ponsegromab (PF-06946860) / Pfizer - LARVOL DELTA

Psychometric Validation and Meaningful Within-Patient Change of the FAACT-5IASS in Patients With Cancer Cachexia (ISPOR 2025) - P2 | "We aimed to further evaluate the psychometric properties of the FAACT-5IASS scale in patients with other tumors and cachexia using data from a recent randomized trial (as reported in Groarke et al, NEJM, 2024). We evaluated the measurement properties of the FAACT-5IASS using data from the ponsegromab randomized, double-blind, placebo-controlled, phase 2 study (ClinicalTrials.gov number=NCT05546476) in adult patients with NSCLC, colorectal, or pancreatic cancer and diagnosis of cachexia based on Fearon criteria... The FAACT-5IASS demonstrated robust psychometric properties and a MWPC of 2.86-3.58, supporting the use of the scale in research focused on evaluating appetite and anorexia symptoms in cancer cachexia patients."

Clinical • Anorexia • Cachexia • Colorectal Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor

Humanized GDF15 model for simulating weight loss induced by GDF15 secretion in tumors (AACR 2025) - "After 7 days of inoculation, the mice were grouped based on body weight and tumor size, and the treatment group received 10 mg/kg of a ponsegromab analog on the same day. We observed significant weight gain in the treated group compared to the control group, indicating that B-hGDF15 mice and B-hGDF15 MC38 provide an excellent preclinical in vivo model for testing GDF15-targeted drugs."

Oncology • GDF15

Preclinical models of cancer cachexia: Bridging the gap to clinical applications (AACR 2025) - "Motor function assessed via rotarod performance, and grip strength showed coordination and strength impairments in tumor-bearing mice, while Ponsegromab significantly improved grip strength and physical performance in comparison to the hIgG1-treated control group.In conclusion, our validated preclinical cachexia models closely align with clinical CC manifestations, providing a robust platform for the evaluation of novel therapeutic strategies. These models enable detailed exploration of CC mechanisms and support the development of effective interventions to mitigate cachexia and improve patient outcomes."

Preclinical • Oncology • GDF15

FL-501 is a potential best in class GDF-15 inhibitor with extended half-life and potent anti-cachexia activity in preclinical models (AACR 2025) - "In this therapeutic model, mice were treated with cisplatin (5 mg/kg) alone or in combination with either FL-501 or ponsegromab...Further, the targeted inhibition of GDF-15 with FL-501 was able to effectively reverse characteristics of cancer cachexia in multiple pre-clinical models. Taken together, these findings support the continued evaluation of FL501 and its progression into the clinic."

Preclinical • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • GDF15

Baseline circulating growth differentiation factor-15 and the cancer phenotype in the PROACC-1 phase 2 study of the efficacy and safety of ponsegromab in patients with cancer cachexia. (ASCO 2025) - P2 | "Clinical Trial Registration Number: NCT05546476 The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Clinical • P2 data • Cachexia • Oncology • GDF15

GARDEN TIMI 74: A Study of Ponsegromab in People With Heart Failure (clinicaltrials.gov) - P2 | N=457 | Terminated | Sponsor: Pfizer | N=781 ➔ 457 | Trial completion date: May 2026 ➔ Mar 2025 | Active, not recruiting ➔ Terminated | Trial primary completion date: May 2026 ➔ Mar 2025; Following a prespecified interim analysis, and in consultation with the independent Data Monitoring Committee, the Sponsor terminated the study

Enrollment change • HEOR • Trial completion date • Trial primary completion date • Trial termination • Cardiovascular • Congestive Heart Failure • Heart Failure • GDF15

Oncology: What You May Have Missed in 2024. (PubMed, Ann Intern Med) - "Targeted therapies and antibody-drug conjugates, including trastuzumab deruxtecan and enfortumab vedotin, are enhancing precision treatment options in metastatic cancer. Meanwhile, advances in supportive care, such as magnetic resonance imaging-guided prostate cancer screening, ponsegromab for cachexia, and celiac plexus radiosurgery for pain, show enhanced symptom management and quality of life for patients. These innovations highlight the critical role of multidisciplinary approaches, where internal medicine physicians contribute to co-management and toxicity monitoring, ultimately optimizing patient care. By staying current with these developments, internal medicine physicians are positioned to navigate complex oncologic care, ensuring that the benefits of novel therapies are maximized while mitigating their challenges."

Journal • Cachexia • Genito-urinary Cancer • Oncology • Pain • Prostate Cancer • Solid Tumor

New trends in supportive care of head and neck cancers. (PubMed, Curr Opin Oncol) - "In recent years, new knowledge has emerged regarding the underlying causes and predictive models for the supportive care of HNC patients. Unfortunately, this expanding body of knowledge primarily adds to complexity without translating into practical applications or substantial improvements for patients. Future efforts should prioritize the standardization of therapeutic algorithms, and the generation of robust evidence based on existing preclinical models."

Journal • Cachexia • Dermatitis • Dermatology • Gastrointestinal Disorder • Head and Neck Cancer • Immunology • Infectious Disease • Mucositis • Oncology • Pain • Solid Tumor

Ponsegromab for the Treatment of Cancer Cachexia. Reply. (PubMed, N Engl J Med) - No abstract available

Journal • Cachexia • Oncology

Ponsegromab for the Treatment of Cancer Cachexia. (PubMed, N Engl J Med) - No abstract available

Journal • Cachexia • Oncology

Ponsegromab for the Treatment of Cancer Cachexia. (PubMed, N Engl J Med) - No abstract available

Journal • Cachexia • Oncology

Growth differentiation factor 15 aggravates sepsis-induced cognitive and memory impairments by promoting microglial inflammatory responses and phagocytosis. (PubMed, J Neuroinflammation) - "The levels of GDF15 were elevated in the brains of septic mice. Targeting GDF15 with an anti-GDF15 antibody was found to improve sepsis-induced cognitive and memory impairment by reducing the microglial inflammatory response and phagocytosis. These results indicate that GDF15 could serve as an important therapeutic target for treating SAE."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Infectious Disease • Inflammation • Septic Shock • GDF15

GARDEN TIMI 74: A Study of Ponsegromab in People With Heart Failure (clinicaltrials.gov) - P2 | N=781 | Active, not recruiting | Sponsor: Pfizer | Recruiting ➔ Active, not recruiting

Enrollment closed • HEOR • Cardiovascular • Congestive Heart Failure • Heart Failure • GDF15

Ponsegromab for Cancer Cachexia - A New Dawn for an Old Condition? (PubMed, N Engl J Med) - No abstract available

Journal • Cachexia • Oncology

Thank you @theNCI Blog for highlighting important strides in #cachexia research including recent @Nejm report investigating the anti-GDF15 drug ponsegromab

Will Ponsegromab Be a Game Changer for Cancer Cachexia? (National Institute of Health) - "The group of participants treated with the highest dose, 400 mg, in fact, gained back more than 5% of their body weight, reported one of the study's investigators, Jeffrey Crawford...In addition, ponsegromab didn't appear to interfere with patients' responses to their cancer treatments, Dr. Crawford explained. But because the trial was small and people were only treated for 12 weeks, 'it's hard to say definitively' whether that's the case, he cautioned."

Media quote

GARDEN TIMI 74: A Study of Ponsegromab in People With Heart Failure (clinicaltrials.gov) - P2 | N=781 | Recruiting | Sponsor: Pfizer | N=416 ➔ 781 | Trial completion date: Jun 2025 ➔ Mar 2026 | Trial primary completion date: Mar 2025 ➔ Mar 2026

Enrollment change • HEOR • Trial completion date • Trial primary completion date • Cardiovascular • Congestive Heart Failure • Heart Failure • GDF15

New cancer cachexia treatment boosts weight gain and patient activity - "Side effects were minimal, Dunne said, and in fact ponsegromab appeared to be safer than common appetite stimulants used by cachexia patients....'This is super exciting,' said Dunne."

Media quote

#ESMO24 Possible breakthrough in cancer #cachexia with #Ponsegromab, anti-GDF 15. Significant weight gain, especially in patients with #colorectalcancer. @CathyEngMD @CCAlliance @FightCRC @OncoAlert

Novel Agent Effective for Cancer Wasting Disorder (MedPageToday) - "'This study supports GDF-15 as a primary driver of cachexia and an important therapeutic target in this area of unmet medical need for our patients,' Crawford concluded....During a discussion period, Crawford was asked whether ponsegromab would advance to phase III study and evaluate survival outcomes."

Media quote

Ponsegromab for the Treatment of Cancer Cachexia. (PubMed, N Engl J Med) - P2 | "Among patients with cancer cachexia and elevated GDF-15 levels, the inhibition of GDF-15 with ponsegromab resulted in increased weight gain and overall activity level and reduced cachexia symptoms, findings that confirmed the role of GDF-15 as a driver of cachexia. (Funded by Pfizer; ClinicalTrials.gov number, NCT05546476.)."

Clinical • Journal • Cachexia • Colorectal Cancer • Gastrointestinal Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • GDF15

NEJM at ESMO - Ponsegromab in Cancer Cachexia. (PubMed, N Engl J Med) - No abstract available

Journal • Cachexia • Oncology

Efficacy and safety of ponsegromab, a first-in-class, monoclonal antibody inhibitor of growth differentiation factor 15, in patients with cancer cachexia: A randomized, placebo-controlled, phase II study (ESMO 2024) - P2 | "Ponsegromab improved weight, symptoms, overall activity, and skeletal muscle mass in patients with cancer cachexia and elevated GDF-15, confirming GDF-15 as a primary driver of cancer cachexia."

Clinical • Late-breaking abstract • P2 data • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • GDF15

Hot off the press @NEJM In a randomized Ph II Ponsegromab, an anti-GDF15 mAB, increased weight gain, overall physical activity and reduced cachexia symptoms in patients with #cachexia and GDF-15 https://nejm.org/doi/full/10.1056/NEJMoa2409515

Clinical

Pfizer Presents Positive Data from Phase 2 Study of Ponsegromab in Patients with Cancer Cachexia (Businesswire) - P2 | N=187 | PROACC-1 (NCT05546476) | Sponsor: Pfizer | "Pfizer Inc...announced its Phase 2 study of ponsegromab...met its primary endpoint of change from baseline in body weight compared to placebo in people with cancer cachexia and elevated levels of GDF-15...Results will be presented today as a late-breaking Proffered Paper Presentation (LBA82) at the European Society for Medical Oncology (ESMO) 2024 Congress and have simultaneously been published in The New England Journal of Medicine...The Phase 2 study included 187 participants with non-small cell lung cancer, pancreatic cancer, or colorectal cancer. Ponsegromab demonstrated significant and robust increases in body weight after 12 weeks across all doses: 2.02% (95% confidence interval (CI), -0.97 to 5.01%) in the 100 mg treatment group....Based on these positive results, Pfizer is discussing late-stage development plans with regulators with the goal of starting registration-enabling studies in 2025."

New trial • P2 data • Cachexia • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Pancreatic Cancer • Solid Tumor