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Pfizer confirmed Wednesday that the termination of a Phase III study in the THRIVE programme for inclacumab will not affect its filing plans for the anti-P-selectin inhibitor in sickle cell disease. A spokesperson told FirstWord that a marketing submission to the FDA remains on track for 2026.A recent update on ClinicalTrials.gov indicated that Pfizer had ended the trial “due to poor accrual and associated recruitment challenges.” The entry noted that 72 patients with sickle cell disease and recurrent vaso-occlusive crises had been enrolled into the study, out of a target of approximately 280. The spokesperson said the trial was halted “due to slow recruitment,” although it has no read across to another late-stage study in the THRIVE programme. That trial is scheduled to read-out in August. Pfizer gained inclacumab through its purchase of Global Blood Therapeutics in 2022. The acquisition also included the HbS polymerisation inhibitor GBT601, now known as PF-07940367. That drug is being investigated in a Phase II/III study for sickle cell disease, with the spokesperson noting that termination of the inclacumab trial does not impact the former programme.

Pictured: Exterior view of Pfizer's office in Belgium/iStock, Alexandros Michailidis Pfizer has discontinued one of its two Phase III studies evaluating the anti-P-selecting antibody inclacumab in sickle cell disease, according to an update on the ClinicalTrials.gov webpage. According to the online database, Pfizer terminated the late-stage study “due to poor accrual and associated recruitment challenges.” The trial was launched in December 2021. However, at the time of Monday’s update, the study had only enrolled 78 patients out of its target size of 280 participants. A Pfizer spokesperson confirmed to Fierce Biotech that the company ended the study “due to slow recruitment,” while adding that the pharma is still eyeing an approval for inclacumab in sickle cell disease by 2026. Originally developed by Global Blood Therapeutics (GBT), Inclacumab is a fully human monoclonal antibody that works by selectively blocking the P-selectin protein, which is known to play a role in cell adhesion and is a clinically validated target for reducing pain associated with vaso-occlusive crises (VOC) in patients with sickle cell disease (SCD). Inclacumab in June 2022 secured the FDA’s Orphan Drug and Rare Pediatric Disease designations for SCD treatment due to its best-in-class potential as well as its quarterly dosing regimen instead of monthly infusions. In August 2022, Pfizer moved to acquire GBT in a $5.4 billion deal for the biotech’s portfolio of SCD therapies, including the FDA-approved Oxbryta (voxelotor), an oral hemoglobin S polymerization inhibitor indicated for patients four years of age and older. Inclacumab was also part of the acquisition. Following the buyout, Pfizer took over the Phase III THRIVE program, which comprised two studies—including the subsequently terminated trial—designed to evaluate the efficacy and safety of inclacumab at reducing VOCs in SCD patients. The other trial remains active and has completed recruitment at 240 patients. According to its ClinicalTrials.gov page, a readout is expected later this year. The termination of Pfizer’s late-stage study follows back-to-back landmark approvals in the SCD space. In December 2023, the FDA on the same day gave its nod to CRISPR Therapeutics and Vertex Pharmaceuticals’ CRISPR-based Casgevy (exagamglogene autotemcel) and bluebird bio’s lentiviral delivery-based Lyfgenia (lovotibeglogene autotemcel). Casgevy and Lyfgenia are cell-based gene therapies. Both products are made from the patients’ own blood stem cells, which are modified, and are given back as a one-time, single-dose infusion. Casgevy has a U.S. list price of $2.2 million per patient, while bluebird set the wholesale acquisition cost of Lyfgenia in the U.S. at $3.1 million. In January 2024, the Centers for Medicare and Medicaid Services announced that it would seek outcomes-based agreements with the developers of these SCD gene therapies to help curb healthcare costs. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

Pictured: Novartis sign at its office in Germany/iStock, TBE The European Commission has formally revoked its conditional marketing authorization for Novartis’ sickle cell disease therapy Adakveo (crizanlizumab), the Swiss pharma company announced Friday. The decision comes after the Committee on Medicinal Products for Human Use (CHMP) recommended in May 2023 to pull the approval following a review of additional Phase III data. The EC’s decision is legally binding, forcing Novartis to withdraw Adakveo from all 27 territories covered by the Commission, including Germany, Sweden and Spain, as well as Iceland, Norway and Liechtenstein, which are part of the European Economic Area. Patients in these territories should discuss alternative treatment options with their doctors and healthcare providers, Novartis said in its announcement. Adakveo is a humanized IgG2 monoclonal antibody that works by binding to the cell adhesion molecule P-selectin, which is found on the surface of platelets and blood vessel endothelium, while disrupting its interaction with its corresponding ligands. In turn, this mechanism of action allows Adakveo to prevent vaso-occlusion in sickle cell disease (SCD). The FDA approved Adakveo in November 2019 as a treatment to lower the frequency of vaso-occlusive crises in SCD patients aged 16 years and above. Nearly a year later, in October 2020, the European Medicines Agency signed off on a conditional approval for the SCD therapeutic and its conversion to standard authorization was contingent on further evidence to validate the efficacy and safety of the product. Novartis ran the Phase III STAND trial to support Adakveo’s full approval in the EU, but in January of this year the company reported that the late-stage study was unable to replicate previous efficacy findings. A preliminary analysis of STAND showed that Adakveo was unable to significantly distinguish itself from placebo in terms of lowering the annualized rates of vaso-occlusive events in SCD patients. The CHMP flagged this and launched its own review of Adakveo, confirming in May 2023 that Novartis’ treatment “did not reduce the number of painful crises leading to a healthcare visit” as compared with placebo. The European regulator also looked at past studies of Adakveo, a managed access program and real-world performance data, noting that these studies “had several limitations, such as the lack of a comparator, and could not be used to show the effect of Adakveo or counterbalance the negative results of the STAND study.” Despite the lack of significant evidence of therapeutic benefit, Novartis pointed out that STAND did not document new safety concerns with Adakveo, and its adverse event pro consistent with what had been established in prior trials. Still, the CHMP noted that STAND “showed a higher rate of severe and serious treatment-related side effects,” therefore concluding that Adakveo’s benefits do not outweigh its risks. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.