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With Carvykti (ciltacabtagene autoleucel) producing "science fiction-like" efficacy, Johnson & Johnson is pulling back the curtain on another CAR-T therapy — one that targets two antigens simultaneously. The company on Friday provided a first look at clinical data for JNJ-4496, an investigational dual-targeting therapy that binds CD19 and CD20 antigens on malignant B-cells.JNJ-4496, formerly known as C-CAR039, incorporates a 4-1BB costimulatory domain intended to enhance binding strength and persistence while potentially addressing common resistance mechanisms. J&J acquired rights to the asset in 2023 through a $245-million upfront deal with Cellular Biomedicine Group, since renamed AbelZeta.Presented at the European Hematology Association (EHA) conference, the Phase Ib study is evaluating JNJ-4496 in patients with relapsed or refractory large B-cell lymphoma (LBCL) who have not previously received CAR-T cell therapy.Among 22 evaluable patients treated at the recommended Phase II dose of 75 million CAR-T cells, those who had received only one prior line of therapy (n=10) achieved an objective response rate (ORR) of 100% after a median follow-up of four months, with 80% reaching a complete response. The remaining 12 who had undergone two or more prior therapies showed a 92% ORR, with 75% achieving a complete response.Safety data from 25 patients in the recommended dose cohort showed no cases of Grade 3 or 4 cytokine release syndrome. Two patients experienced immune effector cell-associated neurotoxicity syndrome (ICANS), including a Grade 1 event as well as a Grade 3 event in a patient with central nervous system lymphoma. The most common severe side effect was neutropenia, occurring in 72% of patients."As we continue to unlock the full potential of CAR-T cell therapies through novel next-generation approaches, these promising data reinforce earlier long-term findings and highlight the potential of JNJ-4496 to improve outcomes for patients," commented Jeffrey Infante, the company's vice president of early clinical development and translational research.The lymphoma results come as J&J basks in Carvykti's momentum. At the recent American Society of Clinical Oncology (ASCO) meeting, the company presented long-term data for the BCMA-directed CAR-T, which is partnered with Legend Biotech, showing that 33% of heavily pretreated multiple myeloma patients remained progression-free for at least five years following a single CAR-T infusion, with no subsequent treatment. For more, see – Spotlight On: With GSK's Blenrep waiting in the wings, J&J touts game-changing Carvykti data.J&J also reported initial Phase I results at ASCO for JNJ-5322, a trispecific antibody targeting CD3, BCMA and GPRC5D that achieved an ORR of 86.1% in relapsed multiple myeloma among the 36 patients who received the recommended Phase II dose. Findings from the study will also be presented at EHA.

With multiple positive trials in the books, GSK is working through a global return to market for antibody-drug conjugate Blenrep. GSK is putting the finishing touches on its case for antibody-drug conjugate Blenrep with a key progression-free survival (PFS) readout ahead of its potential U.S. return in multiple myeloma this summer.The data, presented Thursday at the European Hematology Association (EHA) 2025 Congress, help further fill in the efficacy picture for the drug. The results are from the company’s DREAMM-8 study in patients with relapsed or refractory multiple myeloma (RRMM) who had previously tried at least one prior line of therapy, including Bristol Myers Squibb’s Revlimid (lenalidomide).At last year’s American Society of Clinical Oncology (ASCO) annual meeting, GSK revealed that Blenrep, combined with Bristol Myers Squibb’s Pomalyst and the corticosteroid dexamethasone (PomDex), slashed the risk of disease progression or death by 48% compared with Takeda’s Velcade and PomDex. At the time, the Blenrep arm of the study hadn’t yet reached a median PFS. Now, after an additional eight months of follow-up, investigators report that patients treated with Blenrep and PomDex lived without their disease getting worse for a median of 32.6 months. Those taking the Velcade-based version of the regimen experienced 12.5 months of median PFS. At 18 months of treatment, the estimated PFS rate was 63% for Blenrep versus 41% for the comparator arm.The findings mirror those from GSK’s previously reported DREAMM-7 study, which pitted Blenrep against Johnson & Johnson’s Darzalex. That trial yielded a 36.6-month median PFS for Blenrep compared to 13.4 months for Darzalex. In that study, both agents were combined with Velcade and dexamethasone.Put together, the two studies demonstrate the “consistency” of Blenrep’s strong ability to drive PFS, even in different combinations, GSK’s global head of oncology R&D Hesham Abdullah, M.D., told Fierce Pharma at the recent ASCO annual meeting in Chicago.“In both instances, we’re seeing such great magnitude of effect,” Abdullah said.Of course, the overall survival data from DREAMM-7 help further make Blenrep’s case. In December, GSK reported that Blenrep and its Velcade-dexamethasone combo reduced the risk of death by 42% over the Darzalex-based regimen, with a three-year survival rate of 74%. The outcomes from DREAMM-8 and DREAMM-7 have so far supported regulatory approvals for Blenrep in both its Velcade and Pomalyst combinations in the U.K., Japan and Europe. The FDA is set to decide on the drug combos by July 23.A U.S. approval would signal a major comeback for Blenrep. After winning an accelerated approval from the FDA in 2020 as a monotherapy in heavily pre-treated RRMM patients, GSK pulled the drug from the market two years later after coming up short in a confirmatory study called DREAMM-3. That failed study, while it missed its endpoint, did at least allow the company to learn “a whole lot” about the drug and response it elicits, Abdullah explained. Now, with Blenrep embarking on a different path as a combination therapy in earlier treatment lines, Abdullah can look back at the ADC’s journey thus far as “a process where science and data ultimately prevail.”New and old competition  Still, the competitive landscape looks different now than when Blenrep made its initial exit. While Abdullah acknowledges that it's been “great” to see the advances made in the disease space over the past few years, the exec remains confident GSK’s offering has an important role to play. If it does hit the market, BCMA-directed ADC Blenrep will compete with J&J and Legend Biotech’s BCMA CAR-T therapy Carvykti in second-line treatment, while Bristol Myers Squibb’s rival CAR-T Abecma and several newer bispecific therapies are vying for share in later-line settings.Despite the hefty competition, many currently approved treatments are administered in hospitals and therefore “not available to all patients,” Abdullah said, pointing to the distribution of multiple myeloma patients in the U.S. About 70% of patients are seen in “community settings,” while the remaining 30% receive treatment at academic sites such as university hospitals.“All in all, it's an accessible drug,” Abdullah summed up. “It delivers robust efficacy, has a manageable safety profile, and is going to be available to all patients, whether they be in an academic setting or, more specifically, the majority of patients that are in that community setting where it can be administered on an outpatient basis.”While Blenrep carries some safety concerns, such as a link to ocular toxicity that previously earned it a boxed warning from the FDA, rival medicines in the space each come with “certain and unique” side effect profiles. GSK, meanwhile, has an “appropriate plan” for managing the eye-related side effects associated with Blenrep treatment, Abdullah said. The company has kept a concentrated focus on potential visual acuity impacts through patient reported outcomes, for example. GSK expects that Blenrep could reach peak annual sales of more than 3 billion pounds sterling (about $4 billion). The drug’s pending market reentry also gave GSK confidence to boost its 2031 sales target to more than 40 billion pounds, despite uncertainties around the company’s flagship vaccines business.

iStock, siraanamwong J&J has a multi-year head start, but Gilead believes it can win market share by delivering a drug with better safety and at least as good efficacy. Johnson & Johnson may face a new challenge to its burgeoning BCMA CAR T cell therapy empire. Having come from behind to capture the market from Bristol Myers Squibb, J&J is now preparing for the arrival of a fresh threat from Gilead’s anitocabtagene autoleucel (anito-cel). Gilead is targeting a 2026 launch for a cell therapy that it believes could expand the CAR T multiple myeloma market through outpatient use. Billions of dollars are on the line. Carvykti sales hit $963 million last year and, having jumped more than 100% to $369 million in the first quarter, are on track to pass the blockbuster threshold this year. Visible Alpha’s consensus analyst estimate puts peak sales at around $7 billion in 2030. Gilead has put a higher value on the overall CAR-T multiple myeloma market. Talking at a Leerink event in March, Cindy Perettie, global head of Gilead’s CAR-T unit Kite, predicted the market will be worth $15 billion to $20 billion in 2034. The forecast makes multiple myeloma a bigger opportunity for Gilead than its current CAR-T stronghold in lymphoma, which Perettie forecast will grow to between $10 billion and $12 billion. J&J has a multi-year head start, having first won FDA approval for Carvykti in 2022, but Gilead believes it can win market share by delivering a drug with better safety and at least as good efficacy. Manufacturing is the third piece of the plan, with Gilead using the infrastructure set up for its other CAR T cell therapies as a competitive advantage. How Gilead Is Positioning Anito-cel In May, Gilead’s anito-cel partner Arcellx shared updated Phase II data on the cell therapy as a fourth-line or later treatment for relapsed or refractory multiple myeloma. The overall response rate in the 117 patients was 97%. Almost 70% of patients had a complete response. BMO Capital Markets analyst Evan David Seigerman said in note to investors that “anito-cel continues to demonstrate meaningful efficacy that is at a minimum comparable to Carvykti, with potentially better [overall survival] rates.” Seigerman compared anito-cel’s 12-month overall survival rate, 95%, favorably to the 89% rate in a Carvykti study. Gilead’s belief that anito-cel may have a safety advantage rests on the relatively low rates of neurotoxicity seen in patients to date. Carvykti has a boxed warning for potentially life-threatening adverse events including Parkinsonism and Guillain-Barré syndrome. As of the May 1 data cutoff, no patients in the anito-cel trial had Parkinsonism, cranial nerve palsies, Guillain-Barré or immune-mediated enterocolitis. Seigerman said the absence of delayed neurotoxicity “continues to increase our confidence in anito-cel’s safety profile.” The analyst cited the 1% rate of grade 3 or above cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS), both of which are on Carvykti’s boxed warning, as another positive. Perettie discussed the implications of the CRS and ICANS rate at a RBC Capital Markets event in May. The Gilead executive said only one in 10 multiple myeloma patients who are eligible for CAR-T currently receive a cell therapy. Patients who do receive CAR-T are admitted to hospital for four to five days, Perettie said. Gilead sees eliminating hospital stays as a way to increase uptake of CAR-T among eligible patients. “We now know some of the pieces that are going to help move that market, which is how we get closer to patients in the community,” Perettie said. “Ninety percent of myeloma patients sit in the community, only 10% in academic centers. Because it’s a more indolent disease, they don’t get referred to later and so reaching them where they are is important.” Around 10% of patients in the Phase II trial have received anito-cel in an outpatient setting, Perettie said. Gilead has increased the proportion of outpatients in its Phase III trial to 20%. The company plans to use a network of more than 550 authorized treatment centers that it has built up globally for its other CAR-T therapies to complement the outpatient option. Gilead created the network to support its lymphoma cell therapies Yescarta and Tecartus. The biotech also plans to use the manufacturing capabilities it built for Yescarta and Tecartus to produce anito-cel and gain an edge over its rival. Gilead believes that the manufacturing network is a differentiator, reflecting the challenges of producing CAR-T therapies using a patient’s own cells, CEO Daniel O’Day explained at a Bernstein event in May. “We have the largest manufacturing network, the shortest turnaround time. You need to have a short turnaround time because people are put in an immunocompromised state while they’re waiting for their cells to come back, and you want to make sure you get those back as quickly as possible so you get the best clinical benefit,” O’Day said. The Case for Carvykti BMO analyst Kostas Biliouris has pushed back on the idea that cross-trial comparisons show anito-cel is safer and more effective than Carvykti. Writing in a note to investors, Biliouris said there are “significant differences” in the populations enrolled in anito-cel and Carvykti trials that could confound comparisons. Three times higher corticosteroid use for CRS management in the anito-cel trial “further precludes direct . . . efficacy/safety comparisons,” the analyst said. Biliouris quoted real-world data and post-hoc analyses that suggest corticosteroid use could contribute to seeming differences in the safety and efficacy of the CAR T cell therapies. Biliouris is bullish on Carvykti, reflecting the fact that J&J and partner Legend Biotech have shown statistically significant improvements in overall survival and are increasing use in earlier treatment lines. The FDA has approved Carvykti for second-line use . Gilead’s Phase III trial is enrolling patients who have tried one to three prior lines of therapy, including an anti-CD38 antibody and an immunomodulatory drug. The analyst also cited Carvykti’s “differentiated [seven-day] CRS onset that facilitates outpatient dosing” as a strength of the cell therapy. J&J is running two trials that are allowing people to receive Carvykti as an outpatient. Patients initially stay within 30 minutes of the hospital but are admitted as inpatients on day five of the studies, reflecting knowledge of the timing of CRS and other adverse events. Gilead’s outpatient offering may prove more flexible and attractive to patients, but in J&J it will face a deep-pocketed incumbent that is leveraging its head start to expand and entrench the use of Carvykti.