New Pill Offers Hope Against Pancreatic Cancer 

A new pill can reportedly double survival in early pancreatic cancer trials, raising cautious optimism about a disease that has long resisted treatment. Revolution Medicines’ daraxonrasib targets KRAS, a gene that supplies instructions for the development of the K-Ras protein which is essentially a switch for controlling cell division, growth, and death. 

Daraxonrasib belongs to a class of targeted therapies dubbed RAS inhibitors, designed to act on the KRAS gene and disrupt a genetic mutation found across multiple cancer types. The biotech company behind the novel treatment will release its full Phase 3 results at the upcoming American Society of Clinical Oncology meeting. 

Pancreatic cancer has a five-year survival rate of just 3% after spreading, and most patients are not diagnosed until it has already advanced significantly. The most common form, pancreatic ductal adenocarcinoma, is one in which KRAS mutations are present in over 90% of cases. KRAS mutations also arise in 40 to 45% of patients with colorectal cancer and up to 30% of non-small cell lung cancer patients. 

Phase 1 and 2 results from April showed a median overall survival of 13.2 months on daraxonrasib, against 6.7 months on standard chemotherapy. Emil Lou, a medical oncologist and professor at the University of Minnesota Medical School, called it extraordinary that survival had exceeded one year. Participants had already undergone prior treatment before receiving the drug, which was administered as a second-line therapy. 

Among the 26 patients who carried the dominant KRAS variant seen in pancreatic ductal adenocarcinoma (PDAC), over a third saw measurable tumor shrinkage of at least 30%. Median survival reached 13.1 months with 8.5 months of progression-free survival in the same group. 

On the other hand, the patients suffered side effects such as rash, which affected 90% of participants, around 50% reported diarrhea or gastrointestinal inflammation, and about 30% experienced serious adverse reactions. 

KRAS has a smooth exterior that offers no binding sites, which, coupled with its location deep inside the cell, has led the medical industry to regard it as ‘undruggable’. Siolas described the challenge as finding a compound shaped to the gene’s unusual geometry that could also cross into the cell’s interior. 

In 2013, researchers found a previously undetected structural groove within the KRAS molecule, which opened the door to drugs like daraxonrasib. Jaffee noted that daraxonrasib works across multiple KRAS mutation types, so doctors can prescribe it without testing which variant a patient has. 

Practical obstacles remain, however. The FDA granted limited approval with expanded access in late April but many physicians still cannot prescribe the drug. Lou also notes that most patients are treated in community settings rather than academic hospitals, and said the gap in resources raises access concerns. 

Pricing is also unresolved, and treatments in this drug class have typically carried monthly costs well into the five-figure range. Jaffee compared pancreatic cancer’s potential trajectory to HIV, which became manageable once researchers found ways to target it across multiple biological pathways. 

The drive to develop new classes of cancer treatments is gaining momentum, and with biomedical firms like Calidi Biotherapeutics Inc. (NYSE American: CLDI) also reaching their own milestones in developing oncolytic virus therapies indicated for different cancers, the future of cancer treatment indeed looks bright. 

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