Inclacumab fails to reduce pain crises vs. a placebo in SCD trial
THRIVE-131 study tested antibody therapy's ability to lower VOC rates
Pfizer’s investigational therapy inclacumab failed to outperform a placebo in reducing the rate of vaso-occlusive crises — episodes marked by painful inflammatory responses — in people with sickle cell disease (SCD), according to new data from the Phase 3 THRIVE-131 study.
“We recognize this news is disappointing for the sickle cell community, and we share their disappointment,” Michael Vincent, MD, PhD, chief inflammation & immunology officer at Pfizer, said in a company press release detailing the trial results.
“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,” Vincent said.
In SCD, a faulty version of the oxygen-carrying hemoglobin protein causes red blood cells to take on the sickle-like shape that gives the disease its name. Because these sickled cells are prone to clumping, they can block blood flow and trigger inflammation, leading to painful vaso-occlusive crises, or VOCs.
Inclacumab aimed to prevent blockages leading to VOCs
Inclacumab is an antibody-based therapy designed to prevent the blockages that lead to VOCs by disrupting the interactions between sickled red blood cells, blood vessel walls, platelets — cell fragments involved in blood clotting — and inflammatory immune cells.
THRIVE-131 (NCT04935879) evaluated inclacumab in 241 SCD patients, ages 16 and older, who had experienced two to 10 VOCs within the year before the study. Participants were randomly assigned to receive inclacumab or the placebo, given via an infusion into the bloodstream, once every 12 weeks, for 48 weeks, or nearly a year.
The study’s main goal was to assess the therapy’s ability to reduce the rate of VOCs.
However, Pfizer has now announced that the study did not meet its primary goal, which was a statistically significant difference at 48 weeks in the rate of VOCs in SCD patients treated with inclacumab compared with those given the placebo.
Inclacumab was generally well tolerated, according to the company. The most commonly reported treatment-emergent adverse events in either group were anemia, or low red blood cell counts or hemoglobin levels, joint pain, back pain, headache, malaria, SCD with crisis, and upper respiratory tract infection.
We are deeply grateful to the participants and investigators for their contributions to this important work. … Their efforts are invaluable in informing future sickle cell research.
Participants who completed treatment in THRIVE-131 were eligible to enroll in THRIVE-133 (NCT05348915), an open-label extension study to evaluate the long-term safety of inclacumab. Whether that study is ongoing was not disclosed.
“We are deeply grateful to the participants and investigators for their contributions to this important work,” Vincent said. “Their efforts are invaluable in informing future sickle cell research.”
Pfizer also noted that “analyses of the data will be shared with the scientific and patient community in due course.”
The company added that it is “actively progressing next steps for its broader SCD portfolio,” which includes the experimental therapy osivelotor.
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