Pfizer suffers another hit to its GBT sickle cell portfolio

Pfizer's $5.4 billion takeover of Global Blood Therapeutics three years ago is starting to look like a poor deal.

Less than a year after it was forced to withdraw GBT's sickle cell disease (SCD) therapy Oxbryta from all world markets after finding an "imbalance" in deaths in its clinical trials programme, Pfizer has now reported a failed phase 3 trial for another SCD candidate from the acquisition.

The phase 3 THRIVE-131 study of P-selectin inhibitor inclacumab was unable to meet its objective of achieving a significant reduction in vaso-occlusive crises (VOCs) – the excruciatingly painful attacks that intermittently affect patients with SCD – compared to placebo.

The study was carried out in SCD patients aged 16 and over and tested an intravenous dose of inclacumab given every 12 weeks over 48 weeks.

On the plus side, the antibody was fairly well tolerated, but Pfizer's chief inflammation and immunology officer, Michael Vincent, acknowledged that the efficacy result "is disappointing for the sickle cell community."

In SCD, P-selectin is believed to drive the binding of sickled red blood cells and platelets to blood vessels, leading to inflammation and VOCs. Some years ago, Pfizer was also working with GlycoMimetics on an antagonist of E-, P- and L-selectins, rivipansel, as an SCD treatment that also failed in phase 3 and was abandoned in 2019.

Meanwhile, another P-selectin inhibitor, Novartis' Adakveo (crizanlizumab), reached the market as a treatment to reduce VOCs in SCD but was withdrawn from sale in Europe after it failed a confirmatory phase 3 trial and – while it remains on sale in the US – has seen modest sales well short of its once-touted blockbuster status.

"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," said Vincent.

If that does spell the end for inclacumab, as seems likely, Pfizer will be left with one asset from the GBT acquisition – haemoglobin S polymerisation inhibitor osivelotor – and an ongoing effort to rehabilitate Oxbryta. At one point, Pfizer was modelling peak sales of $3 billion a year from the three drugs.

Osivelotor is in a phase 3 trial as a chronic treatment for SCD, but Pfizer has now revealed that patient enrolment is currently paused due to a partial clinical hold issued by the FDA at the end of last year. Meanwhile, it has said updates from a phase 2/3 trial of the drug will be shared "as available."