Go or go go? J&J’s cell therapy heads to the FDA

Johnson & Johnson's ciltacabtagene autoleucel could soon become the second approved cell therapy for multiple myeloma, with its Pdufa date falling towards the end of next month. The BCMA-targeted Car-T therapy is gunning to take on Bristol Myers Squibb/Bluebird's Abecma, and boasts better efficacy. 

Elsewhere, Biomarin is taking its achondroplasia project back to the regulators after submitting durability data, while a panel will decide whether molnupiravir, Merck & Co/Ridgeback’s oral Covid-19 antiviral, has safety in hand. 

Second place, but for how long? 

Cilta-cel’s filing was based on Cartitude-1, an open-label study in relapsed/refractory multiple myeloma patients who had received at least three prior lines of therapy or were double-refractory to a proteasome inhibitor and immunomodulatory drug. 

Efficacy reported at this year’s Asco was impressive, with the overall response rate in 97 patients hitting 98%, including an 80% complete response rate and median progression-free survival of nearly 23 months.

Bristol Myers Squibb/Bluebird's Abecma, which was approved for fifth-line use back in March, cites 72% ORR and a 28% complete response rate on its label.  

Abecma’s label also includes a black box warning of haemophagocytic lymphohistiocytosis/macrophage activation syndrome and cytopenia, in addition to the cytokine release and neurotoxicities that are standard with Car-T therapies. Cilta-cel will probably contain a similar warning, and has been associated with higher neurotoxicity than Abecma.

Greater opportunity lies in earlier lines of therapy, but toxicity could hold up both Abecma and cilta-cel. 

Durability still a question 

In August Biomarin’s vosoritide, now called Voxzogo, became the first medicine approved in Europe for the treatment of children aged two and over with achondroplasia. A decision in the US is due in November after a three-month delay.  

Biomarin’s original NDA filing included one-year phase 3 data in children over five years old given daily injections of Voxzogo. The FDA, however, expressed a desire for two-year controlled data to ensure that the efficacy of Voxzogo was durable. In Europe one-year data had been enough for approval. 

Additional data from the open-label extension study were subsequently submitted to the US regulator, though this did not include a direct placebo-controlled comparison. Durability was shown through a comparative analyses of participants randomised to the active arm versus participants on placebo with two years' untreated follow-up.  

Voxzogo is forecast to become the top-selling achondroplasia project in 2026, according to Evaluate Pharma consensus. Ascendis’s Transcon CNP, the most advanced rival, is still only in phase 2. But Ascendis is going for convenience, testing once-weekly treatment, with an update from two placebo-controlled trials due this quarter. 

Molnupiravir’s panel 

Safety will likely dominate the discussion at a November 30 US adcom for Merck & Co and Ridgeback’s molnupiravir. The oral antiviral yielded impressive results last month in Covid-19 outpatients, but some concern has been voiced over its potential for mutagenicity.  

Molnupiravir works by causing a large number of genetic mutations in the replicating virus, and the worry is that mutations might also occur in the RNA of patients who take it, though Merck insists that it has not found anything worrying.  

If given backing, and a subsequent approval, molnupiravir offers convenience advantages versus infused antibodies. Another phase 3 study, Move-Ahead, in post-exposure prophylaxis is due to report next year. 

The tables below list first-time and supplementary US approvals, as well as advisory committee meetings due next month, with consensus forecasts from Evaluate Pharma.