Potential antibody therapies from AstraZeneca and Regeneron for light chain (AL) amyloidosis had new data at ASCO, raising the prospect of new treatments for the rare bone marrow disease.
In AL amyloidosis, abnormal plasma cells in the bone marrow produce misfolded proteins that clump together clump together into amyloid fibrils that are deposited in organs and tissues, causing damage and a wide range of debilitating symptoms.
Standard treatment is designed to destroy the abnormal plasma cells with regimens based on Johnson & Johnson's Darzalex Faspro (daratumumab) and Takeda's Velcade (bortezomib), to prevent the production of the fibrils.
AstraZeneca's anselamimab is designed to work in AL amyloidosis differently, clearing already-formed fibrils, rather than the cells that produce them, a mechanism that was scrutinised in the phase 3 CARES trial.
In CARES, newly diagnosed patients planning standard first-line plasma cell-targeting treatment with Velcade, cyclophosphamide, and dexamethasone were randomised to receive either anselamimab or placebo once weekly for the first four weeks and then every two weeks, as an add-on for the remainder of the study.
The headline news is that anselamimab did not meet the primary endpoint, a combination of time to all-cause mortality (ACM) and frequency of cardiovascular hospitalisations (CVH), compared to placebo in the overall study population.
It was a different outcome in a subcategory of patients with AL amyloidosis associated with kappa light chains, rather than the more common lambda light chain type. In this group, which accounts for 20% to 25% of all cases, anselamimab improved survival by 62%, as measured by ACM, and reduced the frequency of CVH by 71% compared to placebo.
The results, simultaneously published in ASCO's Journal of Clinical Oncology and presented at the show, reveal a strong efficacy signal that has biological plausibility in kappa AL amyloidosis.
"People living with advanced AL amyloidosis often face persistent, progressive, and debilitating organ damage with no available options to target and clear existing amyloid fibril deposits," said CARES principal investigator Ashutosh Wechalekar of University College London.
"Anselamimab has the potential to offer a novel, clinically meaningful therapeutic for this subgroup of patients with kappa AL amyloidosis who can be easily identified by simple, routinely-used diagnostics," he added.
Regeneron's BCMAxCD3 bispecific antibody Lynozyfic (linvoseltamab), already approved to treat relapsed or refractory multiple myeloma, showed a near 100% haematologic complete response rate (CRR) at the highest dose tested (240 mg) in the phase 1/2 LINKER-AL2 study as a second-line or later treatment for AL amyloidosis that has progressed after frontline anti-plasma cell therapy.
In the lower-dose 80 mg group, 100% of patients achieved a very good partial response (VGPR) or better, while the CRR was 71%, and both arms showed "rapid and deep" reductions in light chain fibrils, as well as preliminary signs of improvements in kidney and heart function.
LINKER-AL2 investigator Hans Lee of the Sarah Cannon Research Institute told ASCO that the data supports further development of Lynozyfic in AL amyloidosis.
"The stark reality for patients with systemic AL amyloidosis facing relapsed or refractory disease is that there are no approved treatment options for them," he added. "We look forward to the data maturing to better understand if these results can be maintained and translate to further organ improvement."
https://pharmaphorum.com/news/asco26-could-al-amyloidosis-see-new-crop-therapies
Eli Lilly’s late-spring dealmaking spree shows no sign of stopping as the pharma giant stuck a licensing agreement with South Korean biotech Hanmi Pharm worth up to $1.2 billion for access to a potential next wave of metabolic drugs.
Under the deal, Lilly will help develop Hanmi’s Phase 2 GLP-2 agonist sonefpeglutide with exclusive rights to manufacture and sell the therapy everywhere except Korea. Hanmi plans to complete the ongoing mid-stage study in short bowel syndrome while Lilly will “explore additional clinical trials for sonefpeglutide” based on existing data, according to a press release.
The deal includes an upfront payment of $75 million with the rest of the $1.2 billion subject to the achievement of certain milestones.
A rare disease that affects newborns as well as adults who have undergone gastrointestinal surgery, short bowel syndrome limits the absorption of nutrients in a shortened or damaged small intestine. Hanmi’s GLP-2 sonefpeglutide is designed to promote intestinal growth, reduce inflammation, and protect and regenerate the intestinal mucosa.
If sonefpeglutide eventually reaches the market, it wouldn’t be the first GLP-2 to do so, owing to the 2012 approval of Takeda’s Gattex, also for short bowel syndrome. Zealand Pharma also attempted to break into the space, only for its GLP-2 candidate glepaglutide to be rejected by the FDA in 2024.
Hanmi credits its protein and peptide discovery platform Lapscovery for sonefpeglutide’s progress. The company has used the platform to develop the white blood cell booster Rolvedon that was approved in 2022 and has five other clinical programs making use of the technology.
Lilly, which leads the GLP-1 weight loss space with blockbusters Zepbound and Mounjaro plus recently approved oral Foundayo and the standout investigational triple-agonist retatrutide, has expanded into gastrointestinal indications like Crohn’s disease and ulcerative colitis. The Hanmi deal marks another step in that direction with sights set on short bowel syndrome.
Swimming in weight loss drug earnings, the U.S. pharma giant has been on the hunt for pipeline candidates across a wide range of therapeutic areas, as witnessed through a series of deals over the course of the last few months. A trilogy of vaccine agreements in May added up to a combined value of $3.8 billion. And the company has struck no fewer than five oncology deals so far this year, reflecting an R&D–focused growth mindset and an urge to bring a new generation of treatments to the market.
“It is highly meaningful that Lilly—one of the most closely watched innovators globally—has recognized the development potential for sonefpeglutide,” Hanmi Vice Chairman Jhuyun Lim said in a statement.
https://www.biospace.com/deals/lilly-maintains-deal-streak-with-1-2b-pact-for-hanmis-glp-2-candidate
Servier is buying Edgewise Therapeutics’ muscular dystrophy business for up to $2.65 billion, the second multi-billion-dollar rare disease deal from the French pharma this year after snapping up Day One Biopharmaceuticals in March.
Servier will pay $1.55 billion upfront with $1.1 billion down the line in potential milestone payments to gain access to Edgewise’s fast skeletal myosin inhibitor sevasemten and related capabilities, according to Servier’s Monday morning release.
The drug is being tested in the Phase 3 GRAND CANYON trial for Becker muscular dystrophy (BMD) and in Phase 2 for Duchenne muscular dystrophy (DMD). Both diseases are X-linked genetic disorders that cause progressive loss of muscle function, with DMD characterized as more severe with a life expectancy of about 30 years, according to Servier.
In March, Edgewise presented data at the Muscular Dystrophy Association meeting showing the potential for improved functional performance on sevasemten. If ultimately approved, the therapy would be the first available for BMD. DMD, on the other hand, has some limited options including products from Sarepta Therapeutics, but plenty of unmet need remains in the space.
“This transaction is designed to place the program in the hands of an organization with the experience and infrastructure to support its continued development for people living with Becker and Duchenne muscular dystrophies,” Edgewise CEO Kevin Koch said in a statement.
This is the second time this year Servier has struck an acquisition in the neuro space after buying all of Day One a few months ago. That transaction, worth $2.5 billion, centered on the FDA-approved pediatric brain cancer asset Ojemda.
Servier is focused on oncology, neurology and cardiometabolic diseases.
With the muscular dystrophy business gone, Edgewise will center its efforts around its cardiovascular programs, with proceeds from the Servier transaction fully funding hypertrophic cardiomyopathy asset EDG-7500 through potential approval, according to a separate release from Edgewise.
Stifel declared the deal “surprising—and very favorable.” Truist Securities called it “a good deal,” providing Edgewise with non-dilutive capital and sharpening the pipeline.
The biotech’s shares rose more than 15% to $39.53 as the markets opened Monday.
Edgewise’s cardiovascular work had been investors’ focus anyway, with “sevasemten either under the radar or met with skepticism,” Truist noted. The firm believes the BMD indication could achieve worldwide unadjusted peak sales of $1 billion but provided no estimate for DMD.
“Given the focus on EDG-7500, sevasemten has gotten little attention and we think generally many (including us) were relatively skeptical on BMD,” Stifel wrote. “As such, $1.55B upfront (with none of the clinical risk) is a big win and ascribes more value than what we think was in the stock.”
Last year, the FDA declined to review an early application for sevasemten based on data from the Phase 2 CANYON study.
Twelve-week data from the Phase 2 CIRRUS-HCM trial of EDG-7500 are due in the second quarter of the year, Edgewise reported on Monday. These data are expected to inform the company’s Phase 3 plans, with a trial set to initiate in the fourth quarter.
The company is also working to initiate a Phase 2 trial of EDG-15400 in heart failure with preserved ejection fraction.
With the riskier sevasemten program out of the way, Stifel now believes Edgewise has been tidied up for a potential acquirer interested in the cardiovascular programs.
