Schrodinger Halts Development of Blood Cancer Drug After Patient Deaths

Schrodinger, a New York-based biotech company, has announced the discontinuation of its investigational CDC7 blocker, SGR-2921, following two patient deaths in a Phase I clinical trial. The drug, which was being tested for relapsed/refractory acute myeloid leukemia and high-risk myelodysplastic syndromes, showed early evidence of monotherapy activity but was ultimately deemed to have an unfavorable risk/benefit profile.

Patient Deaths and Clinical Trial Results

The Phase I dose-escalation study of SGR-2921 revealed promising initial results, with the company reporting "early evidence of monotherapy activity." However, the drug was "considered to have contributed" to two patient deaths, leading Schrodinger to conclude that further development, including as part of a combination regimen, would be "difficult to pursue."

Margaret Dugan, Chief Medical Officer at Schrodinger, stated that while the decision to discontinue SGR-2921 is "disappointing," it is "the right decision for patients." The announcement had an immediate impact on Schrodinger's stock, which dropped 17.5% before the opening bell on Thursday.

Schrodinger's Oncology Pipeline

Despite the setback with SGR-2921, Schrodinger maintains a robust oncology portfolio:

• SGR-1505: A small molecule drug for relapsed/refractory B cell malignancies, which demonstrated clinical activity in various histologies, including chronic lymphocytic leukemia and Waldenstrom macroglobulinemia in initial Phase I data released in June.

• SGR-3515: Another small molecule in development for solid tumors. Preclinical data from October 2024 indicated stronger and more durable anti-tumor activity compared to previous inhibitors. A Phase I study for this asset is currently recruiting, with a primary completion date set for October 2026.

Industry-wide Patient Safety Concerns

The pharmaceutical industry has recently faced several challenges related to patient safety in clinical trials:

• Sarepta Therapeutics reported three mortalities associated with its gene therapy portfolio, including two with the Duchenne muscular dystrophy treatment Elevidys and one with an investigational product for limb-girdle muscular dystrophy.

• CytomX, a California-based company, reported one patient death linked to its antibody-drug conjugate CX-2051 in a colorectal cancer trial. Despite this, a safety committee has supported the continuation of the Phase I study.

• Allogene reported a mortality in the Phase II study of its lymphoma CAR T cell therapy cemacabtagene ansegedleucel, attributed to ALLO-647, an antibody used to suppress the immune system before cell therapy infusion.

• Agios Pharmaceuticals reported three patient deaths associated with its anemia therapy Pyrukynd, though the company maintained that these events have "not altered the established benefit-risk profile" of the drug.

These incidents underscore the critical importance of patient safety in drug development and the challenges faced by pharmaceutical companies in balancing potential benefits with risks in clinical trials.