Zinpentraxin alfa

Roche used an update to reveal the disappearance of a geographic atrophy program from its pipeline. Roche no longer sees the magic in MAGE-A4. The Swiss drugmaker signaled a retreat from the TCR T-cell target in its first quarter results by putting a pair of phase 1 solid tumor programs out to pasture along with hopes of recouping the $490 million paid out for the assets. Genentech, a subsidiary of Roche, put down $100 million in upfront and near-term milestone payments to co-develop one of the candidates with Immunocore in 2018. The drug candidate, a bispecific T-cell engager targeting MAGE-A4, entered the clinic the following year, but both developers have walked away from the program since the release of phase 1 ovarian cancer data late last year. In February, Immunocore stopped funding the program, apart from the cost of winding down the phase 1 trial. The action left Roche’s Genentech with an exclusive worldwide license to the MAGE-A4 HLA-A02 soluble TCR bispecific therapeutic candidate compounds. It seems Roche doesn’t want the compounds, either. The Swiss drugmaker disclosed the axing of RG6290, a drug candidate based on Immunocore’s ImmTAC technology that is also known as IMC-C103C, alongside news of the removal of another MAGE-A4 asset from its pipeline. Roche took the other candidate, HLA-A2-MAGE-A4xCD3 bispecific antibody RG6129, into the clinic months after Immunocore began a phase 1 trial of IMC-C103C. Early this year, Roche said it had stopped enrolling patients in the study of RG6129, pulling the targeted completion date of the trial forward by more than two years in the process. The removal of the asset from the pipeline recasts the cessation of enrollment as the start of Roche’s retreat from the candidate. Roche invested in the programs in the belief a molecule that simultaneously binds to CD3 on cytotoxic T-lymphocytes and HLA-A2 MAGE-A4 on tumor cells could orchestrate an anti-cancer immune attack. As MAGE-A4 is overexpressed by a variety of cancer cell types, the mechanism is potentially applicable to a range of tumors. The attributes of MAGE-A4 have made it a popular target for TCR T-cell biotechs, with Immunocore and its sibling Adaptimmune among the companies to go after the protein. Adaptimmune is closing in (PDF) on a filing for FDA approval of its first-generation MAGE-A4 candidate. Roche disclosed the MAGE-A4 news as part of a pipeline update that saw it punt two other programs. The list of castoffs includes zinpentraxin alfa, also known as PRM-151 and RG6354. Roche previously stopped a phase 3 trial of the candidate in idiopathic pulmonary fibrosis early because the study looked on course to fail.  Now, the drugmaker has stopped work on myelofibrosis, too. Roche acquired the drug candidate in the 2019 takeover of Promedior, which cost it $390 million upfront. Removing the myelofibrosis program from the midphase pipeline leaves Roche without active clinical programs involving zinpentraxin alfa. Finally, Roche also used the update to disclose the removal of a geographic atrophy program RG6312 from its phase 1 pipeline. Since RG6312 entered the clinic in 2020, the Big Pharma has suffered setbacks in its pursuit of the eye indication, failing a phase 3 trial in 2017 and dropping galegenimab last year. But it still has two shots on goal, including a Lineage Cell Therapeutics candidate that recently entered phase 2.

Over the past few years, Roche has released news about its AKT inhibitor ipatasertib in drips — most of them negative. The drug yielded mixed data in a key prostate cancer trial, Phase III flops in triple-negative breast cancer forced the pharma giant to pull the plug there, and in mid-2022 Roche trimmed two more early-stage indications in prostate cancer after completing the trials. Now, the last piece of the program is gone. Roche is officially scrapping the combination of ipatasertib and abiraterone, which was in a Phase III trial for first-line castration-resistant prostate cancer. It’s one of several late-stage programs Roche is sweeping out of the pipeline in its Q4 housecleaning exercise, alongside a trio of Tecentriq combos, the failed Alzheimer’s candidate gantenerumab and a drug for idiopathic pulmonary fibrosis. Separately, the company is dropping a Phase I compound for acute graft-versus-host disease. A Roche spokesperson confirmed to Endpoints News that “we don’t have any further projects ongoing with ipatasertib.” Although the Phase III IPATential150 study met its co-primary endpoint of radiographic progression-free survival in June 2020, it missed the key endpoint of overall survival at the second interim analysis. The spokesperson added that the safety profile of the ipatasertib/abiraterone combo was consistent with that observed at the primary analysis. Designed to block the PI3K/AKT pathway, ipatasertib arose from a partnership that Roche’s Genentech struck with Array BioPharma before Pfizer bought them out, and once inspired high hopes as a targeted approach. In the same presentation, Roche disclosed that it slammed the brakes on a Phase III study in idiopathic pulmonary fibrosis after a recent futility analysis suggested it’s unlikely to meet the primary endpoint. RG6354, which is also dubbed PRM-151 or zinpentraxin alfa, was the lead drug from Roche’s 2019 buyout of Promedior , for which it paid $390 million in cash upfront. Despite the setback, Roche still lists that program as a potential drug for myelofibrosis, with a filing expected in 2025 or later. Then there are three Phase III trials for the PD-L1 inhibitor Tecentriq being cut, in frontline metastatic urothelial carcinoma (Tecentriq + chemo), second-line non-small cell lung cancer (Tecentriq + Cabometyx) and second-line HER2-positive, PD-L1-positive metastatic breast cancer (Tecentriq + Kadcyla), respectively. Also exiting the pipeline are trials for gantenerumab, an anti-amyloid antibody, in preclinical Alzheimer’s and prodromal to mild Alzheimer’s — a reflection of Roche’s previously disclosed decision to stop all studies in the wake of a Phase III failure . Finally, Roche said it’s shutting down an IL-22 fusion protein, known as RG7880 or efmarodocokin alfa, that was being tested for the prevention of acute graft-versus-host disease in patients undergoing bone marrow transplant. The spokesperson cited “strategic reasons” for discontinuing the development, noting that “safety did not play any part in this decision.” Data from the Phase Ib study will be published.