FDA verdict on Sanofi’s Darzalex rival is due in April 2020

Johnson & Johnson’s multiple myeloma drug Darzalex has had the anti-CD38 category to itself since 2015, but could face competition from Sanofi’s isatuximab next year.

The FDA has formally kicked off its review of isatuximab as a treatment for relapsed/refractory multiple myeloma, with a standard 10-month review and an action date of 30 April 2020.

If approved, isatuximab will be the first direct rival to $2.0bn blockbuster Darzalex in the US, which accounted for well over half the product’s sales last year. It is also under regulatory review in Europe.

Sanofi filed for approval of isatuximab on the strength of the ICARIA-MM trial reveal that the CD38-targeting antibody was able to prolong progression-free survival (PFS) when added to a standard myeloma regimen of Celgene’s Pomalyst/Imnovid (pomalidomide) and low-dose dexamethasone.

The French drugmaker says the trial was the first to show that an antibody has been shown to improve PFS when added to what is a standard second-line treatment regimen for relapsed myeloma patients.

There was also a trend towards improved overall survival, although that data isn’t mature yet, and the FDA’s review time suggests it does not view the drug as an advance over Darzalex.

Isatuximab will certainly need all the help it can get if it is to chase down J&J’s drug, which has steadily moved up the treatment pathway in myeloma and is now approved for use in previously-untreated patients in combination with other drugs.

Analyst Vamil Divan at Credit Suisse said last month when the ICARIA-MM data was presented in full at ASCO that the data looked strong enough to support approval, but pointed out that J&J and its partner Genmab are already working on a new rival that could blunt isatuximab’s impact.

Sanofi has pointed to a shorter two-hour infusion for isatuximab that could be an advantage over Darzalex, which has to be given over eight hours. However, J&J and Genmab have phase 3 results with a subcutaneous formulation of daratumumab that can be delivered in just a few minutes.

The French drugmaker also thinks that isatuximab could be safer to use in patients with inflammatory diseases like asthma, as unlike Darzalex, it is not associated with complement activation, and will also be suitable for use in Darzalex treatment failures as it targets a different part of CD38.

Additional competition is however looming from MorphoSys and Takeda, which each have anti-CD38 drugs in pivotal-stage testing for myeloma, while another rival is Bristol-Myers Squibb and AbbVie’s already-marketed Empliciti (elotuzumab), which targets SLAMF7 and is vying for market share.

Empliciti picked up an additional approval from the FDA as a third-line therapy for myeloma in combination with pomalidomide and dexamethasone last November.