Pfizer Faces Major Phase 3 Test After Key Cancer Win

Pfizer has emerged as a frontrunner in addressing cancer cachexia, a debilitating condition characterized by severe weight loss and muscle wasting, which currently has no approved treatments in the United States or Europe. At the European Society for Medical Oncology (ESMO) conference, Pfizer presented data indicating that their GDF-15-directed monoclonal antibody, ponsegromab, showed promise in helping cancer patients gain weight and improve appetite, physical activity, and muscle mass in a Phase 2 trial.

Analysts from Leerink Partners believe ponsegromab has the potential to become a blockbuster drug, possibly achieving sales of over $1 billion. However, before Pfizer can proceed with a registrational study next year, several questions need to be resolved. Cancer cachexia not only affects a patient's ability to tolerate cancer treatments but also increases healthcare resource utilization, leading to significant clinical and economic burdens. A Pfizer-funded study presented at ESMO highlighted these challenges.

Research suggests that up to 30% of cancer deaths may be linked to cachexia. Moreover, it also impacts patients with chronic conditions like heart failure and chronic obstructive pulmonary disease. Despite its prevalence, the condition has not received adequate attention, according to Min Li, a professor at the Stephenson Cancer Center. Li expressed optimism following the ESMO presentation and the simultaneous publication of the Phase 2 data in the New England Journal of Medicine.

Having a major pharmaceutical company like Pfizer involved in late-stage testing is seen as a significant boost for the field. Andy Judge, president of the Cancer Cachexia Society, expressed hope that Pfizer's findings will lead to more successful trials and further progress in this area.

However, the path ahead is complex. The heterogeneity of cachexia, affecting different cancers at varying rates, could pose challenges in late-stage trials. Min Li noted the lack of consensus on the optimal endpoint for evaluating cancer cachexia. Another obstacle is the systemic nature of the condition, involving multiple organs and tissues. Li mentioned that targeting a single pathway has yielded limited success.

Ponsegromab targets growth differentiation factor 15 (GDF-15). Pfizer's researchers believe that neutralizing GDF-15 could improve caloric intake and boost physical activity. The drug, discovered by Pfizer, first entered clinical trials in 2018 with healthy volunteers. It is also being tested in patients with heart failure, specifically those with cardiac cachexia or fatigue, with results expected by next March.

Li also highlighted other potential pathways for targeting cancer cachexia, including myostatin/activin signaling, IL-6, ghrelin, circular RNAs, metabolic enzymes, TNF, and TGF. More studies are needed to prove that stabilizing muscle and fat reserves can directly impact patient outcomes, said Michael Rosenthal from Dana-Farber/Brigham and Women’s Hospital.

Doctors are also looking for improvements in daily activities. Vincent Chung, an oncologist at City of Hope, emphasized the importance of evaluating the drug's impact on ECOG performance status and overall survival in randomized chemotherapy trials.

Pfizer is not new to pioneering treatments in challenging fields. Other companies exploring treatments for cachexia include Actimed Therapeutics, TMS, and Vistagen. However, David Hui from the University of Texas MD Anderson Cancer Center emphasized the importance of a multi-dimensional approach to treating cachexia, involving diet, exercise, and medications for symptom management.

Doctors currently address cachexia with a team-based approach, involving dietitians, physical therapists, and supportive palliative care teams to improve patient outcomes. Hui highlighted the importance of this comprehensive care model in addressing the varied concerns related to cachexia.