Sanofi trumpets Darzalex rival isatuximab in refractory myeloma

Sanofi’s plans for a comeback in cancer have taken a step forward with new data on its anti-CD38 candidate isatuximab in multiple myeloma, already filed in the US and Europe. Headline results from the first phase 3 ICARIA-MM trial of isatuximab were reported earlier this year, but the actual data was revealed for the first time at the ASCO congress in Chicago – and according to analyst Vamil Divan at Credit Suisse looks “strong” and “pivotal”, likely setting up approvals. Isatuximab almost doubled the response rate when added to a standard myeloma regimen of Celgene’s Pomalyst/Imnovid (pomalidomide) and low-dose dexamethasone from 35% to 60%, whilst extending progression-free survival (PFS) to 11.5 months compared to 6.5 months, a 40% risk reduction. There was also a trend towards an improvement in overall survival, although that data isn’t yet mature. Lead investigator Paul Richardson of the Jerome Lipper Multiple Myeloma Centre at the Dana-Farber Cancer Institute said the results were particularly remarkable given that patients enrolled into the trial were “a particularly difficult-to-treat, relapsed and refractory patient population.” If approved, isatuximab will be the first direct rival to Johnson & Johnson and Genmab’s multiple myeloma blockbuster Darzalex (daratumumab), which has ramped away in the market since its approval in 2015 despite a number of other approvals for rival therapies around the same time. A string of clinical trial results that have moved Darzalex inexorably up the treatment pathway to include newly-treated myeloma patients helped the drug top $2 billion in sales last year and grow another 45% year-on-year to $629m in the first quarter of this year. That leaves Sanofi with a bit of a mountain to climb with isatuximab as a latecomer to market. It has pointed to a simpler infusion regimen with its drug compared to J&J’s antibody, which can take up to eight hours to deliver, but J&J and Genmab have an answer to that as well. At ASCO the partners reported phase 3 data with a subcutaneous formulation that can be delivered in a few minutes and seems to offer equivalent efficacy to the IV formulation. Meanwhile, additional anti-CD38 drugs could be on the way from MorphoSys and Takeda, which have candidates at the pivotal trial stage. Divan said that new formulation make it more likely that “the position Darzalex has built in the market will allow it to continue to dominate.” Sanofi however thinks it’s still all to play for however, particularly as it still has trials to readout in earlier-stage myeloma patients – including newly-diagnosed patients – as well as additional combinations that it hopes could carve out a position for the antibody. Isatuximab is one of two main programmes that Sanofi is hoping will spearhead a renaissance for its cancer business, which has fallen behind competitors in recent years after being a strong force in the 1990s. Its other main project Libtayo (cemiplimab), a PD-1 inhibitor that is the first drug in the cancer immunotherapy category to be cleared for cutaneous squamous cell carcinoma (CSCC), a form of skin cancer. As well as CSCC, Sanofi has phase 3 trials ongoing for cemiplimab in cervical cancer – another area where there is limited competition immunotherapies – as well as non-small cell lung cancer. It’s also looking at the combination of isatuximab and cemiplimab in myeloma and lymphoma as well as solid tumours.