J&J bags first FDA approval for a GPRC5D drug

Johnson & Johnson has become the first drugmaker to get FDA approval for a drug targeting GPRC5D, getting the nod for its bispecific antibody Talvey for a group of patients with relapsed or refractory multiple myeloma.

The T-cell engager – which targets GPRC5D on multiple myeloma cells and CD3 on T-cells – has been cleared on the back of data from the phase 1/2 MonumenTAL-1 study, which showed an overall response rate (ORR) of more than 70% when used as a fourth-line or later treatment.

The trial included a broad range of patients, including those previously treated with BCMA-directed bispecific antibodies or CAR-T cell therapy, as well as standard earlier-line drugs like proteasome inhibitors, immunomodulators, and anti-CD38 antibody therapy.

Talvey (talquetamab) has been given accelerated approval by the FDA, which means it will only be able to stay on the market if J&J can show efficacy and safety in follow-up, confirmatory trials.

J&J's Janssen pharma subsidiary said the drug – given as a weekly or biweekly injection – will only be available under a risk evaluation and mitigation strategy (REMS). The drug has been approved with a boxed warning for cytokine release syndrome (CRS) and neurologic toxicity.

The new treatment option, one of a series of new myeloma therapies to emerge from Janssen's pipeline, was warmly welcomed by the Multiple Myeloma Research Foundation, a US patient organisation. Its chief executive, Michael Andreini, said: "Although options for the treatment of multiple myeloma have expanded significantly in recent years, the disease remains incurable."

Data from MonumenTAL-1 reported at the ASH congress last year revealed the duration of response with Talvey was at least nine months, providing invaluable extended time for patients before their disease started to progress again.

In a subgroup of patients treated with BCMA bispecifics or CAR-T therapies, the ORR was 72%, with 59% of responses lasting for at least nine months.

BCMA therapies include J&J's own bispecific Tecvayli (teclistamab) and Legend Biotech-partnered CAR-T Carvykti (ciltacabtagene autoleucel), both tipped for multibillion-dollar sales. J&J has previously said that it thinks Talvey also has considerable sales potential and is an under-appreciated asset in its pipeline.

Talvey has also been recommended for approval in the EU, setting up approval by the EMA in the coming weeks.

Other companies with GPRC5D-directed therapies in development include Roche with bispecific antibody forimtamig, Bristol-Myers Squibb with CAR-T candidate BMS-986393, and Leads Biolab with LBL-034, another CD3xGPRC5D bispecific.