Ponsegromab

BARCELONA — One of this weekend’s sleeper data presentations at Europe’s biggest oncology conference puts Pfizer in a leading position in a common cancer condition with no approved treatments in the US or Europe. The New York-based pharma giant’s GDF-15-directed monoclonal antibody helped cancer patients gain weight and, at the highest dose, experience improvements in appetite, physical activity and muscle mass in a Phase 2 trial, according to data presented at the European Society for Medical Oncology confab on Saturday. Analysts at Leerink Partners think the experimental medicine, code-named ponsegromab, has blockbuster potential. But the large pharma has many questions to work through before it can mount a registrational study next year for ponsegromab in cancer cachexia, a muscle-wasting condition that leads to severe weight loss and impacts a patient’s ability to tolerate cancer medications. Patients with cachexia also require more healthcare resources, leading to a “high clinical and economic burden,” according to another Pfizer-funded study presented at ESMO. Doctors have long sought a treatment for the metabolic condition, which some research suggests may be linked to up to 30% of cancer deaths. It’s also a strain on patients with chronic conditions like heart failure and chronic obstructive pulmonary disease, among others. The broad potential gives ponsegromab a shot at achieving sales of $1 billion or more, Leerink Partners analyst David Risinger wrote in a Sunday evening note. Despite its prevalence, though, the condition has not received “the attention it deserves,” Min Li, a professor and co-leader of the cancer biology program at the Stephenson Cancer Center in Oklahoma, said in an email. “We are now more confident in saying that we can see the light at the end of the tunnel,” Li said in the days after the ESMO presentation and simultaneous publication of the Phase 2 data in the New England Journal of Medicine . Having one of the world’s biggest pharma companies with ample R&D resources to approach late-stage testing could be a boon for the field. “Incredible progress is finally being made in this space, and we very much hope that Pfizer’s findings continue to be positive and pave the way for more successful trials to follow,” Andy Judge, a University of Florida professor and president of the Cancer Cachexia Society, told Endpoints in an email. Cachexia comes with a lot of complexities, likely leading to a challenging Phase 3 showdown for Pfizer. The company anticipates launching the trial next year and it still needs to hash out plans with regulators, according to a spokesperson, who said Pfizer will share more Phase 3 details at a later date. The condition is quite heterogeneous and impacts different cancers at varying rates, which could make it difficult to prove a treatment works in late-stage trials. Li noted that “there is no consensus on the optimal endpoint to evaluate cancer cachexia.” Another biotech, NGM Bio, warned in recent years of the lack of a clear regulatory path for cachexia. Another company received approval in Japan in 2020 for the medicine anamorelin, but the ghrelin receptor agonist was rejected in Europe a few years before. Also standing in the way is the number of organs and tissues involved in the systemic dysfunction. Going after a single pathway “has yielded limited efficacy,” Li said. Pfizer’s ponsegromab goes after growth differentiation factor 15, or GDF-15. The company’s researchers have said neutralizing GDF-15 could lead to improvements in caloric intake and boost physical activity. The candidate was discovered in-house and first entered the clinic in a 2018 healthy volunteer trial. Ponsegromab is also being tested in patients with heart failure . That study is enrolling patients with cardiac cachexia or fatigue in its main cohort and is expected to be completed next March, according to the federal trials database. Li noted other potential pathways in cancer cachexia could be targeted, such as “myostatin/activin signaling, IL-6, ghrelin, circular RNAs, metabolic enzymes, TNF and TGF.” Meanwhile, more studies are needed to “directly prove” that stabilizing muscle and fat reserves, “or even revers[ing] those losses,” has a direct impact on patient outcomes, Michael Rosenthal, assistant director of radiology at Dana-Farber/Brigham and Women’s Hospital, said in an email. Aside from the effects on weight, doctors will look for impacts on daily activities. “It would be impressive to see improvement in ECOG performance status and overall survival in a randomized trial of chemotherapy with or without ponsegromab,” Vincent Chung, a medical oncologist at City of Hope, said in an email. ECOG is a scale that assesses a patient’s ability to function, including walking and self-care activities. Pfizer is in the lead in cachexia drug development, and it’s no stranger to breaking open fields, having done so in areas like ATTR-CM, where it could soon face competition. Other drugmakers looking at cachexia include UK-based Actimed Therapeutics, Tokyo-based TMS and Vistagen, which says on its website that it is “evaluating the path forward” for its candidate for more Phase 2 development. Even if those medicines make it to market, it’s still important to think about treating cachexia in a “multi-dimensional way, rather than a single drug,” David Hui, director of supportive and palliative care research at the University of Texas MD Anderson Cancer Center, said in an interview on the sidelines of ESMO. Doctors currently work with a team of healthcare professionals to address cachexia with diet and exercise and medications to treat symptoms of pain, difficulty swallowing and other complications, he said. “Having the dietitian, physical therapy and supportive palliative care team working side by side together with the patient and family can, hopefully, lead to improved outcomes because everyone may have different concerns related to cachexia,” Hui said.

Over the weekend at the European Society for Medical Oncologys annual meeting in Barcelona, cancer researchers unveiled results from scores of important clinical trials.You can read full stories from us on iTeos Therapeutics much-anticipated TIGIT drug data and Bristol Myers Squibbs 10-year data from Opdivo and Yervoy. Other notable trial readouts weve summarized in brief here:People with cancer can sometimes experience a serious metabolic condition called cachexia, which leads to weight loss and can blunt the effectiveness of treatment. There are currently no treatments. Clinical trial results presented Saturday at ESMO and published in The New England Journal of Medicine, though, suggest Pfizer may have discovered one. The company's drug, ponsegromab, helped people with cancer cachexia regain weight and improved appetite, symptoms and physical activity, the data show. Moreover, Pfizer believes the results confirm that ponsegromab's target, a protein called GDF-15, is an important driver of cachexia. Ned PagliaruloJohnson & Johnsonhas high expectations for TAR-200, a medical device that releases chemotherapy into the bladder. At ESMOon Monday, the company reported Phase 2 results showing the therapy helped shrink or eliminate tumors prior to surgery in people with muscle-invasive bladder cancer. According to the company, 42% of those who received TAR-200 and an experimental J&J immunotherapy called cetrelimabhad no evidence of cancer on a tumor scan, compared to 23% of those who got only cetrelimab. The overall response rate for the combination was 60%, versus 36% for cetrelimab monotherapy. TAR-200 is in late-stage testing for the non-muscle invasive form of the disease as well. Jonathan GardnerESMO follows one week after Summit Therapeutics presented Phase 3 trial data that showed, for the first time, a drug beating Keytruda head-to-head in first-line lung cancer. Not surprisingly, the finding has shone a spotlight on drugs that work like Summit's, which binds to both the PD1 target of Keytruda and another well-known cancer-related protein called VEGF. BioNTech has one and, at ESMO, presented three early datasets. Separately, Instil Bio shared development plans for its similar drug. Daina Graybosch, an analyst at Leerink Partners, wrote in a client that note that she expects “growing awareness of the scope of the opportunity“ will be balanced out by “the realization that the scientific debate is complex, and development path will be long.“ Ned PagliaruloResearchers on Sunday revealed multiple study results illuminating the long-term impact cancer immunotherapies have had on the survival of people with melanoma. One of those studies found that advanced melanoma patients who received Merck & CosKeytrudahad a 29% reduced risk of death compared to those treated with Bristol Myers SquibbsYervoy. People who got Keytruda lived a median of 33 months, compared with 16 months for those on Yervoy. After 10 years of follow-up, 34% of Keytruda recipients were still alive, compared with 24% of people who got Yervoy. Jonathan GardnerRelay Therapeutics has company in its quest to build a better PI3Ka inhibitor, a type of cancer drug that's been limited by its toxicity. On Sunday, privately held Scorpion Therapeutics unveiled initial data for its experimental drug, STX-478, in people with solid tumors and PI3Ka mutations. As a monotherapy, Scorpion's drug led to tumor responses in 23% of breast cancer patients and 21% overall across tumor types. Notably, no patients discontinued the study due to treatment-related side effects, which were mostly mild or moderate in nature. Ned Pagliarulo '