After Mariposa a Carvykti leak brings J&J better news

No news is bad news for the Mariposa trial, J&J’s bid for market share in lung cancer, but Carvykti turns the frown upside down.

On Johnson’s & Johnson’s earnings call yesterday executives revealed that the closely watched Mariposa trial had passed an interim analysis without being stopped for efficacy, a disappointment that contributed to a 3% dip in the developer’s share price.

The study pits a combination of Rybrevant and lazertinib against Astrazeneca’s Tagrisso in first-line EGFR-mutant NSCLC, and is J&J’s big bid to grab share from Astra’s $5.4bn blockbuster. Because Mariposa now continues to a final analysis investors seem to be assuming that the combination’s benefit over Tagrisso will be less than hoped for; Astra’s shares jumped 2% yesterday.

With the final readout slated for the end of this year that assumption will be tested soon enough. J&J said Mariposa recruited much faster than expected, something that could mean that median follow-up was immature at interim, making it too early for any efficacy bars to be cleared, SVB Securities analysts suggested.

Still, doubts about Mariposa continue to quietly mount. The trial also tests a lazertinib monotherapy cohort, but J&J has stressed that its primary purpose is to show superiority of the combination, thus guiding away from any expectations that lazertinib might match or beat Tagrisso.


And the lack of Mariposa news was enough to rattle others hoping to follow Rybrevant, with Merus dropping 15% yesterday.

The biotech’s MCLA-129 is, like the J&J drug, a bispecific that hits EGFR and c-Met. Mariposa is the first trial to test this mechanism in a broad setting, and the data need to impress to back up some big expectations; J&J has said Rybrevant sales could reach $5bn.

Until Mariposa reads out many are likely to remain sceptical about such potential, although it is notable that Astrazeneca is not dismissing the possibility. The company will soon begin Ostara, a small phase 2 trial that curiously combines Tagrisso with Rybrevant.

It is possible that this is an insurance policy, as analysts at Wolfe Research suggest. It might also be a prelude to an in-house combo; notably, at AACR Astra presented preclinical data on AZD9592, which like Rybrevant targets EGFR and c-Met but with an antibody-drug conjugate modality. Astra recently started Egret, a phase 1 trial testing AZD9592 as monotherapy and as a combo with Tagrisso.

Bigger prospects

While investors were still digesting the Mariposa implications, better news arrived for J&J on Carvykti, although not so much for organisers of the European Haematology Meeting. Leaked abstracts revealed some keenly awaited data from the multiple myeloma Cartitude-4 trial toplined positive back in January.

A 74% reduction in the risk of relapse is much better than expected and substantially better than the 51% managed by Bristol Myers Squibb’s rival anti-BCMA Car-T therapy Abcema in the Karmma-3 trial. True, the trials were in slightly different settings, but the result almost certainly sets Carvykti up to be used in the earlier – and more valuable – second-line setting.

J&J split out Carvykti sales for the first time yesterday, with first-quarter sales reaching $74m. Manufacturing delays have held back the therapy's launch, and on a call executives said production was ramping up, with additional supply capacity recently acquired.

The Car-T therapy is expected to bring in just over $3bn by 2028 for J&J, sellside consensus from Evaluate Pharma suggest, although numbers could now rise. Consensus for Rybrevant sits just below $1bn in the same year.

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