Mazdutide

Takeda's third-quarter pipeline cull, a head-to-head win against Novo Nordisk's semaglutide and a potential $1 billion-plus licensing deal by Roche made our news this week. Takeda tightened its pipeline in the third quarter. Innovent Biologics reported a head-to-head win against semaglutide in a Chinese phase 3 trial. Roche licensed a respiratory bispecific candidate in a potential $1 billion-plus deal. And more.1. Takeda drops AstraZeneca-partnered neurological program after phase 2 failureTakeda’s AstraZeneca-partnered alpha-synuclein antibody, TAK-341/MEDI1341, has failed in a phase 2 study in multiple system atrophy. The Japanese pharma also stopped developing the orexin-2 receptor agonist danavorexton (TAK-925) for narcolepsy “due to strategic considerations,” while phase 2 development in respiratory conditions remains ongoing.2. Innovent, Lilly's mazdutide trumps Novo's semaglutide in head-to-head diabetes, weight loss studyInnovent Biologics’ China-approved mazdutide has topped Novo Nordisk’s 1-mg semaglutide in a Chinese phase 3 trial conducted in patients with early-stage Type 2 diabetes and obesity. A 6-mg dose of the first-in-class GLP-1/glucagon dual receptor agonist outperformed semaglutide on the proportion of patients who met certain blood sugar and body weight benchmarks. The drug is partnered with Eli Lilly in the country.3. Roche pens $1B biobucks deal for Chinese company's respiratory disease bispecificRoche is paying $75 million upfront and committing up to $995 million in milestones to license a long-acting TSLPxIL-33 bispecific from China’s Qyuns Therapeutics. Coded QX031N, the drug holds promise for chronic obstructive pulmonary disease and asthma, according to Qyuns. The long-acting TSLP mechanism last year attracted GSK to a $1 billion buyout of Aiolos, which got its candidate from China’s Jiangsu Hengrui Pharma.4. Merck, Eisai scrap ambitions for Keytruda-Lenvima pairing in liver cancer subtype after survival missMerck & Co. and Eisai’s Keytruda and Lenvima failed to significantly extend patients’ lives when added to standard transarterial chemoembolization in unresectable, non-metastatic liver cancer. The overall survival miss at an interim analysis has led the pair to close the phase 3 Leap-012 trial. While an FDA expansion appears unlikely, the regimen was recently approved in China based on a positive progression-free survival readout.5. Boehringer returns to Kyowa Kirin with €640M pact for preclinical autoimmune moleculeIn a deal worth up to 640 million euros ($743 million), Boehringer Ingelheim has licensed a preclinical program from Kyowa Kirin that the German pharma hopes could become a “first-in-class … treatment of autoimmune diseases.” No details on the drug’s target or specific indications were given.6. WuXi AppTec sharpens focus by selling off China-based clinical research unitsWuXi AppTec is selling its China-based CRO WuXi Clinical and site management organization WuXi MedKey to Hillhouse. With the divestments, the company aims to emphasize its drug discovery, laboratory testing, process development and manufacturing services, according to a securities filing.7. BIO’s John Crowley urges ‘strategic action’ to strengthen FDA amid China’s biotech rise (Testimony before Congress)In a testimony before the Senate Health, Education, Labor, and Pensions Committee, Biotechnology Innovation Organization chief John Crowley called for “proactive, strategic action” to strengthen the FDA to secure “America’s biotech future” amid China’s rapid rise in biotech. His long list of recommendations includes reducing the time, cost and complexity of early drug development and improving the agency’s first-cycle review success rate.Other News of Note:8. Birds, lizards and cats, oh my: FDA blasts generic drug maker Hetero in scathing Form 4839. Roche's Chugai strikes $200M M&A deal to take over IgAN asset in several Asian countries10. Biogen boosts sales outlook on 'resilient' legacy MS franchise as new launches build momentum11. Astellas taps social media star Babs Costello to promote Izervay for geographic atrophy12. Samsung Bioepis gains full rights to Lucentis, Eylea biosimilars from Biogen in Europe (release)

Innovent signed on to license mazdutide in China through a 2019 agreement with Eli Lilly, marking an extension of a decade-long partnership between the two companies. An experimental GLP-1/glucagon (GCP) dual receptor agonist from Eli Lilly and its Chinese partner, Innovent, has bested Novo Nordisk’s reigning GLP-1 semaglutide, in a phase 3 study across both blood sugar and weight loss metrics. The late-stage trial evaluating mazdutide, the world’s first approved GLP-1/GCG, is also the first to pit a drug from the class against semaglutide in a head-to-head comparison, the Suzhou-based drugmaker said in an Oct. 26 press release.Novo markets its semaglutide as injectable Ozempic and oral Rybelsus for type 2 diabetes and as Wegovy for obesity. Innovent pitted a 6-mg dose of mazdutide against a 1-mg semaglutide regimen in its study of 349 Chinese adults with early-stage type 2 diabetes (T2D) and obesity. To qualify for the China-only trial, patients had to have inadequate glycemic and weight control after lifestyle intervention, regardless of whether they were taking standard metformin monotherapy.Mazdutide's performance against Novo's semaglutide allowed the trial to meet its primary endpoint, which looked at the proportion of patients who achieved hemoglobin A1C (HbA1C) or blood glucose levels over 7.0%, as well as body weight reduction of at least 10% from baseline at the study's 32-week mark. Some 48% of patients in the trial's mazdutide group met those blood sugar and weight loss benchmarks, compared to 21% in the semaglutide arm, Innovent said.Mazdutide also had an apparent edge over semaglutide on both blood glucose levels and weight loss separately, helping patients lower their HbA1c by 2.03% and lose 10.26% of their weight from baseline on average. Semaglutide, meanwhile, triggered a 1.84% reduction in HbA1c levels and helped patients achieve an average 6% weight loss.“Treatment strategies that address both glycemic control and weight loss are playing an increasingly critical role in improving clinical outcomes for patients with T2D and comorbid obesity,” principal trial investigator Linong Ji, M.D., explained in the release.Mazdutide, approved in China for weight management and type 2 diabetes, may benefit “a wide range of patients requiring multifaceted improvements in glycemic control, body weight, and cardiometabolic risk factors,” Innovent’s chief R&D officer of general biomedicine, Lei Qian, M.D., Ph.D., added. The drug won its first-in-class approval from China’s National Medical Products Administration (NMPA) in June, marking a breakthrough moment for incretin medicines. Targeting the GCG receptor can increase the body’s energy expenditure and improve hepatic fat metabolism, creating a powerful weight loss mechanism when added to the insulin benefits of GLP-1 agonists. Innovent signed a 2019 agreement with Lilly to license the drug in China, marking an extension of a decade-long partnership between the two companies. Lilly maintains the rights to the mazdutide outside of China, where it has yet to win approval.Mazdutide and semaglutide are also going head-to-head in another ongoing study that compares the medications in obesity accompanied metabolic-associated fatty liver disease. Innovent is planning to further study mazdutide in adolescents with obesity, metabolic dysfunction–associated steatohepatitis (MASH), certain heart failure indications and against Lilly’s tirzepatide in obesity.