On February 26th, 2019, the Oncologic Drugs Advisory Committee assembled to determine the fate of Karyopharm Therapeutics’ latest drug.
On February 26th, 2019, the Oncologic Drugs Advisory Committee assembled to determine the fate of Karyopharm Therapeutics’ latest drug, Selinexor (NDA 212306). Selinexor, an oral XPO1 inhibitor, is formulated to be used in combination with dexamethasone, for the treatment of patients with relapsed refractory multiple myeloma who have received at least three prior therapies and whose disease is refractory to at least one proteasome inhibitor, at least one immunomodulatory agent, and an anti-CD38 monoclonal antibody.
Multiple myeloma is cancer of plasma cells. Treatment kills the majority of the myeloma cells, but when a few survive it is referred to as minimal residual disease. These cells may grow and divide leading to relapse, which is very common. Multiple myeloma is described as refractory when the cancer does not respond to treatment or comes back within 60 days after the patient’s last therapy. The American Cancer Society estimates that in 2019 there will be 32,100 new cases of multiple myeloma diagnosed in the United States, and 12,960 deaths will occur.
In this meeting, there was one discussion question and one voting question. The vote was to determine whether to delay approval of Selinexor until the results of Karyopharm Therapeutics’ Phase 3 trial BOSTON are available. BOSTON is designed to confirm the clinical benefit of Selinexor in combination with bortezomib and low-dose dexamethasone against bortezomib and low-dose dexamethasone alone. However, waiting for results would delay the approval for at least 2 years. The vote resulted in 8 YES, 5 NO, and 0 ABSTENTION.
The vote relied primarily on the results from the clinical trial KCP-330-012 (STORM).
Panelists that voted for a delay felt that data from the STORM trial did not meet the FDA regulatory standards needed to confirm the safety and effectiveness of Selinexor. “I believe there is a probable benefit of Selinexor and dexamethasone for some triple-class refractory myeloma patients, and of course I completely understand the urgent need to develop novel agents with novel mechanisms of action for these patients who have exhausted standard options, but as we heard, there are real toxicities with this combination, and this may not be the right dose,” stated Dr. Alice Shaw. Nonetheless, some panelists thought there was a great need from patients for this indication, stating “I think what we have is a transient situation between now and when more data come in the BOSTON trial and other data, and I think we do patients some potential benefit here if this agent is used constructively and intelligently while we wait for the additional data in a population that is not naive to side effects.”
The agency is not obligated to follow its panel’s recommendation, but normally does so. However, on July 3, 2019, the FDA granted the accelerated approval for Selinexor. Taking the panelists’ concerns into account they modified the indication to adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody. As a condition of accelerated approval, further clinical trials may be required to verify and describe Selinexor’s benefit.
ISS has two decades of experience in developing regulatory strategies including support for FDA Advisory Committee meetings. We are involved in more FDA AdComms per year than even the largest pharmaceutical companies. For more information on how ISS can help you prepare for your next meeting, contact firstname.lastname@example.org.
Over the past few years, the number of ex-US manufacturers submitting a Class II exempt 510k device registration has increased substantially. For companies with medical devices that are approved and successful in a foreign market, the logical next step is to introduce their product into the US, which has one of the most lucrative healthcare markets in the world. Read more
FDA advisory committee meetings are important regulatory events for many manufacturers on the path to marketing approval. These meetings can quite literally result in the approval or rejection of a product based on the panel’s vote. Read more
One of the main challenges our clients face is determining which regulatory pathway is best for their products. For example, what if an OTC product has a Monograph active ingredient but that ingredient is present at a different amount than the permitted amount? Or what if the label claims a novel indication not specified in a Monograph? If you are debating pursuit of either regulatory pathway for your OTC drug, it is critical to consider cost, timeline, and label claims to ensure your products has a unique stance in today’s market. Read more
US distributors and agents trying to import rapid antibody tests for coronavirus face a number of obstacles. The good news is that FDA has opened up the Emergency Use Authorization (EUA) program to include SARS-CoV-2 (the virus) and COVID-19 (the disease), expediting time to market. Read more
The journey to scientific and commercial success is often complex and always critical, if you are looking for an expert partner to help steer you to confident solutions, contact us todayContact us