The US approves a drug against a protein until now "impossible" to attack of pancreatic cancer

BarcelonaIf there were a switch to halt the growth of tumor cells in the pancreas, it would be found in the RAS protein. Like the head of a factory, this gene sends cells the order to grow and multiply. In 90% of pancreatic cancer cases, this mechanism is altered practically from the earliest stages of development and the instruction remains permanently activated, which becomes one of the main drivers of uncontrolled growth. For decades, RAS was considered an "impossible to block" therapeutic target (in English, undruggable) due to its chemical structure. Now, the Food and Drug Administration (FDA) has approved Rasonque (daraxonrasib), a drug that manages to act on multiple forms of RAS to interrupt growth signals.

The American biotechnology company specializing in oncology, Revolution Medicines, has developed the first targeted therapy against RAS for metastatic pancreatic cancer. The achievement is revolutionary: it has received the green light from the FDA six and a half months before the deadline set by the agency itself and opens the door to a new treatment option for patients with advanced disease. Rasonque is a tablet taken once a day, which makes treatment easier for patients. The results of the phase 3 trial – presented in early June – with half a thousand adults with previously treated metastatic cancer show an improvement in median overall survival to 13.2 months compared to 6.7 months with standard chemotherapy. That is, almost double.

Pancreatic cancer is one of the deadliest tumors due to its typically late detection, the aggressive course of the disease, and historically limited treatment options. Its location, behind the stomach and in contact with the duodenum and bile duct, hinders early detection and often leads to diagnosis when the disease is already advanced. And, although it is not the one with the highest incidence, it is one of the tumors with the highest mortality rate in relation to the number of cases and presents one of the lowest survival rates. In Catalonia, approximately 12% of patients are still alive five years after diagnosis.

"It's a first piece of good news about what will surely be a change in therapeutic strategy against pancreatic cancer. The results are very exceptional, we had never achieved them until now," says the head of the Medical Oncology Service at the Hospital Clínic de Barcelona, Teresa Macarulla. She is one of the leading international references in the research and treatment of pancreatic cancer and considers it a drug that has much better results than what has been achieved so far in this disease. "The approval is very important: patients need new treatments, because the existing ones are few and with very limited activity," she admits.

A new era on the horizon

The activity of Rasonque can be simplified as follows: it blocks the cell with RAS, which has an advantage over healthy cells because it has the mutated gene, and limits its uncontrolled reproduction. "What we experts foresee is that in a few years RAS inhibitors, not only this drug but also many others to come, will be part of the therapeutic scenario for all situations of pancreatic cancer: during surgery, as a first treatment, as a second treatment...", states Macarulla.

The drug is indicated for adults with metastatic pancreatic cancer who have already received at least one treatment or who, due to their health status, cannot receive a combination of several drugs at once. The FDA has highlighted that the authorization offers a new treatment option for patients with a particularly difficult-to-treat cancer. "Today's approval offers a new option for patients facing an extraordinarily difficult and historically challenging cancer to treat," says the agency's acting commissioner, Kyle Diamantas, who emphasized that the FDA's goal is to make new treatments available to patients as soon as possible.

Macarulla is cautious before predicting when this drug might reach Catalan patients, considering that the approval is limited to the United States and it will be necessary to wait for Revolution Medicines to present it to the European Medicines Agency (EMA) and, if authorized, for member states to purchase and dispense it. "Doctors and researchers will fight to ensure access as soon as possible," says the expert, who points out that for now there are clinical studies with this drug or similar ones. Regarding adverse effects, the most frequent are skin rashes, diarrhea, inflammation of the oral mucosa, nausea, fatigue, vomiting, abdominal pain, bloating, loss of appetite, and bleeding.

A fast track approval

The FDA justifies advancing authorization due to the desire to accelerate the arrival of innovative treatments for patients and reduce waiting times. In this case, Rasonque had received several FDA designations aimed at facilitating and, in some cases, accelerating its development and review. The Innovative Therapy designation is awarded to treatments that show signs of offering a substantial improvement over available options; the Orphan Drug designation is for drugs intended for rare diseases, and Priority Review allows the agency to review the application in a shorter timeframe than usual.

These designations do not equate to approval nor guarantee that the drug is more effective or safer, but they do allow for the acceleration of its development and review. However, in May, the agency had already allowed expanded access to the drug so that some patients could receive it before its final approval. "This drug has shown unprecedented results in an area with a large unmet need," states the director of the FDA's Center of Oncological Excellence, Angelo de Claro.

Revolution Medicines is confident that its drug will transform the way pancreatic cancer is treated and generates "optimism" for even greater advances. "We continue to collaborate with global regulatory authorities with the aim of expanding and accelerating the reach of Rasonque," assures the company's chief executive officer and president, Mark A. Goldsmith.