FDA’s Expedited Review of Drug Could Be a ‘Game Changer’ for Pancreatic Cancer

Hoping to develop better methods to treat pancreatic cancer — one of the most aggressive, deadly types of cancer — the United States Food and Drug Administration (FDA) is speeding up its review of a drug called daraxonrasib to see if it may deliver better results for patients.

Pancreatic cancer is one of the toughest cancers to diagnose and treat, explains oncologist Christopher Lieu, MD, a professor of medical oncology at the University of Colorado Anschutz Department of Medicine and associate director of clinical research at the CU Anschutz Cancer Center. For decades, scientists have struggled to develop better treatments, often having to rely on chemotherapy — a treatment that works for some but not for many others.

Initial research suggests that daraxonrasib, a targeted drug therapy, could potentially be more effective than chemotherapy. However, before the FDA can deem the drug to be a safe and viable option, the agency must conduct a thorough review. This approval process typically takes 10-12 months, but thanks to a new federal pilot program, the FDA is expediting the process to take one to two months following the filing of a complete application.

“There are certain diseases where getting access to promising drugs may mean the difference between life and death, and pancreatic cancer is an example of this,” Lieu says. “There are not enough treatment options, and our patients don’t have the luxury of waiting years for any regulatory agency to review data. The idea that the FDA has a pathway for accelerated review is important and exciting, but it’s a new program, so I think there’s still a lot we’ll have to learn from it.”

We recently spoke with Lieu about what is known about daraxonrasib, the lingering questions surrounding the drug, and the potential benefits and limitations of an expedited FDA review process.

The following interview has been edited and condensed.

How aggressive is pancreatic cancer, and why are additional treatments needed for it?

The five-year survival rates for pancreatic cancer — the percentage of people with pancreatic cancer who live at least five years after diagnosis — are dismal. It trends around 5% in the metastatic setting (meaning the cancer has spread to other parts of the body). One of the reasons that pancreatic cancer is difficult to diagnose and treat is because we don’t have effective screening tests. As a result, patients oftentimes are diagnosed with advanced stages of the disease, often when surgery is not something we can offer.

Traditionally, with pancreatic cancer, it’s been a one-size-fits-all treatment strategy of chemotherapy, which may help one patient but not three others, for instance. Meanwhile, they’re all experiencing the side effects. How much better would it be if we could apply a more personalized therapy and target the cancer?

Daraxonrasib is a more targeted therapeutic approach. Can you give an overview of how it works?

Over 90% of patients who are diagnosed with pancreatic cancer have a mutation in a gene called KRAS, which is one of three types of genes in the RAS gene family. There’s been decades of work trying to figure out how to target RAS, because we know that it’s one of the most commonly mutated genes in cancer. However, it’s been hard to design drugs that can target RAS, so it was traditionally thought that RAS was an undruggable target.

However, daraxonrasib is a drug that targets RAS. It’s called a RAS(ON) inhibitor. Essentially, the drug binds to the activating pocket of KRAS and shuts it down. It’s almost like if you have a bullhorn and you cover it up so no sound can escape. There’s a possibility that this targeted therapy for pancreatic cancer could work more effectively than chemotherapy, meaning it could be a treatment with potentially less toxicity.

How did you first hear about daraxonrasib, and what was your reaction to it?

When the drug was used in early-phase clinical trials, I started hearing about patients who were responding to the drug. Whenever there’s a significant response rate within a clinical trial, it captures everyone’s attention. My initial reaction was a lot of hope. The fact that the drug was effective at targeting RAS and there were positive responses to it was very exciting.

What are the potential side effects of daraxonrasib?

One of the downsides is that we know these drugs can sometimes be difficult to take. Just because it’s a targeted drug doesn’t necessarily mean that it’s always going to be well tolerated. We need to look at the potential toxicity of the drug.

We also have to look out for potential gastrointestinal side effects like nausea, vomiting, and diarrhea, as these are known effects of this class of medication.

What is still unknown about daraxonrasib?

The biggest unknown is what the actual impact of this drug is. When it comes to cancer medicine, there are three things we’re interested in. First, does the drug increase overall survival? That’s the ultimate outcome. We want patients living for a longer period of time, and it can’t just be a couple of weeks. It needs to be a clinically relevant extension of time.

Second, we’re interested in progression-free survival, meaning how long it takes for a cancer to grow while a patient takes the treatment. For daraxonrasib, we want to make sure that when we give this drug, it takes longer on average for a patient’s cancer to grow compared to standard chemotherapy.

Third, we’re looking at response rate. How many patients does the drug shrink cancer in? This is important because it’s not good enough to keep cancer from growing. We also want to shrink cancer, as that will help patients feel better.

Currently, we have early data in a small number of patients about these outcomes as it relates to daraxonrasib, but we don’t know what the outcomes will be in a much larger group of people and how it compares to chemotherapy.

The FDA awarded daraxonrasib a Commissioner’s National Priority Voucher, accelerating the reviewal process. What was your reaction to that decision, and what do you think are potential positives — and potential negatives — of an accelerated review?

The FDA process for approving drugs is extraordinarily important and complex. When a company submits a drug application to the FDA, it usually takes up to 10-12 months to review. It takes that long because you’re asking a lot of the FDA to review data and have discussions, and this pathway is trying to shorten that. The benefit of that is clear — if the data are positive and it allows patients to access a drug faster, that’s a win.

The potential unintended consequence of this is that you’re asking a lot of the FDA to review a tremendous amount of data in a short amount of time. I worry sometimes about the depth of the review whenever you expedite it, because you don’t want to miss important toxicity signals or make a call too early on a drug.

There are two things I believe in. First, I believe this is a good process, and anytime we can get faster access to drugs that benefit patients is a good thing. Second, if this drug is approved, it will be critically important for us to follow up and make sure that the drug is doing what we intended and closely monitor for toxicity.

To do this review in one to two months really stresses the point that there are some diseases where people can’t afford to wait. When it comes to pancreatic cancer, there is an unmet need within the disease, and the preliminary data suggests that daraxonrasib could be a game changer.

Overall, what would you most like for community members to know about this?

First, it’s important to know that the landscape of all cancers is changing in a good way. Personalizing treatments for cancer is something the public should understand, and the amount of drug development happening in cancer medicine is exciting. To fight cancer smarter should always be a national — and global — priority.

I also think this process is proof that the FDA truly cares about people who are suffering from disease, given that they’re willing to move things along as fast as possible. But the FDA’s job is tough, because they also need to make sure that what they’re approving works and doesn’t hurt people — which is not as easy as it sounds. I think it shows the FDA is not trying to be a barrier but rather a screen door for everything to pass through.