Oncopeptides Prepares NDA for Accelerated Approval of Ygalo as Treatment for Refractory Multiple Myeloma

Oncopeptides is preparing to submit a new drug application (NDA) with the U.S. Food and Drug Administration (FDA) to seek accelerated approval of Ygalo (melflufen) to treat patients with triple-refractory multiple myeloma.

Ygalo is a lipophilic peptide-conjugated alkylator that works by rapidly delivering a cancer-killing agent (an alkylating peptide) to malignant myeloma cells. It does so once it comes into contact with enzymes that break down amino acids from proteins and peptides, called aminopeptidases.

Although these enzymes can be found in all types of cells, they are overly produced by malignant cells from different types of cancer, including multiple myeloma. For this reason, the medication preferentially targets and destroys cancer cells containing excessive amounts of these enzymes, while leaving healthy cells unharmed.

The medication is intended to work as a therapy for triple refractory patients with multiple myeloma — patients who received and failed to respond to treatment with at least one immunomodulatory drug (IMiD), one proteasome inhibitor, and one anti-CD38 monoclonal antibody.

The announcement came after the company spent this spring discussing with the FDA whether its investigational therapy might be eligible for accelerated approval based on promising interim data from the ongoing HORIZON Phase 2 trial (NCT02963493).

HORIZON is a single-arm, open-label, Phase 2 trial that has been designed to assess the therapeutic potential of Ygalo in combination with dexamethasone in a group of patients with multiple myeloma who had been treated previously with at least one IMiD and proteasome inhibitor, and failed to respond to Pomalyst (pomalidomide) and/or Darzalex (daratumumab).

According to interim data recently announced by the company, approximately one third of the patients eligible to measure treatment response had more than 50% reduction in tumor burden. The treatment also seemed to be beneficial for high-risk patients, who had treatment responses of about 20%.

At the time of data cut-off, the median progression-free survival (the time patients lived without their disease worsening) was four months. Therapy discontinuations due to adverse events (side effects) occurred in a relatively low percentage of patients (13%). No deaths directly associated with treatment were reported.

As a result of the discussions with the FDA, Oncopeptides is preparing the submission of an NDA for Ygalo based on the latest clinical data generated by HORIZON. According to the company, the NDA submission should happen during the first quarter of 2020. If successful, it may lead to the market approval of Ygalo in the U.S. next year.

“We are very excited over the opportunity to help patients with triple-class refractory multiple myeloma who currently have very limited treatment options to potentially access a new treatment alternative that may have a large impact on their lives. The outcome of the regulatory discussions during the spring is even better than we anticipated and is a major milestone for Oncopeptides as it means that we can start the application process and potentially attain market approval significantly earlier than planned,” Jakob Lindberg, CEO of Oncopeptides, said in a press release.

“Potential approval will of course depend on the formal FDA review once we have submitted the application, but based on the discussions and the data at hand, we believe we have a very good chance to secure an approval, provided that the results generated in the HORIZON trial continue to be in line with the data we have seen so far. It will therefore be very exciting to present updated HORIZON data at the European Hematology Association (EHA) meeting in Amsterdam on June 16,” Lindberg said.