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FDA Alert for Pepaxto (melflufen) in Multiple Myeloma
Posted: Jul 29, 2021
FDA Alert for Pepaxto (melflufen) in Multiple Myeloma image

The Myeloma Crowd by HealthTree occasionally posts results of clinical studies of interest to our family of myeloma patients and caregivers. Myeloma trials are typically ‘open label’ trials where the results only provide outcomes for either a given drug, or a given drug dosed in combination with other myeloma compounds. There are rare occasions where a drug (or combination of drugs) is/are studied head-to-head against another drug (or combination of drugs). In such cases, one may expect that one treatment ends up with better results than another. Pharmaceutical companies tend to shy away from such studies as the outcomes are uncertain (unless the comparator treatment is not true ‘standard of care’).

Since the beginning of 2021 Myeloma Crowd has posted several articles with respect to melphalan flufenamide, a novel myeloma treatment, and a drug that was FDA approved on February 26, 2021 “in combination with dexamethasone, for the treatment of adult patients with relapsed or refractory multiple myeloma, who have received at least four prior lines of therapy and whose disease is refractory to at least one proteasome inhibitor, one immunomodulatory agent, and one CD38-directed monoclonal antibody.”

At the time, Oncopeptides (the developer, manufacturer, and marketer of the drug) also announced that the company was awaiting the results of a head-to-head study of melflufen, combined with low dose dexamethasone against pomalidomide, combined with low dose dexamethasone.

The results of this study are now available and have led the US Food and Drug Administration to issue an alert that the study showed an “increased risk of death associated with Pepaxto (melphalan flufenamide)” compared to the pomalidomide-dexamethasone arm of the study. The key points of this alert are:

  • “Due to the detrimental effect on overall survival in the OCEAN trial [the head-to head comparison of melflufen-dexamethasone against pomalidomide-dexamethasone], FDA is requiring the manufacturer suspend enrollment in the trial. FDA has also suspended enrollment in other ongoing Pepaxto clinical trials.”
  • “Patients receiving clinical benefit from Pepaxto may continue treatment in the OCEAN trial provided they are informed of the risks and sign a revised written informed consent.”
  • “FDA continues to evaluate the OCEAN trial results and may hold a future public meeting to discuss these safety findings and explore the continued marketing of Pepaxto. The agency will update patients and health care professionals when new information is available.”

Oncopeptides has also released a statement, dated evenly with the FDA alert and referencing the alert. This statement reads in part:

“Patient safety is paramount to Oncopeptides. The Company has an ongoing dialogue with the FDA and will provide updated information as soon as more information becomes available. The Company plans to submit complete data from the OCEAN-study to the International Myeloma Workshop meeting in Vienna on September 8-11, 2021.”


Only time will tell what the final outcome will be in the discussion between FDA, Oncopeptides and the myeloma medical community. In the meantime, however, we urge patients currently being treated with a Pepaxto (melflufen) regimen to reach out to their physician(s) to receive personalized guidance as to what to do next.

Those readers who are interested in learning more about the study results may wish to look at the statistical addendum of the FDA alert that provides a Kaplan-Meijer curve of the study’s two arms as well as some summary statistics relating to Overall Survival.

You will see mention of something called “Hazard Ratio”. In a nutshell: 

In survival analysis, the hazard ratio (HR) is the ratio of the hazard rates corresponding to the conditions described by two levels of an explanatory variable. For example, in a drug study, the treated population may die at twice the rate per unit time of the control population. The hazard ratio would be 2, indicating higher hazard of death from the treatment.”


In this specific case, the Hazard Ratio for melflufen-dexamethasone vs. pomalidomide-dexamethasone is 1.104, meaning that the risk of death from melflufen-dex is 1.104 times higher than the risk of death from pomalidomide-dex. The OCEAN study included patients who had 2-4 prior lines of therapy, have received a proteasome inhibitor and relapsed after lenalidomide.  The statistical addendum to the FDA alert also mentions that “Additional FDA analyses of safety and efficacy are ongoing”.

The author Paul Kleutghen

about the author
Paul Kleutghen

I am a patient diagnosed in 2014 with primary plasma cell leukemia (pPCL), a rare and aggressive variant of multiple myeloma and have been very fortunate to find successful treatment at the division of Cellular Therapy at the Duke University Cancer Institute. My wife, Vicki, and I have two adult children and two grandsons who are the ‘lights of our lives’. Successful treatment has allowed Vicki and I to do what we love best : traveling the world, albeit it with some extra precautions to keep infections away. My career in the pharmaceutical industry has given me insights that I am currently putting to use as an advocate to lower drug pricing, especially prices for anti-cancer drugs. I am a firm believer that staying mentally active, physically fit, compliant to our treatment regimen and taking an active interest in our disease are keys to successful treatment outcomes.

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