyrosine kinase activity associated with vascular endothelial growth factor receptors (VEGFR) and fibroblast growth factor receptor (FGFR)

The third is toripalimab, an anti-PD-1 monoclonal antibody to treat patients with metastatic nasopharyngeal carcinoma. Developed by Coherus BioSciences and Shanghai Biosciences, toripalimab is being studies in combination with gemcitabine and cisplatin for first-line treatment of this cancer. The BLA is supported by the results from clinical studies POLARIS-02 and JUPITER-02. The POLARIS-02 study is pivotal phase 2 clinical study, and the results were published online in January 2021 in the Journal of Clinical Oncology.

Toripalimab is also being studied in other cancer, including esophageal squamosa cell carcinoma, lung and breast cancer, melanoma, lymphoma, and neuroendocrine neoplasms.