Pfizer has terminated a Phase I clinical trial evaluating PF-07258669, an experimental drug targeting unintended weight loss in older adults, according to a recent update to the ClinicalTrials.gov registry. The PF-07258669 clinical trial (NCT07086664), initially designed to investigate safety and pharmacodynamic effects in participants aged 60 to 89 years, was discontinued after enrolling only seven participants, with the source indicating that the study was “prematurely discontinued due to a business decision”, with no safety concerns related to the molecule.

The terminated trial was structured as a randomized, double-blind, placebo-controlled interventional study. Researchers planned to examine the safety, tolerability, and pharmacodynamic impact of PF-07258669 in older participants, with a specific focus on individuals at risk of malnutrition. The protocol included a comprehensive 26-week research timeline, incorporating nine in-person visits and four telehealth consultations. PF-07258669 entered Phase I study in 2021 and completed three other early studies before the recent termination.

Industry context

Pfizer’s PF-07258669 is a selective, orally bioavailable small‑molecule antagonist/inverse agonist of the melanocortin‑4 receptor (MC4R). MC4R is a centrally expressed G protein–coupled receptor (GPCR) with a pivotal role in energy homeostasis, appetite, and food intake. While MC4R agonist Imcivree (setmelanotide; Rhythm Pharmaceuticals) has gained approval for severe obesity conditions, as an antagonist, PF-07258669 was under development for conditions characterized by clinically significant appetite loss and weight loss such as anorexia/cachexia. The molecule emerged from Pfizer’s 2015 partnership with Sosei Heptares (now Nxera Pharma) for the discovery of GPCR-targeted candidates.

Companies set to benefit from Pfizer’s withdrawal include Endevica Bio, whose mifomelatide (formerly TCMCB07) is currently in Phase II study for cancer-related anorexia and cachexia.