Agios' next-up PK activator quelled transfusion need in select patients, teeing up placebo test

Agios Pharmaceuticals' second-in-command PK activator has passed a mid-stage checkpoint, lessening the need for transfusions in select anemia patients and teeing up the second part of a phase 2 study for the middle of next year.

The rare disease company reported Monday that “proof-of-concept has been achieved” in a phase 2a study of AG-946, a pyruvate kinase (PK) activator for anemia in patients with lower-risk myelodysplastic syndromes. The goal centered on success in patients with low transfusion burden, with Agios reporting that four out of 10 patients in that subgroup achieved a “transfusion independence endpoint.” One patient out of the 22 that were enrolled actually hit the hemoglobin response endpoint within the 16-week treatment period. 

The trial recruited 22 patients who were classified as either non-transfused or low transfusion burden. The former meant patients had received less than three red blood cell units in the 16 weeks before being dosed while the latter meant receiving three to seven red blood cell units in the same period or less than four units in the eight weeks before being dosed.

The transfusion independence endpoint, which applied only to patients defined as having a low transfusion burden, was defined as being transfusion-free for at least eight consecutive weeks during the 16-week treatment period. It’s unclear if any of the four patients needed transfusions outside of the 16-week core period, and if so, when. More data are set to be presented at a medical conference next year. 

Agios Chief Medical Officer and R&D chief Sarah Gheuens, M.D., Ph.D., said in a release that the company was “pleased with the results.” 

“A meaningful reduction in transfusions allows patients to potentially decrease visits to the clinic and experience improved quality of life,” she said. The looming placebo portion will be where Agios really tests the med’s mettle, which is expected in the middle of 2024. 

Agios is about a year and a half removed from an R&D recalibration that set the PK-focused course it's now on. The biotech recently bolstered that ambition by scooping up Alnylam’s preclinical siRNA blood disease program for $17.5 million upfront., with IND-enabling studies slated before the end of the year. 

Both the preclinical program and AG-946 are running behind FDA-approved PK deficiency treatment Pyrukynd, which was approved in February 2022. The therapy brought in $19.7 million in revenue through the third quarter of this year, according to tallies from the company’s 2023 earnings reports to date.