Syros links SY-1425 combo to 50%-plus AML complete response rate

Syros Pharmaceuticals' leadership team
Syros Pharmaceuticals' leadership team. (Syros Pharmaceuticals)

Syros Pharmaceuticals has posted updated clinical data on SY-1425 in acute myeloid leukemia (AML). Seven of the 13 newly diagnosed AML patients with a certain biomarker had full complete responses after receiving the RARα agonist in combination with Celgene’s Vidaza. 

SY-1425 flunked a monotherapy assessment in 2017, recording a single-digit complete response rate in AML. Syros stuck with the asset, though, pairing it with Vidaza and Johnson & Johnson’s Darzalex in the belief it can benefit a subset of AML patients who are positive for the RARA biomarker. That belief rests on evidence that RARα, which RARA encodes, is dysregulated in some AML patients. 

Syros presented early data on SY-1425 in combination with Vidaza late last year, revealing that the combination achieved a 50% complete response (CR) rate in biomarker positive patients. One of the four patients recorded as a complete response had incomplete blood count recovery (CRi) rate.

The latest figures shared by Syros improve on that early snapshot. When the one CRi is included in the analysis, the complete response rate now stands at 62%. Three patients have had molecular CRs, up from one in the early analysis, and three have had cytogenetic CRs, indicating the absence of cells with the Philadelphia chromosome in a patient’s bone marrow.

Syros expressed satisfaction with the data.

“These data mark an important milestone in the development of SY-1425,” Syros CMO David Roth, M.D., said in a statement. “SY-1425 in combination with azacitidine continues to demonstrate high complete response rates, rapid onset of action and a favorable tolerability profile in RARA-positive AML patients.”

The complete response rate is notably higher than that associated with Vidaza in the wider AML patient population, which is closer to the 27% Syros saw in the 22 RARA-negative patients enrolled in the combination trial. The median time to CR in RARA-negative patients was 60 days, as compared to 34 days in subjects with the biomarker.

Syros thinks around 30% of newly diagnosed AML patients are RARA-positive. That gives it a sizable population to go after, particularly as its development program is targeting both newly diagnosed and relapsed or refractory AML patients.

However, Syros is some way from showing SY-1425 works as well as it hopes. The data on duration of response in newly diagnosed patients remain immature, although researchers noted RARA-positive status is associated with numerically longer CRs and time on treatment. 

Shares in Syros closed down 4% following the release of the data.