Pfizer is mulling its options after its investigational sickle cell disease drug failed to meet the primary endpoint in a Phase III trial.

The THRIVE-131 study (NCT04935879) was evaluating inclacumab, an investigational P-selectin inhibitor, in patients 16 years of age and older with sickle cell disease.

The trial failed to meet its primary endpoint of a significant reduction in the rate of vaso-occlusive crises (VOCs) after 48 weeks, placing the drug’s future in jeopardy.  

Pfizer's chief inflammation and immunology officer Dr Michael Vincent, said: “While the THRIVE-131 results did not meet our expectations, we remain committed to better understanding these results and sharing them with the medical and sickle cell community in the interest of advancing our collective understanding of sickle cell disease. We remain focused on our mission of bringing much-needed treatments to patients with sickle cell disease.”

The therapy was generally well tolerated in THRIVE-131, with the most common adverse events (AEs) being anaemia, arthralgia, back pain, headache, malaria, sickle cell anaemia with crisis, and upper respiratory tract infection.

Analyses of the data will be shared with the scientific and patient community in due course.

The therapy is still being assessed in the THRIVE-133 OLE trial (NCT05348915) to evaluate the long-term safety of inclacumab.

If approved, GlobalData predicts global sales of the drug to reach $267m in 2031.

GlobalData is the parent company of Clinical Trials Arena.

Pfizer’s sickle cell disease woes

This is the latest hit in sickle cell disease for Pfizer. In September 2024, it withdrew its therapy Oxbryta (voxelotor) in all approved markets after data suggested an imbalance in VOCs and fatal events.

The company has reviewed and shared the data with the US Food and Drug Administration (FDA) and European Medicines Agency (EMA).

The company is also awaiting the lifting of a partial clinical hold by the FDA on its Phase III trial of osivelotor, a haemoglobin S polymerisation inhibitor, in sickle cell disease. The FDA’s order has paused enrolment into the trial, with Pfizer stating data will be shared as it becomes available.

Approved therapies in the sickle disease treatment space are combating slow growth. Vertex and CRISPR Therapeutics’ Casgevy (exagamglogene autotemcel) only reached revenue of $10m in 2024, with a $2.2m price tag per patient proving a barrier to initial uptake. Vertex said it expects the number of new patients initiating cell collection to grow significantly throughout 2025, with signals that this is already happening. GlobalData predicts Casgevy sales will increase significantly in 2025, with a forecast of $107m, with projections that the gene therapy will reach blockbuster status in 2030.

The therapy gained approval by the National Institute for Health and Care Excellence (NICE) for use in sickle cell disease in January 2025, meaning it is now available for use on the UK’s National Health Service (NHS).