Daratumumab/Hyaluronidase-fihj

The FDA has approved Sanofi's Sarclisa as part of a combination in certain patients with newly diagnosed multiple myeloma. Since an initial FDA go-ahead in 2020, Sanofi’s Sarclisa has been specifically approved for patients with previously treated multiple myeloma. That changed Friday.The FDA has approved Sarclisa to be used in combination with bortezomib, lenalidomide and dexamethasone (VRd) to treat patients with newly diagnosed multiple myeloma who are not eligible for stem cell transplant.With the expansion, Sarclisa stands to give Johnson & Johnson’s Darzalex some company in the indication. Since 2018, the J&J med has been the lone CD38 antibody approved for first-line myeloma. For that Darzalex approval, the FDA cleared the med to be paired with bortezomib, melphalan and prednisone, also for transplant-ineligible patients. That Darzalex regimen is considered outdated and not used very often these days. The J&J drug has other combinations approved for first-line use. Before the latest FDA approval, Sarclisa-VRd was recently added to the National Comprehensive Cancer Network (NCCN) myeloma treatment guidelines as a preferred regimen for transplant-ineligible patients, along with VRd alone and a Darzalex-Rd combo. All three regimens bear the highest category 1 recommendation.“We’re getting access to the biggest segment of this market, and we are leveling the playing field in a major class of drug,” Olivier Nataf, Sanofi’s global head of oncology, said in a recent interview with Fierce Pharma.Sarclisa-VRd proved its worth as a new standard of care in the phase 3 IMROZ trial. Compared with VRd alone, the Sarclisa regimen significantly reduced the risk of progression or death by 40% in first-line transplant-ineligible patients. Patients in the VRd arm went a median 54.3 months without disease progression in the study. Although the median progression-free survival (PFS) mark was not yet reached for Sarclisa at the time of the analysis, investigators estimated the number would reach around 90 months.For context, Darzalex-Rd showed a median PFS of 61.9 months, versus 34.4 months for Rd, in an updated analysis of the phase 3 MAIA trial conducted in newly diagnosed transplant-ineligible patients.Darzalex might have its own VRd combination for front-line transplant-ineligible patients in the near future. The phase 3 CEPHEUS trial is evaluating that use with an estimated primary completion date in August 2025. Challenging Darzalex won’t be easy. Worldwide sales of the J&J med jumped 22% and reached $9.7 billion in 2023. By comparison, Sarclisa reeled in $381 million last year thanks to a 30% year-over-year increase. Still, Nataf argued that the market is big enough for Sanofi to make its mark.The CD38 class is expected to reach $15 billion in annual revenue by 2028, Nataf said, citing a forecast by Evaluate.“We are one of only two,” Nataf said.While Sarclisa-VRd in transplant-ineligible patients marks the Sanofi drug’s first front-line nod, Sanofi is progressing toward even broader indications.In a German study coded GMMG-HD7, Sarclisa’s combination with VRd significantly improved PFS compared with VRd alone in transplant-eligible newly diagnosed myeloma, Sanofi said in August. The study is meant to support applications for regulatory approvals, and Sanofi plans a U.S. filing in the first half of 2025, according to the company's most recent quarterly update. NCCN guidelines just added that combo as an “other recommended regimen” in first-line transplant candidates. Darzalex-VRd is the preferred regimen there.There’s also a combination of Sarclisa with Amgen’s Kyprolis, lenalidomide and dexamethasone (KRd). In the phase 3 IsKia trial, the Sarclisa-KRd regimen helped significantly more first-line transplant-eligible patients achieve a deep tumor clearance threshold known as minimal residual disease negativity. Although Sanofi has not announced a regulatory plan for that use, the FDA appears poised to allow minimal residual disease as a surrogate endpoint to enable accelerated approvals for new myeloma therapies. Experts on an advisory committee unanimously backed the establishment of that surrogate endpoint in April after two separate meta-analyses of past clinical trials suggested it could predict longer-term outcomes such as PFS. Meanwhile, J&J has been switching patients to a subcutaneous formulation of Darzalex called Darzalex Faspro and is using it in clinical trials for new combinations, such as one with VRd in transplant-eligible patients.Sanofi is developing its own subcutaneous Sarclisa, with a readout from the IRAKLIA trial in the second-line setting expected this year. Besides administering Sarclisa under the skin through a syringe pump, the French pharma is working on an on-body delivery system, which would “make the life of nurses, patients and outpatient clinics easier,” Nataf said.Editor's Note: The story was updated to add some information about J&J's CEPHEUS trial.

The approval comes a year after manufacturing revisions postponed an initial FDA decision. It’s better late than never for an FDA approval for the first subcutaneous PD-L1 inhibitor, which was doled out to Roche’s Tecentriq Hybreza after manufacturing delays derailed the company's initial launch plans last year.The agency was originally slated to issue its verdict on Tecentriq in its under-the-skin formulation last September but the drug’s manufacturing processes needed updating, Roche’s delivery technology partner Halozyme Therapeutics said in a filing at the time. The tweaks, which a Roche spokesperson said were made in response to the FDA’s evolving requirements, were expected to wrap up in 2023 to support a 2024 launch. The world-first approval for the formulation came in the U.K. last year. Now, the therapy has been cleared for use in the U.S. in all of the Tecentriq adult formulation's indications, including types of lung, liver, skin and soft tissue cancers. The new version uses Halozyme’s Enhanze drug delivery tech to subcutaneously inject the product over seven minutes, compared to the 30 to 60 minutes needed for an IV infusion.“By enabling subcutaneous administration for a cancer immunotherapy, Tecentriq Hybreza now offers patients with multiple cancer types and their physicians greater flexibility and choice of treatment administration,” Roche’s chief medical officer and head of global product development Levi Garraway, M.D., Ph.D., said in a press release. In a phase 2 study, 71% of patients preferred the subcutaneous version over the standard formulation, with many citing increased comfort during treatment, less time in the clinic and reduced emotional distress. Roche reported that 79% of patients who tried both formulations opted to continue their treatment with Tecentriq Hybreza.Halozyme’s Enhanze technology is based on a proprietary recombinant human hyaluronidase enzyme, which allows the therapy to more quickly disperse and absorb into the bloodstream. The delivery tech has played a part in improving ease of administration for other big-name cancer therapies such as Johnson & Johnson’s Darzalex Faspro and potentially Bristol Myers Squibb’s Opdivo, which has yet to receive approval as a subcutaneous option. While Tecentriq Hybreza has now beat Opdivo to the punch as the first subcutaneous checkpoint inhibitor cleared by the FDA, the agency’s verdict on the new Opdivo formulation is expected to come later this year.Tecentriq was first approved in 2016 and took home CHF 3.77 billion ($4.44 billion) in 2023 sales. In areas crowded with formidable rivals such as Merck’s Keytruda in non-small cell lung cancer (NSCLC), Roche is “still holding our own” in the U.S., pharma chief Teresa Graham said on a February conference call.