- Pfizer has paused enrollment in a pivotal trial of a closely watched cancer drug candidate, an experimental dual-targeting antibody treatment for multiple myeloma.
- In an earnings release Tuesday, Pfizer said that three cases of peripheral neuropathy were reported in a Phase 1 study of the drug, known as elranatamab. As a result, the company has halted a Phase 2 trial meant to support approval of the drug while the company provides "additional information" to the Food and Drug Administration.
- The disclosure is a setback for Pfizer in one of the more competitive areas of cancer drug development. Elranatamab is one of several so-called bispecific antibody drugs in clinical testing in multiple myeloma. The hope is these treatments may be as potent, but more convenient, than cell-based treatments that have recently emerged for the deadly bone marrow cancer. Pfizer's drug is among the furthest along.
Treatment for multiple myeloma is changing fast. Adding to the array of drugs approved in the past decade, the FDA recently cleared the first cell therapy for the condition, known as Abecma from Bristol Myers Squibb and Bluebird bio. Cilta-cel, a similar product from Johnson & Johnson and Legend Biotech, could soon follow.
Those two treatments are part of a new wave of medicines that work differently than the multiple myeloma drugs of the past. Targeting a protein called BCMA that's found on cancerous B cells but not healthy ones, these medicines offer a new way to drive multiple myeloma — a persistent cancer from which patients often relapse — into remission.
The BCMA drugs on the market or close to it have notable flaws, however. Cell therapy, though very powerful and durable when it works, is complex and can sometimes trigger severe neurological and immune-related side effects. GlaxoSmithKline's Blenrep — an antibody linked to a cancer-killing toxin — is more convenient, but less effective and is associated with severe eye-related side effects.
An advancing group of bispecific antibodies including elranatamab could offer some advantages. These drugs latch onto BCMA and a target on immune cells called CD3. Drugmakers hope they'll be nearly as effective as cell therapy, but safer and easier to distribute — particularly among the community doctors that treat a majority of multiple myeloma patients.
Regeneron, Amgen, J&J and AbbVie, along with Pfizer, each have similar BCMA-targeting bispecific antibodies in clinical testing. Each has shown promise, though crucial questions remain, like how potent and durable they are and what their side effect profile looks like.
Pfizer has highlighted elranatamab as one of its star oncology drug candidates and in February sped the drug into a Phase 2 study, MagnetisMM-3, meant to support an approval filing. Unlike some of the other antibodies in development, elranatamab is administered through a subcutaneous injection rather than an intravenous infusion.
Results from a 30-patient Phase 1 trial showed treatment with the drug led to responses in 83% of participants, a third of whom went into remission. Cases of cytokine release syndrome, a potentially lethal side effect common to cell therapy, were judged mild to moderate.
"We believe [elranatamab] is highly competitive against anything else in this space and one of the most active drugs for this disease," said Chris Boshoff, Pfizer's oncology chief development officer, in an interview earlier this year. Boshoff also noted the drug's potential to be distributed globally, whereas CAR-T is only available at specific treatment centers in a limited number of countries.
MagnetisMM-3 is testing elranatamab in roughly 150 patients whose disease progressed despite treatment with one of the three major classes of multiple myeloma drugs and includes a group of patients previously exposed to a BCMA-based treatment. But Pfizer has been planning other pivotal studies for later this year, such as combination trials with standard of care or new drugs in earlier treatment lines, Boshoff said.
According to Eamonn Nolan, a Pfizer spokesperson, more than 100 patients have been given elranatamab and the three cases of peripheral neuropathy were reported "over time." The FDA paused enrollment on April 20 while Pfizer collects more information, but enabled treatment to continue for patients who are benefiting.
In an email to BioPharma Dive, Nolan added that "various types of peripheral neuropathy have been reported in published literature" for other approved and investigational multiple myeloma drugs, among them treatments that target BCMA.
"We have collected information about the cases, and the formal response package will be submitted to the FDA," Nolan said.
The MagnetisMM-3 study has a primary completion date of June 2022, according to clinicaltrials.gov.