The annual assembly of the American Society of Scientific Oncology drew greater than 30,000 attendees to San Diego, and extra who participated within the convention nearly, all of them trying to see and listen to the most recent developments in blood cancers and hematological issues.
A number of myeloma is all the time an enormous subject of dialogue on the annual ASH assembly, and developments this yr embrace scientific knowledge supporting using sure therapies in even earlier strains of remedy. On the cell remedy entrance, there may be an ongoing effort to enhance the manufacturability of those remedies. Knowledge had been introduced demonstrating shorter “vein-to-vein instances,” the time from when cells are harvested to when therapeutic cells are infused into the affected person. And in sickle cell illness, encouraging early knowledge had been introduced exhibiting promise for a gene-editing remedy that might provide sufferers a one-time remedy.
We couldn’t catch all the things at what is among the greatest medical conferences of the yr. Right here’s a recap of some highlights from the ASH 2024 assembly:
Motion in A number of Myeloma
—GSK reported Part 3 knowledge that assist bringing the a number of myeloma drug Blenrep again to the market. The newest outcomes present a Blenrep drug routine, as a second-line of remedy, helped sufferers dwell longer in contrast in opposition to a drug routine that features the blockbuster Johnson & Johnson drug Darzalex. These outcomes at ASH comply with a Part 3 knowledge readout earlier this yr exhibiting Blenrep beat a drug mixture that features the Bristol Myers Squibb most cancers drug Pomalyst.
Blenrep received accelerated approval in 2020. GSK withdrew Blenrep from the market after it failed a confirmatory Part 3 examine. However that check evaluated the drug as a monotherapy and as a fifth line of remedy. The Part 3 research which can be a part of regulatory submissions at the moment below evaluate examined the drug together with different a number of myeloma therapies and as an earlier line of remedy. GSK’s plans for the drug embrace a examine underway that might assist increasing the drug’s use to first-line a number of myeloma remedy, the place its competitors will embrace Darzalex.
—Talking of Darzalex, Johnson & Johnson reported knowledge for an injectable formulation of the drug, Darzalex Faspro, as a remedy for smoldering a number of myeloma, which is an asymptomatic precursor to this kind of blood most cancers. In smoldering a number of myeloma, sufferers have excessive ranges of irregular plasma cells and elevated ranges of monoclonal protein within the blood.
In a Part 3 check that enrolled 390 members, J&J’s Darzalex Faspro considerably delayed high-risk smoldering a number of myeloma from progressing to energetic illness. The drug additionally prolonged general survival in comparison with energetic monitoring, which is the present customary of care. Darzalex Faspro at the moment has 9 approvals in a number of myeloma. Final month, the corporate submitted purposes within the U.S. and Europe looking for so as to add smoldering a number of myeloma to the product’s listing of permitted indications.
—Arcellx’s BCMA-targeting cell remedy, anito-cel, posted Part 2 leads to a number of myeloma that analysts say are corresponding to Carvykti from companions Legend Biotech and Johnson & Johnson. It’s the security outcomes that reinforce their view of the Arcellx cell remedy as probably finest in school. Carvykti’s trials confirmed some instances of delayed neurological toxicities, together with parkinsonism, a motion dysfunction. Arcellx is engineered to supply higher security and the outcomes to date present no indicators of parkinsonism. Analysts say Arcellx additionally has benefits by way of its partnership with Gilead Sciences, which has a world cell remedy manufacturing infrastructure and expertise commercializing such merchandise.
—J&J and Legend added to the physique of proof exhibiting that Carvykti helps a number of myeloma sufferers dwell longer in comparison with customary therapies. The Part 3 examine, which examined the cell remedy in sufferers who had obtained one to 3 prior strains of remedy, confirmed that after a median 33.6 months of follow-up, Carvykti led to considerably elevated charges of minimal residual illness negativity, a marker of survival outcomes for a number of myeloma sufferers.
A Have a look at Leukemia & Lymphoma Medicine
—Kura Oncology reported extra detailed knowledge for ziftomenib, a drug candidate now partnered with Kyowa Kirin. The small molecule menin inhibitor is being developed to deal with leukemias pushed by sure genetic mutations. Outcomes from the Part 1 dose-escalation examine confirmed a 100% full response charge in these with NPM1 mutations. In sufferers whose illness harbored KMT2A mutations, the whole response charge was 83%. The businesses mentioned the drug was secure and properly tolerated together with customary of care therapies. Final month, Kyowa Kirin paid $330 million to start the alliance on ziftomenib. If the drug reaches the market, it can compete in opposition to Revuforj, a Syndax Prescription drugs menin inhibitor that received FDA approval in November.
—Eli Lilly drug Jaypirca landed accelerated FDA approval final yr as a remedy for superior instances of mantle cell lymphoma following no less than two prior strains of remedy. On the ASH convention, Lilly reported Part 3 knowledge that might assist full approval for the drug, a small molecule inhibitor of a protein referred to as BTK. Outcomes present Jaypirca diminished the chance of illness development or demise by 46% in comparison with customary remedies. Therapy with the Lilly drug additionally extended the time to the following remedy or demise by a median 23.9 months. Lilly mentioned the security profile of Jaypirca in Part 3 was according to the Part 1/2 check used to assist the drug’s accelerated approval.
—In a pre-planned evaluation of a Part 2 scientific trial in diffuse massive B-cell lymphoma, Merck’s experimental drug zilovertamab vedotin led to a 97.2% full response charge. What saved the examine from reaching the 100% mark was discontinuation of two members by doctor resolution, one affected person every within the middle- and high-dose cohorts. All members within the low-dose group confirmed a whole response.
Based mostly on the scientific trial outcomes for the drug candidate, an antibody drug conjugate (ADC), Merck has chosen the low dose to advance to Part 3 testing. The outcomes to date are encouraging for this remedy and others developed to hunt out ROR1, a novel goal at the moment unaddressed by any permitted medication. Different corporations growing ROR1-targeting ADCs embrace Ipsen, which licensed its candidate from Sutro Biopharma earlier this yr, and CStone Prescription drugs.
Sickle Cell Illness Developments
—Final month, Beam Therapeutics teased encouraging early scientific outcomes for six sufferers dosed with BEAM-101, a gene-editing remedy for sickle cell illness. Up to date knowledge at ASH put some figures to the outcomes as of an Oct. 28 knowledge cutoff. Outcomes confirmed these sufferers achieved fetal hemoglobin ranges exceeding 60% and a discount in sickle-shaped hemoglobin under 40% at month 1. These ranges had been sustained to the final time level obtainable, indicating that the results of the one-time remedy are sturdy to date. The remedy’s security profile was according to that of busulfan, the conditioning remedy that’s used to organize a affected person to obtain BEAM-101. As beforehand reported, there was one fatality from respiratory failure, which investigators attributed to busulfan. In all six sufferers dosed, there have been no severe opposed occasions attributed to BEAM 101.
—Novo Nordisk introduced Part 2 knowledge for etavopivat exhibiting the once-daily oral drug led to a discount in vaso-occlusive crises, a complication of sickle cell illness. The one-year, proof-of-concept examine additionally confirmed a rise in hemoglobin ranges. With these outcomes, Novo Nordisk mentioned it has chosen the dose to check in a Part 3 scientific trial. Etavopivat got here to Novo Nordisk from the $1.1 billion acquisition of Forma Therapeutics in 2022.
Catching Up on Cell Therapies
—The most cancers goal GPRC5D is at the moment addressed by just one FDA-approved drug, the Johnson & Johnson bispecific antibody Talvey, a remedy for a number of myeloma. Bristol Myers Squibb goals to be the primary to drug GPRC5D with a cell remedy. On the ASH assembly, BMS introduced Part 1 knowledge exhibiting its candidate, arlocabtagene autoleucel (arlo-cel), led to sturdy responses that deepened over time. Bristol says these outcomes assist arlo-cel as a possible first-in-class remedy for relapsed or refractory a number of myeloma in closely pretreated sufferers. A Part 2 check of the cell remedy is ongoing.
—Galapagos’s non-Hodgkin lymphoma cell remedy candidate GLPG5101 posted extra Part 1/2 outcomes exhibiting encouraging efficacy and security. The corporate additionally identified that the vein-to-vein time was a median seven days. By comparability, the multi-step manufacturing course of for at the moment obtainable cell therapies can take a month or extra. Galapagos’s course of leverages Cocoon, a point-of-care manufacturing system from contract manufacturing big Lonza.
—Orca Bio posted knowledge for Orca-T, an allogeneic T-cell immunotherapy in testing as a remedy for 3 sorts of blood most cancers: acute myeloid leukemia, acute lymphoblastic leukemia, and high-risk myelodysplastic syndrome. Outcomes from a three-year follow-up evaluation from Part 1b confirmed an general survival charge of 86% for the examine drug in comparison with 67% in a non-randomized historic group that obtained an allogeneic stem cell transplant.
Orca-T is comprised of extremely purified immune cells from donors. Within the Part 1b check, Orca Bio mentioned this allogeneic remedy was manufactured reliably with vein-to-vein time of 72 hours or much less throughout the U.S. An ongoing Part 3 check evaluating Orca-T to standard allogeneic stem cell transplants is anticipated to report preliminary knowledge within the first half of 2025.
A Recap in Uncommon Blood Illness
—Sanofi revealed particulars of its Part 3 check of rilzabrutinib in persistent or power immune thrombocytopenia, a uncommon immune dysfunction resulting in low platelet ranges. Outcomes present the small molecule BTK inhibitor led to platelet response in 65% of sufferers within the examine drug arm in comparison with 33% of those that obtained a placebo. Moreover, a sturdy platelet response was noticed in 23% of sufferers who obtained rilzabrutinib versus zero within the placebo group. The drug, which got here from the $3.7 billion acquisition of Principia Biopharma in 2020, is at the moment below regulatory evaluate within the U.S. and Europe.
—Normal of take care of the uncommon blood dysfunction paroxysmal nocturnal hemoglobinuria (PNH) contains two blockbuster AstraZeneca medication, Soliris and Ultomiris, although Apellis Prescription drugs and Novartis are attempting to take market share with their FDA-approved therapies. Regeneron Prescription drugs goals to compete with these complement inhibitors with a drug mixture: the permitted antibody pozelimab (model identify Veopoz) and the experimental RNA-interference remedy cemdisiran. A Part 3 check is underway testing the mix in opposition to Soliris. At ASH, Regeneron reported knowledge from an exploratory cohort testing the 2 medication in opposition to Ultomiris. Outcomes confirmed the Regeneron drug combo helped sufferers obtain and keep better management over their illness in comparison with Ultomiris.
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