Daratumumab

Johnson & Johnson has announced that its Darzalex Faspro-based regimen (daratumumab and hyaluronidase, in combination with bortezomib, lenalidomide and dexamethasone (D-VRd)), has received approval from the US FDA to treat adults with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant (ASCT). The approval is based on results from the phase 3 CEPHEUS study, which compared the safety and efficacy of the D-VRd regimen with bortezomib, lenalidomide and dexamethasone (VRd) alone. Almost five years later, the Darzalex Faspro-based regimen showed significantly increased rates of complete response or better at 81.2% vs 61.6% with VRd. The study showed that the safety profile of the Darzalex Faspro-based regimen was favourable, with the most common adverse events including upper respiratory tract infection, sensory neuropathy and musculoskeletal pain. Multiple myeloma is a blood cancer affecting plasma cells. It is the second most common blood cancer globally. Estimates suggest that over 36,000 people will be diagnosed with multiple myeloma in the US, with over 12,000 deaths in 2026. Multiple myeloma has an average five-year survival rate of 59.8% and is currently incurable. Darzalex Faspro received approval from the FDA in May 2020, and is already approved for eleven indications in multiple myeloma. June Lanoue, US president, haematology at Johnson & Johnson, said: “This approval marks the twelfth indication for Darzalex Faspro overall and fifth in newly diagnosed multiple myeloma, underscoring its role as foundational therapy for both newly diagnosed and relapsed/refractory patients. “CEPHEUS demonstrated the efficacy of [D-VRd] as a frontline standard of care. With this approval, patients can receive D-VRd when they are first diagnosed with multiple myeloma, an important milestone as we work to one day deliver a functional cure.”

A new approval marks Darzalex Faspro's 12th indication and its fifth in the newly diagnosed multiple myeloma setting. Even as Johnson & Johnson’s oncology superstar Darzalex Faspro racks up megablockbuster sales and reshapes the multiple myeloma treatment paradigm, the drug is still finding ways to consolidate its position. This week, the drug is doing just that with an FDA nod for a more powerful regimen in newly diagnosed patients who are ineligible for autologous stem cell transplant.The Jan. 27 approval enables Darzalex Faspro’s use within a quadruplet combination that includes Takeda’s Velcade, Bristol Myers Squibb’s Revlimid and the steroid dexamethasone (VRd), which is altogether referred to as D-VRd. Before that, the triplet regimen of D-Rd has been allowed to treat first-line, transplant-ineligible patients since 2019. D-VRd is now the only anti-CD38 antibody-based regimen that can treat newly diagnosed patients regardless of transplant eligibility, J&J said in a Jan. 27 press release.Having secured a nod for those who are transplant-eligible in 2024, the new approval rounds out D-VRd’s approved uses within the newly diagnosed patient pool. It’s Darzalex’s 12th indication overall and its fifth in the newly diagnosed multiple myeloma setting, “underscoring its role as foundational therapy for both newly diagnosed and relapsed/refractory patients," J&J’s U.S. president of hematology, June Lanoue, commented in the company release.In the Cepheus trial that supported the nod, 395 patients who were ineligible for or refused a transplant as their initial therapy were randomized to D-VRd or VRd on its own. The company primarily weighed the treatment’s impact using a minimal residual disease (MRD) negativity rate, which is a “potential predictor of prolonged progression-free and overall survival,” principal investigator Saad Z. Usmani, M.D., noted in J&J’s release. At a median follow-up of 22 months, the overall MRD-negativity rate at a sensitivity of 10-5 (meaning no cancer cells detected within 100,000 bone marrow cells) came out to 52.3% for those in the treatment arm compared to 34.8% observed among those on VRd. By 39 months, the proportion of patients who sustained MRD negativity for more than 12 months was at 42.6% for the quadruplet versus 25.3% for the triplet, J&J said.The Darzalex-based regimen was also shown to cut down the risk of disease progression or death by 40% over VRd alone. Outcomes from a median follow-up of 59 months (4.9 years) showed that the quadruplet treatment “significantly increased” the depth of response achieved, J&J said, although overall survival data were not yet mature at that time.Importantly, the new nod makes D-VRd the first quadruplet regimen the FDA has approved based on a study using MRD-negativity as its primary endpoint, Usmani added. J&J’s use of MRD could help clear the way for others to further incorporate the endpoint in multiple myeloma studies, especially since the FDA issued a draft guidance laying out its recommendations for clinical trial designs involving MRD just last week.  Darzalex Faspro is the subcutaneous offspring of 2015-approved Darzalex, and, together, the Darzalex franchise has been J&J’s stalwart oncology growth driver. The latest nod for the multiple myeloma drug comes a few months after the drug earned the title of the first treatment approved to treat patients with smoldering multiple myeloma, a classification that impacts about 15% of new myeloma diagnoses.J&J’s Darzalex franchise was its top earner by far in 2025 with full-year sales of $14.4 billion, solidifying its starring role in helping the company meet its goal of $50 billion in oncology sales by the end of the decade. These days, much attention toward Darzalex revolves around its proposed combination with J&J’s bispecific Tecvayli in previously treated multiple myeloma. After the company unveiled what it called “unprecedented” phase 3 results for Darzalex-Tecvayli, the FDA “proactively” granted J&J a Commissioner’s National Priority Voucher in December to ensure a speedy regulatory review. The voucher marked the 16th doled out since the FDA introduced the pilot program last year and speaks to the combo's “outstanding trial results,” FDA Commissioner Martin Makary, M.D., said in a statement at the time.