RevMed nears EU okay for pancreatic cancer drug Rasonque

Revolution Medicines is likely just weeks away from getting EU approval for its oral RAS inhibitor Rasonque as a treatment for pancreatic cancer, after the drug was recommended by the EMA's human medicines committee.

The CHMP has backed Rasonque (daraxonrasib) for adults with metastatic pancreatic adenocarcinoma who have received at least one previous treatment – the same indication that was cleared by the US FDA in August.

The positive opinion is based on phase 3 results with Rasonque from the RASolute 302 trial that caused a stir at this year's ASCO cancer congress, with a doubling in overall survival (OS) and progression-free survival (PFS) compared to chemotherapy and big improvements in quality-of-life scores.

The outcome was remarkable, particularly as metastatic pancreatic adenocarcinoma is a notoriously difficult-to-treat cancer with a low survival rate.

"People with metastatic pancreatic adenocarcinoma whose disease has worsened after prior treatment have limited treatment options and a poor prognosis," said the EMA, which granted Rasonque an expedited, phased review – which cut its assessment time from 210 days to less than 150 days – as a high-priority medicine that could address this unmet medical need.

"Given the seriousness of the disease, [and] the limited efficacy and substantial toxicity of standard-of-care chemotherapy, there is a need for better treatment options for these patients."

The RAS protein is a key driver for many tumour types, including the majority of pancreatic cancers. For many years, it was considered an 'undruggable' target, until RevMed solved the problem with daraxonrasib, constructed by binding RAS to a protein called cyclophilin A to form a complex that can attach to the RAS protein and block its activity.

The pan-RAS category is pretty crowded, with more than a dozen drug candidates in clinical testing, but Revolution seems to have a healthy first-mover advantage with other trials underway in pancreatic adenocarcinoma, as well as non-small cell lung cancer (NSCLC).

Those include the RASolute 303 trial in first-line pancreatic cancer, RASolute 304 in adjuvant treatment of tumours treatable with surgery, and RASolve 301 looking at first-, second-, and third-line treatment of metastatic NSCLC.

There has been some noise about Rasonque's slightly lower tumour response rate in patients with KRAS G12D mutations in RASolute 302, which analysts have suggested could open the door to competition from selective drugs like Verastem Oncology's VS-7375, which is in phase 3 for pancreatic cancer.

RevMed is, however, also developing a KRAS G12D-selective inhibitor, zoldonrasib, both as a monotherapy and in combination with Rasonque.