J&J's BCMA bispecific Tecvayli wins FDA approval in multiple myeloma—but as a late-line therapy

After European regulators jumped on a global-first approval for Johnson & Johnson’s BCMA-targeted bispecific drug Tecvayli, the U.S. FDA has doled out its own blessing for the novel therapy. But the U.S. nod covers what appears to be a less favorable treatment setting.

The FDA has granted an accelerated approval for Tecvayli, or teclistamab, to treat relapsed or refractory multiple myeloma, the agency said Tuesday. To be eligible for Tecvayli, patients must have tried at least four prior lines of therapy, including a proteasome inhibitor such as Takeda’s Velcade, an immunomodulatory agent like Bristol Myers Squibb’s Revlimid and a CD38 antibody such as J&J’s Darzalex. A line of therapy can include various combinations of drugs.

The U.S. indication appears to be more limited than Tecvayli’s European label, which allows the drug as long as patients have received three prior therapies. It also puts Tecvayli in the same spot as J&J and Legend Biotech’s BMCA-targeted CAR-T therapy Carvykti in the fifth-line treatment setting in the U.S.

Still, as the FDA noted, Tecvayli represents the first bispecific BCMA-directed CD3 T-cell engager approved in the U.S. The drug targets both BCMA expressed on the surface of myeloma cells and CD3 on the surface of T cells, thereby inducing T-cell activation and subsequent killing of the cancer cells.

J&J is selling Tecvayli at a list price of $39,500 per month, a company spokesperson told Fierce Pharma. Clinical trial experience suggests an average patient takes the bispecific for about nine months to 10 months, the spokesperson noted. That brings the total cost of Tecvayli to around $355,500 to $395,000 on average, before any rebates or discounts.

For Carvykti, the one-time treatment bears a list price of $465,000.

Tecvayli scored FDA approval based on tumor shrinkage data from the MajesTEC-1 study, which evaluated the J&J drug in heavily pretreated myeloma patients who had received three or more lines of therapies. In a group of 110 patients who had no prior BCMA-targeted therapy, Tecvayli shrank tumors in 61.8%, including 28.2% who enjoyed a complete response or better. 

As the FDA noted, 78% of the 110 patients had tried at least four prior lines of therapy, and the median number of prior lines was five.

Previously, the FDA approved Carvykti in the fifth-line myeloma setting even though its clinical trial had enrolled a broader patient population, including those who’d tried just three prior lines of treatment. The FDA made that call because of a relatively low representation of fourth-line patients in Carvykti's study.

Like Carvykti, Tecvayli comes with some dangerous potential side effects, including cytokine release syndrome and neurologic toxicity. So the FDA has slapped a boxed warning on Tecvayli’s label and required that the drug be available only through a monitoring program known as Risk Evaluation and Mitigation Strategies (REMS).

But unlike Carvykti, which takes a long time and several complicated steps to manufacture, Tecvayli is an off-the-shelf product that’s given through under-the-skin injections.

The REMS requirement was unexpected, SVB Securities analysts said in a Wednesday note. While the extra hurdle likely won’t affect treatment decisions at large academic centers, it could result in “slightly more cautious adoption” of Tecvayli in the community setting, the analysts said.

“That said, we still anticipate high demand for Tecvayli given its compelling efficacy, likely unconstrained supply, and ease of adoption relative to CAR-T therapies,” the SVB team said.

SVB believes Tecvayli may eventually reach more than $2 billion in peak sales, noting that BMS’ blockbuster multiple myeloma drugs Pomalyst and Revlimid also have REMS programs.

The FDA reviewed Tecvayli under Project Orbis, a program that enables concurrent submission and evaluation of oncology drugs among international regulators. Authorities in Australia, Brazil, Canada and Switzerland also participated in Tecvayli’s application and will make their own decisions on the drug.

Tecvayli joins a growing army of BCMA agents for multiple myeloma. Besides J&J and Legend's Carvykti, Bristol Myers Squibb also sells BCMA-targeted CAR-T therapy Abecma, and GSK has an antibody-drug conjugate called Blenrep.

Currently, all four BCMA drugs are relegated to fifth-line treatment, but they aim to leap forward in the treatment order. J&J is combining Tecvayli with Darzalex in the phase 3 MajesTEC-3 trial in patients who have received one to three prior lines of therapy. Part of SVB’s $2 billion peak sales estimate comes from the potential of this combination.

Because the current late-line use is cleared under the accelerated approval pathway, J&J is on the hook to provide confirmatory evidence. The company has agreed to a confirmatory trial with the FDA, the J&J spokesperson said, but he declined to answer whether MajesTEC-3 is that study.

Editor's Note: The story has been updated with pricing and confirmatory trial comment from J&J and analysis from an SVB Securities note.