Ide-cel Granted FDA Priority Review for Heavily-treated Multiple Myeloma

The U.S. Food and Drug Administration (FDA) has granted priority review to Bristol Myers Squibb and Bluebird Bio‘s application requesting the approval of idecabtagene vicleucel (ide-cel) for the treatment of adults with multiple myeloma.

The biologics license application (BLA), resubmitted in August, is seeking ide-cel’s approval for myeloma patients who failed to respond to at least three prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody.

The U.S. agency has set a Prescription Drug User Fee Act action date of March 27, 2021, meaning that a decision on whether to approve this investigational CAR T-cell therapy is due by then.

Meanwhile, a similar application is being reviewed by the European Medicines Agency (EMA), which granted it accelerated assessment in March, reducing the maximum timeframe for review to 150 days. Bristol Myers is also planning to submit additional applications requesting the approval of ide-cel in other countries.

“Today’s priority review milestone recognizes the potential of this first anti-BCMA CAR T-cell therapy to address a critical unmet need of patients with multiple myeloma,” Stanley Frankel, MD, senior vice president of cellular therapy development at Bristol Myers Squibb, said in a press release.

“We are pleased by the significant progress that is being made in partnership with patients and the multiple myeloma community to bring ide-cel to adults with relapsed and refractory multiple myeloma who are triple-class exposed and may benefit from an important new therapeutic option,” he said.

Ide-cel, formerly known as bb2121, is a type of immunotherapy in which a person’s own T-cells — a type of immune cell — are collected and genetically modified in the lab to better fight cancer, after which they are expanded and infused back into the patient.

Specifically, ide-cel contains T-cells engineered to produce a man-made chimeric antigen receptor, or CAR, that helps them recognize and kill cells containing the B-cell mature antigen (BCMA) — a protein found at high levels on the surface of multiple myeloma cells — while leaving healthy cells unharmed.

The experimental therapy has been given the designations of breakthrough therapy by the FDA, and priority medicine by the EMA for the treatment of relapsed or refractory multiple myeloma.

Both approval requests were based on data from the KarMMa Phase 2 trial (NCT03361748), which is assessing the safety and efficacy of ide-cel in patients who received at least three prior lines of therapy and failed to respond to their last treatment regimen.

The study’s main goal was to assess the percentage of patients responding to a single infusion of ide-cel within a period of two years. Secondary goals included the percentage of patients attaining complete responses (complete cancer eradication), the time to response, the duration of responses, and the time they lived without disease worsening.

From the 140 patients enrolled in the trial, 128 received ide-cel at a target dose level of 150 million to 450 million modified T-cells.

Data from KarMMa, presented at the 2020 American Society of Clinical Oncology Virtual Scientific Program, showed that at a median follow-up of 11.3 months, 73.4% of patients responded to treatment within a period of two years, with 31.3% achieving complete responses. The median duration of response was 10.6 months, and the median time patients lived without disease progression was 8.6 months.

The most common adverse events reported during the study were cytopenias (low blood cell counts; 97%) and cytokine release syndrome (CRS; 84%), which were consistent with those reported in previous studies.

Most cases of CRS — a serious immune reaction that can be triggered by certain forms of immunotherapy, including CAR T-cell therapy — were mild (grade 1) or moderate (grade 2) in severity.

“Today’s acceptance of the BLA for ide-cel for priority review by the FDA marks a key moment in our journey to bring this BCMA-directed CAR T cell therapy to multiple myeloma patients who are in desperate need of new options,” said Joanne Smith-Farrell, PhD, chief operating officer of oncology at Bluebird Bio.

“Based on the body of evidence we have generated in an advanced, heavily pre-treated patient population, our confidence in the potential of ide-cel as an important treatment option remains high,” she added. “Together with our partners at Bristol Myers Squibb, we are committed to continue working with the FDA to deliver this promising therapy to patients in an expeditious manner.”