FDA Approves Rasonque For Pancreatic Cancer

Helene Rubin was enjoying life after retiring from her job as an urban planner until she received a devastating diagnosis. She had developed pancreatic cancer, which is widely considered one of the toughest cancers to treat.

Rubin took the traditional chemotherapy treatment, but it didn’t seem to be working because the aggressive cancer had spread to her lungs. An oncologist near Rubin’s home in New Jersey told her that she should look for a clinical trial focused on pancreatic cancer.

Rubin learned that Memorial Sloan Kettering Cancer Center (MSK) was one of many sites running Phase 3 of a clinical trial for daraxonrasib, a new drug for people who no longer respond to at least one other form of treatment or aren’t candidates for multiagent systemic therapy.

The turnaround was amazing. The vibrant 83-year-old mother and grandmother was able to bounce back from the dreaded disease after taking daraxonrasib.

Because other trial participants worldwide saw successful results from daraxonrasib, the U.S. Food and Drug Administration (FDA) approved the breakthrough drug to strengthen the fight against pancreatic cancer.

Daraxonrasib, marketed as Rasonque, is now available by prescription in the United States. California-based Revolution Medicines developed the tablet taken orally once a day. The FDA’s approval means oncologists nationwide can prescribe this drug, and health insurers and Medicare will cover or subsidize the cost.

When it comes to groundbreaking drugs, acting FDA Commissioner Kyle Diamantas said the agency is committed to “moving with urgency, reducing unnecessary delays, and advancing innovative treatments that can make a meaningful difference in the lives of American patients and their families.”

Rasonque’s approval “provides a critical new option for patients facing an extraordinarily difficult and historically hard-to-treat cancer,” Diamantas said in a news release. “It is our fundamental duty to deliver more cures and meaningful treatments to patients as quickly as possible.”

Rasonque Targets KRAS Gene Mutations

Pancreatic cancer specialists say Rasonque’s success hinges on its ability to target and block multiple forms of RAS, a broad family of proteins that drives tumor growth in most pancreatic adenocarcinoma cases.

Within the RAS family is the KRAS gene, which acts as a molecular “on-off switch” that regulates normal cell growth and division. When the KRAS gene mutates, the switch gets stuck in the “on” position and sends signals that tell cells to grow and divide out of control. This is what leads to tumor formation and cancer development, according to cancer specialists.

KRAS is like a “shiny ball,” according to Dr. Shubham Pant, an international investigator for the Rasonique clinical trials and a professor in the Department of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center, one of the clinical trial sites.

“You can’t stick anything to it,” Dr. Pant said in an interview with Managed Healthcare Executive. “It just kind of slides off.”

Rasonque, however, binds directly to the KRAS mutations, which is why it’s considered a “first-in-class” multi-selective RAS (ON) inhibitor. According to its developer, Revolution Medicines, Rasonque binds to and shuts off multiple forms of active, mutated KRAS proteins.

“For the first time, patients have an approved targeted medicine designed to directly inhibit the main cause of pancreatic cancer, RAS, which has been one of the most intractable disease targets since its discovery decades ago,” Dr. Mark A. Goldsmith, chief executive officer and chairman of Revolution Medicines, said in a news release.

Researchers and oncologists say KRAS mutations drive over 90 percent of pancreatic cancers because they send signals that cause uncontrolled cell growth. For years, the experts have considered KRAS mutations nearly impossible to treat with drugs—until now.

Because Rasonque directly targets KRAS mutations and shuts down these signals, “patients usually feel the difference quite quickly,” Dr. Eileen O’Reilly, who led the Phase 3 clinical trial for Rasonque at MSK, said in a news article. “Their pain is better. They eat better and feel less fatigued.”

Phase 3 Trial Results

The global Phase 3 clinical trial involved 500 adults who had previously been treated for advanced pancreatic cancer. About half of the trial participants were randomly assigned Rasonque, and the other half received chemotherapy. The trial was conducted at multiple institutions and cancer centers worldwide.

The researchers found that Rasonque significantly improved treatment outcomes, both statistically and clinically, compared to standard chemotherapy. For example, Rasonque improved median overall survival to 13.2 months compared to 6.7 months for standard chemotherapy.

“This is happening across a broad selection of patients because KRAS mutations are present in nearly every pancreatic cancer case and are important to the growth and metastasis of this disease,” Dr. O’Reilly said. “It’s very encouraging that we are seeing these kinds of results for people with pancreatic cancer on a large scale.”

How Rasonque Works

Unlike traditional chemotherapy, which blindly attacks all fast-growing cells in the body, Rasonque is more specific:

1. Once swallowed, Rasonque binds to a naturally occurring protein inside cells called cyclophilin A.

2. Together, they form a complex that locks onto the active, “switched-on” forms of RAS proteins, such as KRAS.

3. After attaching to the RAS proteins, the Rasonque complex blocks the mutant pathways that drive cancer cells to multiply rapidly. This starves the tumor, cuts off its growth, and causes cancer cells to die.

Rasonque’s ability to stop cancer cells from growing allows people diagnosed with pancreatic cancer to live longer.

“To date in my career, I have not seen this level of benefit from any single anti-cancer drug in this disease,” Dr. O’Reilly said.

Rasonque’s Side Effects

Like other drugs that treat cancer, Rasonque carries risks of serious side effects, including:

The side effects were severe enough to stop treatment in 1.2 percent of trial participants who took Rasonque compared with 11.2 percent of those on chemotherapy, according to the clinical trial results.

Rubin said she was hospitalized for a short time after experiencing gastrointestinal side effects from Rasonque.

“But I wanted to stick it out,” Rubin said, “both to see if the drug could help me and to contribute to helping other people with this disease.”

Rubin began to improve after Dr. O’Reilly and her team lowered Rubin’s dosage. Although she still has some side effects, Rubin said, “they don’t interfere with what I do or how I feel most of the time. I’m really grateful for the clinical trial because the drug has worked terrifically for me.”

Source Links:

https://www.mskcc.org/news/how-daraxonrasib-could-improve-pancreatic-cancer-treatment-offering-new-hope
https://www.fda.gov/news-events/press-announcements/fda-approves-first-class-targeted-therapy-metastatic-pancreatic-cancer
https://www.mdanderson.org/cancerwise/targeting-the-kras-mutation-for-more-effective-cancer-treatment.h00-159458478.html
https://www.yahoo.com/news/science/articles/fda-approves-rasonque-pancreatic-cancer-202550455.html
https://www.drugs.com/rasonque.html
https://ir.revmed.com/news-releases/news-release-details/us-fda-approves-revolution-medicines-rasonquetm-daraxonrasib/