Amgen and Ideaya Discontinue Cancer Combination Trial, Shift Focus to Individual PRMT5 Inhibitor Programs

Amgen and Ideaya Biosciences have mutually agreed to terminate their cancer combination study, marking a significant shift in their collaborative efforts to enhance the efficacy of PRMT5 inhibitors in solid tumors. The decision, announced in Ideaya's fourth-quarter business report, comes as both companies pivot to focus on their individual PRMT5 inhibitor programs.

Combination Trial Termination and Strategic Realignment

The now-discontinued trial was evaluating the combination of Amgen's PRMT5 inhibitor AMG 193 with Ideaya's MAT2A inhibitor IDE397. This partnership, established in July 2022, aimed to target solid tumors null for the MTAP marker. Despite the initial promise, both companies have decided to wind down the current study and abandon plans for dose expansion.

Ideaya is now redirecting its efforts towards studying IDE397 in combination with its own PRMT5 inhibitor, IDE892, in non-small cell lung cancer (NSCLC). This strategic pivot was unveiled at Ideaya's R&D event in December, where CEO Yujiro Hata touted IDE892 as a potential best-in-class PRMT5 inhibitor specifically designed to complement IDE397.

Amgen's Ongoing PRMT5 Inhibitor Development

Despite the setback in the combination trial, Amgen continues to advance AMG 193 as a monotherapy. The company has initiated a Phase II study of AMG 193 in MTAP-null patients with advanced NSCLC, with enrollment currently ongoing. Additionally, Amgen is conducting a Phase I/Ib/II study of AMG 193 in MTAP-null solid tumors and two Phase Ib studies evaluating the asset alone or in combination for various cancer types, including thoracic malignancies and gastrointestinal cancers.

Last year, Amgen shared first-in-human data for AMG 193 monotherapy, demonstrating a 21.4% objective response rate in evaluable patients across eight different tumor types. The study also revealed adverse events in approximately half of the patients, with nausea, fatigue, and vomiting being the most common side effects.

Competitive Landscape and Future Outlook

The termination of the Amgen-Ideaya combination trial reshapes the competitive landscape in the PRMT5 inhibitor space. Several pharmaceutical companies, including AstraZeneca, BeiGene, Bristol Myers Squibb, Servier, and Tango Therapeutics, are actively developing PRMT5 inhibitors. BeiGene, Servier, and Ideaya are now at the forefront of companies pursuing both PRMT5 and MAT2A inhibitors.

As the field evolves, the focus shifts to individual company efforts to optimize their PRMT5 inhibitor programs. The coming months will likely see increased attention on clinical trial results and potential new combination strategies as companies strive to improve efficacy in treating MTAP-null solid tumors.