Sanofi said Tuesday that Sarclisa (isatuximab) reduced the risk of disease progression or death by 47% compared to standard of care in a Phase III study in patients with relapsed multiple myeloma. The company reported last month that the IKEMA trial had met its primary endpoint at its first planned interim analysis, with the results released early based on the recommendation of an independent data monitoring committee.
"This is the second Phase III trial to demonstrate superior results with Sarclisa combination therapy over a standard of care regimen, adding to the growing body of evidence that our anti-CD38 monoclonal antibody has the potential to make a meaningful difference for patients," commented John Reed, global head of R&D at Sanofi. "We believe Sarclisa has the potential to become the anti-CD38 of choice for the treatment of multiple myeloma," he added.
The IKEMA trial involved 302 patients who had received one to three prior anti-myeloma therapies. Participants were randomly assigned Sarclisa plus standard of care, consisting of Amgen's Kyprolis (carfilzomib) and dexamethasone, or standard of care alone. The primary endpoint is progression-free survival (PFS), while secondary goals include overall response rate (ORR), the rate of very good partial response (VGPR) or greater, minimal residual disease (MRD), complete response (CR) rate and overall survival (OS).
According to Sanofi, median PFS was 19.15 months for patients given standard of care, but had not yet been reached for patients in the Sarclisa combination arm at the time of the pre-planned interim analysis.
'Considerable depth of response'
In regards to secondary objectives, Sanofi reported no statistically significant difference in ORR, with rates of 86.6% for the Sarclisa combination and 82.9% for standard care alone. The CR rate was 39.7% among Sarclisa-treated patients versus 27.6% in the comparator group, while rates of VGPR were 72.6% and 56.1%, respectively. Sanofi also said the Sarclisa regimen "delivered considerable depth of response, with undetectable levels of MM in nearly 30% of patients" at 10-5 sensitivity as measured by next-generation sequencing. Meanwhile, OS data were still immature at the time of the interim analysis.
Sanofi said Sarclisa's safety and tolerability profile in the trial was consistent with what has been observed previously, with no new safety signals observed. The company stated that treatment-emergent serious adverse events and fatal treatment-emergent adverse events were similar in the Sarclisa combination and standard care-only arms of the trial, reporting 59.3% versus 57.4%, and 3.4% versus 3.3%, respectively. Respiratory infections classified as grade 3 or higher were seen in 32.2% of patients in the Sarclisa group versus 23.8% of those in the comparator arm, while cardiac failure that was grade three or higher was reported in 4% and 4.1% of patients, respectively.
The company indicated that interim results will be presented at the European Hematology Association (EHA) virtual congress in mid-June and will form the basis of global regulatory submissions later this year.
Sarclisa gained FDA approval in March, based on positive results from the Phase III ICARIA-MM trial, for use in combination with Bristol Myers Squibb's Pomalyst (pomalidomide) and dexamethasone in adults with relapsed refractory MM who have received at least two prior therapies. On Tuesday, Sarclisa was also cleared for the same indication by regulators in Europe.
For related analysis on the IKEMA results, see ViewPoints: Sanofi plays up Sarclisa's chances in MM.
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