Oncopeptides’ Accelerated Approval Filing for Ygalo in US Unimpeded by COVID-19

Despite some interruptions to Ygalo‘s clinical program due to the ongoing COVID-19 outbreak, Oncopeptides‘ application seeking its accelerated approval in the U.S. for the treatment of triple-refractory multiple myeloma will not be affected, and filing is expected mid-year, the company has announced.

“Obviously the COVID-19 pandemic has an enormous impact on us and society as a whole,” Jakob Lindberg, Oncopeptides’ CEO, said in a press release. “We are very fortunate that this does not slow down our application process for accelerated approval in U.S. and will not delay us in our effort to bring [Ygalo] to the myeloma patients.”

All patients enrolled in Ygalo (melflufen) clinical studies will continue treatment, the company stated, adding that its main goal is to avoid unnecessary exposure in this at-risk patient population, while maintaining study data integrity.

“The COVID-19 public health crisis does not decrease the medical need of myeloma patients and I firmly believe that [Ygalo] has the potential to offer a new option to those with few available treatments,” Lindberg added.

Ygalo belongs to a novel class of agents called peptidase-enhanced compounds that work through a new mechanism of action. Once inside a cell, Ygalo rapidly releases a toxic agent — an alkylating peptide — only when in contact with aminopeptidases, specific enzymes that are overly produced by malignant cells, including those in multiple myeloma.

In this way, the therapy preferentially targets and kills cancer cells containing excessive amounts of these enzymes, while leaving healthy cells unharmed.

Ygalo, which is administered into the vein (intravenously), is intended for people with triple refractory multiple myeloma who received and failed to respond to treatment with at least one immunomodulatory drug (IMiD), one proteasome inhibitor (PI), and one anti-CD38 monoclonal antibody.

Currently, Oncopeptides is evaluating Ygalo, in combination with other agents, as a potential treatment for relapsed or refractory multiple myeloma (RRMM) in four clinical trials: the Phase 1/2 ANCHOR (NCT03481556), the Phase 2 HORIZON (NCT02963493), the Phase 2 BRIDGE (NCT03639610), and the Phase 3 OCEAN (NCT03151811).

According to the company, the HORIZON and OCEAN studies are key for the submission of applications to potentially obtain Ygalo’s marketing authorization in the U.S. and Europe for the treatment of RRMM.

In particular, Oncopeptides is preparing to submit a new drug application to the U.S. Food and Drug Administration (FDA) seeking Ygalo’s accelerated approval for triple-refractory multiple myeloma based on HORIZON data.

HORIZON was designed to evaluate the therapeutic potential of Ygalo, in combination with dexamethasone, in multiple myeloma patients who had received at least two prior therapies, including an IMiD and a PI, and failed to respond to Pomalyst (pomalidomide; also sold as Imnovid in Europe by Celgene) and/or Darzalex (daratumumab).

The trial’s interim data, for 113 patients with measurable treatment response, showed that the combination therapy was safe and led to at least disease stabilization in most patients (86%) and to a more than 50% reduction in tumor burden in nearly one-third of the patients.

Final data for the 157 participants of HORIZON were collected in January, and “data analysis is now in final stages and release of topline data is expected shortly,” Oncopeptides said. It also assured that the timeline for Ygalo submission to the FDA “remains intact,” with filing expected by the end of the second quarter of the year.

OCEAN is evaluating whether the combination of Ygalo with dexamethasone is superior to current standard of care — Pomalyst plus dexamethasone — in myeloma patients who had received between two and four prior therapies and are refractory to Revlimid (lenalidomide).

According to the company, OCEAN is in its final stages of recruitment (423 out of 450 planned patients) and will continue enrollment in line with regulatory guidelines and site capabilities. Topline data are expected to be only slightly delayed, with the current number of participants already being sufficient to assess the trial’s main goal — the time a patient lives without signs of disease progression — in the future, Oncopeptides noted.

Recruitment for ANCHOR and BRIDGE studies will be put on temporary pause for patient safety reasons.

ANCHOR is evaluating the safety and effectiveness of Ygalo plus dexamethasone in combination with Velcade (bortezomib) or Darzalex in patients who had received one to four previous therapies and failed to respond to treatment with an IMiD and/or a PI.

BRIDGE is assessing Ygalo’s pharmacokinetics (uptake, distribution, and elimination in the body) in RRMM patients with impaired kidney function.

Moreover, the initiation of the LIGHTHOUSE Phase 3 trial, planned for the first quarter of the year and designed to assess whether adding Ygalo to Darzalex is superior to Darzalex alone in RRMM patients, is expected to be delayed.

“The safety and well-being of our patients continues to be our top priority and we will continue to take appropriate actions if need be to ensure their safety,” said Lindberg.

Ygalo received orphan drug designation in 2015 in the U.S. and Europe. The designation is meant to provide regulatory support and financial benefits, to accelerate the clinical development and review of Ygalo, and to ensure marketing exclusivity for a period of time upon regulatory approval (seven years in the U.S. and 10 years in Europe).