With a range of crucial updates across disease spaces, including sickle cell disease (SCD), thalassemia, and other bleeding disorders, our June 2024 month-in-review for hematology focused on the latest updates to the hematologic pipeline.

Pipeline News

MITIGATE: Inebilizumab Reduces Risk of IgG4-Related Disease Flare

Topline results from the Phase 3 MITIGATE study showed inebilizumab-cdon (UPLIZNA®) achieved an approximately 90% reduction in the risk of immunoglobulin G4-related disease (IgG4-RD) flare, compared with placebo, and improved annualized flare rates.

“These data mark a major milestone for the IgG4-RD community and provide substantial insight into not only how inebilizumab can help manage IgG4-RD, but also key insights into the nature of this condition,” said principal investigator John Stone, MD, Harvard Medical School and Massachusetts General Hospital.

RUBY: Reni-Cel Displays Promising Efficacy, Safety for Sickle Cell Disease

Results from the Phase 1/2/3 RUBY trial showed patients with SCD treated with renizgamglogene autogedtemcel (reni-cel), formerly known as EDIT-301, remained free of vaso-occlusive events (VOEs) in the post-infusion period.

“I am encouraged by these results from the RUBY trial, demonstrating this investigational gene editing medicine has been well-tolerated and shows promising efficacy for people living with SCD,” said Rabby Hanna, MD, Cleveland Clinic Children’s.

Reni-Cel Displays Clinical Benefit for Transfusion-dependent Beta Thalassemia

Data from the Phase 1/2 EdiTHAL trial shows that reni-cell remained well-tolerated and displayed promising efficacy for patients with transfusion-dependent beta-thalassemia (TDT).

“The preliminary safety and efficacy results from the EdiThAL trial demonstrate this investigational medicine has been well-tolerated and shows promising efficacy for patients,” said Haydar Frangoul, MD, MS, Sarah Cannon Research Institute.

Exa-Cel Shows Long-Term Clinical Benefit in Sickle Cell Disease, TDT

Long-term efficacy results confirmed the durable benefit of exagamglogene autotemcel (exa-cel; CASGEVY™) in the treatment of severe SCD or TDT. Data from ≥100 patients treated with exa-cel remained consistent with primary and secondary endpoint analyses from the CLIMB clinical trials, with the longest follow-up extending more than 5 years.

“The transformative benefit seen in patients with SCD in the trial is impressive given the significant and cumulative burden of disease faced by people living with this blood disorder,” Frangoul said.

Mitapivat Achieves Phase 3 Endpoint in Non-Transfusion-Dependent Thalassemia

Positive data from the Phase 3 ENERGIZE study showed the efficacy of oral mitapivat (PYRUKYND) for adults with non-transfusion-dependent alpha- or beta-thalassemia. In ENERGIZE, mitapivat achieved a statistically significant increase in hemoglobin response rate versus placebo.

“Based on the data collected in the ENERGIZE study, mitapivat has the potential to become a foundational treatment for non-transfusion-dependent thalassemia,” said Ali Taher, MD, PhD, American University of Beirut Medical Center.

KP104 Achieves Robust Efficacy in Paroxysmal Nocturnal Hemoglobinuria

Long-term Phase 2 results demonstrate the potential of KP104 as an optimal first-line monotherapy to safely and effectively control intravascular and extravascular hemolysis of paroxysmal nocturnal hemoglobinuria (PNH).

“We are very encouraged by the robust efficacy and favorable safety profile demonstrated by KP104 in our Phase 2 study. These long-term results support the advancement of KP104 into Phase 3 trials,” said Wenru Song, Kira Pharmaceuticals.

Phase 2 AURORA Trial Demonstrates Clinical Activity of Bitopertin for EPP

Analyses from the Phase 2 AURORA study demonstrated the potential clinical benefit of bitopertin, an orally administered inhibitor of glycine transporter 1 (GlyT1), for the treatment of erythropoietic protoporphyria (EPP).

According to the data, bitopertin achieved significant reductions in protoporphyrin IX (PPIX), and meaningful improvement in light tolerance, phototoxic reactions, and quality of life, in patients with EPP.

ELA026 Shows Promise for Secondary HLH in Phase 1b Study

ELA026 had a high overall response rate and favorable safety across a range of patients with secondary hemophagocytic lymphohistiocytosis (sHLH) in Phase 1b. In particular, treatment-naive patients with malignancy-associated HLH experienced a 100% overall response rate at week 4 and improved survival at 2 months.

“The data show very promising results for ELA026 as a potential treatment for sHLH, which is a challenging disease that is devastating for patients and has no approved treatment options,” said Swaminathan P. Iyer, MD, The University of Texas MD Anderson Cancer Center.

Mezagitamab Achieves Platelet Response, Favorable Safety in ITP Treatment

Mezagitamab (TAK-079) achieved positive results in patients with persistent or chronic primary immune thrombocytopenia (ITP) in the Phase 2b, randomized TAK-079-1004 study. These results included rapid and sustained increases in platelet counts across three dose levels and a favorable safety profile.

“These Phase 2b trial results are especially encouraging because they show mezagitamab’s favorable efficacy and safety profile–setting the stage for the generation of additional clinical evidence for this anti-CD38 monoclonal antibody with best-in-class potential for efficacy in ITP,” said David Kuter, MD, DPhil, Harvard Medical School and Massachusetts General Hospital.

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