Margarida Maia, PhD - Science Writer

Oncopeptides received a positive opinion from an arm of the European Medicines Agency (EMA) that is expected to take the company one step closer toward European Union approval to market Pepaxti (melphalan flufenamide, also called melflufen) in combination with dexamethasone for hard-to-treat multiple myeloma. With the Committee for Medicinal Products for Human Use (CHMP) opinion in hand, the company can expect the European Commission, which has the authority to approve medicines for use throughout the EU, to make a final decision within two months. If the European Commission gives its green light, the marketing approval will be valid in all EU countries as well as in Iceland, Liechtenstein, and Norway, with a planned launch toward the year’s end in Germany, Oncopeptides announced in a press release. No post-marketing studies would be required. Pepaxti, used in combination with the corticosteroid dexamethasone, is intended to treat adults with multiple myeloma who have received at least three prior lines of therapies. Their disease should be resistant (refractory) to at least one proteasome inhibitor, one immunomodulator, and one CD38 inhibitor, and to have progressed during or after the last therapy. For patients with a prior autologous stem cell transplant, the time to progression should be at least three years from transplantation. Trials support CHMP positive opinion. CHMP's opinion is based on findings from HORIZON, a Phase 2 clinical trial (NCT02963493) wherein Pepaxti in combination with dexamethasone, was found to be safe and to bring about deep and durable responses in patients with relapsed or refractory multiple myeloma. The proportion of HORIZON patients who had a partial or complete response (overall response rate) to the treatment was 28.8%. The median time to response was 2.3 months, and the median duration of response was 7.6 months. These findings were confirmed in OCEAN, a Phase 3 clinical trial (NCT03151811) that tested Pepaxti plus dexamethasone versus Pomalyst (pomalidomide) plus dexamethasone in patients given at least two, but no more than four, prior lines of therapy. “The recommendation for full approval of Pepaxti by EMA is really good news for patients with triple class refractory disease, where the unmet medical need remains high and treatment options often are exhausted,” said Pieter Sonneveld, MD, PhD, who led the OCEAN study. Sonneveld is a professor of hematology at the Erasmus University Medical Center in Rotterdam, the Netherlands. In an update shared via webcast on June 27, the company reported better overall survival in patients with a time to progression less than three years from transplant who were treated with Pepaxti plus dexamethasone than in those on Pomalyst plus dexamethasone (median survival time of 23.6 vs. 19.8 months). This difference, however, was not significant. “EMA's assessment of Pepaxti corroborates our scientific conclusion that the overall survival result in the OCEAN study constitutes a case of true survival heterogeneity,” said Klaas Bakker, MD, PhD, executive vice president and chief medical officer of Oncopeptides. “In addition, EMA confirms that there are no toxicological safety signals in both studies and there is a positive benefit risk profile in the indicated patient population,” Bakker added. “The non-transplanted, often older patient population, which represents the largest group of RRMM [relapsed-refractory multiple myeloma] patients, particularly benefits from treatment with Pepaxti.” Toward the year’s end, Oncopeptides plans to request a change to the terms of Pepaxti's anticipated approval to allow access as an earlier line of therapy. The company is also working toward U.S. approval, and the “dialogue with the US Food and Drug Administration (FDA) has now been intensified to achieve a clear path forward also for US patients,” said Jakob Lindberg, CEO of Oncopeptides. Pepaxti belongs to a new class of compounds known as peptidase-enhanced agents. It works by rapidly delivering a cancer-killing agent — an alkylating peptide — to malignant cancer cells that contain high levels of aminopeptidases, which are enzymes that break down peptides. In this way, the therapy is designed to preferentially target and destroy cancer cells containing excessive amounts of these enzymes, while healthy cells are spared.

Margarida Maia, PhD, science writer —

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