ASH: Sanofi, Johnson & Johnson on collision course with Sarclisa, Darzalex 4-drug regimens in myeloma

Sanofi and Johnson & Johnson are adding more fuel to their CD38 rivalry fire between Sarclisa and Darzalex in multiple myeloma. With approvals already in place as triplet therapies, the two companies are now touting early clinical wins for four-drug regimens.

In newly diagnosed multiple myeloma patients who are eligible for transplant, adding Sanofi’s Sarclisa to a widely used regimen of Bristol Myers Squibb’s Revlimid, Takeda’s Velcade and corticosteroid dexamethasone (RVd) helped more patients achieve very low levels of minimal residual disease (MRD) in the blood system after induction therapy.

Although not the trial sponsor, Sanofi worked closely with the German-speaking Myeloma Multicenter Group (GMMG), and “there is potential that Sanofi could work on a filing plan with GMMG in the future,” Zsuzsanna Devecseri, Sanofi’s head of global oncology medical affairs, told Fierce Pharma via email. An October presentation shows the French pharma expects to potentially file Sarclisa for approval in newly diagnosed transplant-eligible myeloma based on GMMG in or beyond 2024.

In the study, 50.1% of patients treated with the Sarclisa combo achieved MRD negativity, while that was the case for 35.6% of RVd patients, meaning patients who got Sarclisa were 83% more likely to hit that marker. MRD is a well-established marker to measure the effectiveness of treatment and a fairly good prognostic factor to predict clinical outcomes.

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The data came from the GMMG-HD7 trial and marks the first time that a phase 3 study reported a better MRD negativity rate postinduction for a CD38 antibody on top of RVd, the investigators noted. The results are presented at the American Society of Hematology's 63rd annual meeting.

But the trial wasn’t all positive. On a secondary endpoint, the rates of complete response were similar between the two arms. Devecseri argued that end of induction is typically too early to detect a significant difference on complete response rates, as eliminating the myeloma protein takes some time.

On Johnson & Johnson’s part, the company has longer-term follow-up for Darzalex’s RVd combo in newly diagnosed transplant-eligible multiple myeloma from the phase 2 Griffin trial. After induction and consolidation treatment, the trial now has two years of maintenance therapy data.

At that evaluation point, the Darzalex-RVd combo maintained a higher MRD-negativity rate of 64.4% compared with 30.1% for RVd, according to data unveiled at ASH 2021. The rates of complete response deepened to 82% for the Darzalex regimen after two years of maintenance, compared with 61% for RVd.

Darazlex-RVd also improved the rates of durable clearance. Among MRD-negative patients, 44% in the Darzelex-RVd group enjoyed that status for at least one year, versus 13% for RVd.

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Craig Tendler, global head of late clinical development of hematology and oncology at J&J’s Janssen, said he wasn’t surprised by Sarclisa’s MRD showing after induction. But it’s really a sustained MRD negativity rate that points to better treatment outcomes for patients, he noted in an interview.

In another showing that gives Tendler more confidence in the ongoing phase 3 trial dubbed Perseus of Darzalex in the same setting is a growing pronounced trend toward improved disease progression for the quadruplet therapy. Although not statistically significant for a small-sized phase 2 trial, Darzalex-RVd cut the risk of progression or death by 54% over RVd after a median follow-up of 38.6 months.

While this round of data for the CD38-RVd combos are from trials in transplant-eligible population, the two CD38 antibodies are also nearing a final showdown in patients who aren’t eligible for transplant.

There, Darzalex’s phase 3 Cepheus trial previously bore a primary completion date in April. An independent data monitoring committee conducted a review at that time and recommended the trial to continue following patients, with the next analysis planned for 2022, Tendler said.

As for Sarclisa, its phase 3 Imroz study for the RVd-Sarclisa pairing was expected to read out this year. But Sanofi recently adjusted the timeline and now plans to have data in the first half of next year.

Darzalex enjoys more than four years of a head start over Sarclisa. The Janssen drug is approved in several combination regimens in different indications including newly diagnosed myeloma. Sarclisa marked Sanofi’s return to oncology with an initial FDA go-ahead last March, but it doesn’t yet have a frontline label.