Pfizer's Sickle Cell Therapy Setback: Inclacumab Fails in Phase III Trial

Pfizer's ambitious foray into sickle cell disease (SCD) treatment has hit another significant roadblock. The pharmaceutical giant announced that its investigational P-selectin blocker, inclacumab, failed to meet its primary endpoint in the Phase III THRIVE-131 trial for patients with SCD.

Trial Failure and Its Implications

The 48-week THRIVE-131 study, involving over 240 patients, was designed to evaluate inclacumab's efficacy in reducing vaso-occlusive crises (VOCs) in SCD patients. These painful episodes, characteristic of the disease, occur when sickled red blood cells obstruct blood flow. Despite high hopes, Pfizer reported that inclacumab did not significantly lower the rate of VOCs compared to placebo over the treatment period.

This setback adds to a series of disappointments stemming from Pfizer's $5.4 billion acquisition of Global Blood Therapeutics (GBT) in 2022. Inclacumab, obtained through this deal, was positioned as a promising candidate in Pfizer's SCD portfolio. The company's statement acknowledged that the "THRIVE-131 results did not meet our expectations," though specific data were not disclosed.

Broader Implications for Pfizer's SCD Strategy

The failure of inclacumab in Phase III trials follows a string of setbacks in Pfizer's sickle cell disease program:

1. In March 2024, Pfizer discontinued another Phase III trial for inclacumab due to slow enrollment, having recruited only 78 of the targeted 280 patients since December 2021.

2. More critically, in September 2024, Pfizer withdrew Oxbryta, the centerpiece of the GBT acquisition, from the market. This decision came after detecting an elevated risk of deaths and complications in treated patients. Oxbryta had been projected to achieve peak global sales of $3 billion.

These developments have not only impacted Pfizer's SCD pipeline but have also drawn scrutiny from investors. Activist investor Starboard Value, which acquired a $1 billion stake in Pfizer in October 2024, has openly criticized the company's acquisition strategy, labeling the GBT purchase as a "failed" deal that "raised serious questions about its [business development] capabilities."

As Pfizer continues to analyze the THRIVE-131 results, the pharmaceutical industry watches closely to see how this latest setback will influence the company's future direction in sickle cell disease treatment and its broader strategic decisions in the challenging landscape of rare disease therapeutics.