The dream of using anti-CD47 drugs to boost chemotherapy in blood cancer patients is unraveling fast. Weeks after Gilead Sciences stopped its phase 3 trial for futility, ALX Oncology has called a halt to a pair of studies for a rival therapy.
California-based ALX began trialing evorpacept in combination with Bristol Myers Squibb’s Vidaza (azacitidine) and AbbVie and Genentech’s Venclexta (venetoclax) after seeing signs its CD47-blocking fusion protein maximizes the anti-leukemic activity of the approved blood cancer drugs. The combination was more effective than either agent alone in preclinical studies, and passed initial clinical tests in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML).
However, the generation of more clinical data has led ALX to reconsider its plans. In patients with higher risk MDS, adding evorpacept to azacitidine failed to have the desired effect. The activity seen in the 45 recipients of the cocktail “did not substantially improve upon the historical activity of azacitidine alone.”
That finding led ALX to stop the MDS program and assess its work on AML. Because of the connection between the mechanisms of action in MDS and AML, the biotech has decided to end the leukemia trial, too. ALX has torn up plans to start a phase 1b dose optimization clinical evaluation of evorpacept in combination with azacitidine and venetoclax.
Going forward, the biotech will solely focus on combinations with anti-cancer antibodies, antibody-drug conjugates and PD-1/L1 immune checkpoint inhibitors. Cash that was earmarked for the azacitidine and venetoclax trials will go toward existing anti-cancer antibody and checkpoint inhibitor studies.
Evorpacept is being evaluated in a phase 2 trial of patients with HER-2-positive over-expressing metastatic gastric or gastroesophageal junction adenocarcinomas who have already received Genentech’s blockbuster cancer drug Herceptin, Eli Lilly’s Cyramza and chemotherapy. A readout is expected in the second half of this year.
The biotech has also launched a phase 2 trial of evorpacept in combination with chemotherapy and Merck & Co.’s cancer blockbuster Keytruda in patients with recurrent platinum-resistant ovarian cancer. Meanwhile, Sanofi tapped ALX back in April to test evorpacept in combination with the French pharma’s monoclonal antibody Sarclisa in patients with elapsed or refractory multiple myeloma.
ALX ended June with $224.5 million in cash and equivalents, which—along with the option to draw on an additional $40 million loan—it expects to be enough to keep the lights on until mid-2025. That time span covers the completion of the Keytruda combination clinical trials. ALX should also file an IND for ALTA-002 over that period, although issues tied to chemistry, manufacturing and controls have pushed the targeted submission date back to the first quarter of next year.
Gilead and ALX join a growing list of companies who have struggled in the CD47 space. In August last year, AbbVie pulled out of a partnership with I-Mab to assess its candidate lemzoparlimab. That same month, Zai Lab cited “the competitive landscape” as the reason for deprioritizing internal development of ZL-1201.