Sanofi Myeloma Drug Shines But Darzalex Dominates Still
Executive Summary
While data on Sanofi's anti-CD38 antibody isatuximab impressed at ASCO, analysts believe that the position of Johnson & Johnson's Darzalex in the multiple myeloma space is unlikely to be threatened.
Data on Sanofi's multiple myeloma (MM) candidate isatuximab have gone down well at the American Society of Clinical Oncology meeting in Chicago but it remains to be seen whether it can compete with Johnson & Johnson's blockbuster and fellow anti-CD38 antibody Darzalex.
Having presented positive topline results from the Phase III ICARIA-MM trial in February, the French firm has unveiled the full data set at ASCO. Isatuximab combined with the standard of care - Celgene Corp.’s Pomalyst (pomalidomide) and the corticosteroid dexamethasone - showed statistically significant improvements compared with pom-dex alone in patients with relapsed/refractory MM. Specifically, treatment with the triple combo led to a 40% improvement in progression-free survival (11.53 months versus 6.47 months) compared with pom-dex, an outcome described as noteworthy by Paul Richardson of the Dana-Farber Cancer Institute and principal investigator, "because this trial included a particularly difficult-to-treat, relapsed and refractory patient population that was, in my view, highly reflective of real-world practice.”
Sanofi also highlighted that the isatuximab combination therapy demonstrated a significantly greater overall response rate compared with pom-dex alone (60% versus 35%) consistently across multiple subgroups, including patients 75 years and older, patients with renal insufficiency, and patients who were refractory to Celgene's MM blockbuster Revlimid (lenalidomide).
The isatuximab/pom-dex combo was filed with the European Medicines Agency and the US Food and Drug Administration earlier this year and approval is widely expected. However, it will be up against J&J's big-selling Darzalex (daratumumab) and more positive data presented on the Genmab AS-partnered drug at ASCO emphasized the size of the challenge awaiting Sanofi.
Results from the Phase III CASSIOPEIA study showed that the addition of Darzalex to J&J/Takeda Pharmaceutical Co. Ltd.'s Velcade (bortezomib), thalidomide and dexamethasone (VTD) before and after autologous stem cell transplantation resulted in deeper responses and longer PFS compared with VTD alone in patients with newly diagnosed multiple myeloma who are transplant eligible.
Results from the first part of CASSIOPEIA, presented for the first time as part of an oral session at ASCO, showed a stringent complete response rate in the Darzalex/VTD arm of 28.9% compared with 20.3% for VTD, which is the standard of care in the US for induction therapy. A couple of days before the ASCO presentation, the FDA granted a priority review to Darzalex/VTD for frontline MM, setting an action date of 26 September. (Also see "Darzalex Excites As Potential Grows In Multiple Myeloma" - Scrip, 30 Oct, 2018.)
More good news for J&J came with the confirmation in the Phase III COLUMBA trial of the non-inferiority of subcutaneous (SC) versus intravenous (IV) Darzalex. Overall response rates were 41% SC vs. 37% IV, with median PFS and overall survival comparable, plus a significantly lower rate of infusion-related reactions (13% SC vs 35% IV). On top of that, the results confirmed the drastically shorter time of injection (five minutes) compared with seven hours for the first IV infusion.
Responding to the ASCO news, analysts at Deutsche Bank wrote in an investor note that the Phase III data for isatuximab were "compelling on a stand-alone basis [and] well received as it provides physicians and patients with a further treatment option." However, they believe isatuximab "is likely to play only a niche role and seems unlikely to threaten the dominance" of Darzalex, sales of which they expect to reach $7.2bn in 2023.
The broker argued that the 40% reduction in PFS falls short of the 60% or so benefit demonstrated with the addition of Darzalex to standard treatment regimens in the relapsed/refractory setting, "albeit in less refractory patients." Although isatuximab benefits from a shorter infusion time (three hours vs four-seven with Darzalex), "this now looks likely to be redundant given compelling data for SC-delivered Darzalex."
Deutsche Bank pointed out that speakers at ASCO suggested a possible role in patients with asthma and/or chronic obstructive pulmonary disease "given isatuximab’s lower complement activation" but the analysts agreed with consensus forecasts that the drug's sales in 2023 will be in region of €360m.
Analysts at Jefferies noted that both the Darzalex and isatuximab data were positively received at ASCO, "further cementing the role of anti-CD38s in MM." They added that "whilst feedback suggests we cannot yet say if one is superior to the other, or how/if they could be cycled, we feel that Darzalex's entrenched position is unlikely to be threatened on data to date," particularly given that the SC formulation of the latter could be approved next year.
Even without the SC approval, Jefferies concluded that by 2020, "Darzalex is likely to be entrenched as a backbone of first/second line treatment, where duration on drug is years not months, hence the competitive impact [from isatuximab] is probably minimal."