The Food and Drug Administration said on Friday that it would permit some patients with deadly pancreatic cancer to receive early access to a promising, highly coveted drug.
The treatment, daraxonrasib, taken as three pills a day, is not yet approved for use. But many patients have been desperate to try it. The drug recently generated the most encouraging clinical trial results the pancreatic cancer field has seen.
Revolution Medicines, the Silicon Valley company developing the drug, requested permission to give it to patients under a regulatory pathway known as expanded access. Until now, no one has received the experimental drug outside of clinical trials, where patient demand far exceeds the limited number of slots, according to the company.
The F.D.A. said that patients with metastatic pancreatic cancer that has been “previously treated” would be eligible for the program. It was not immediately clear how soon patients could start taking the drug if they qualify.
Cancer of the pancreas — the gland buried deep in the abdomen that is involved in digestion and blood-sugar regulation — has one of the grimmest prognoses in oncology, with many patients dying within months of diagnosis. The disease kills more than 50,000 Americans a year, accounting for about 8 percent of cancer deaths in the United States.
The few available treatment options often do little to help. Only 3 percent of people whose pancreatic cancer has spread to distant parts of their body live for five years after being diagnosed.
Many patients and families have pleaded for daraxonrasib to be offered through expanded access, saying they do not have time to wait for the drug to win regulatory approval. The Trump administration has designated the drug for a fast-tracked review and could approve it later this year.
“We are in a situation where Ian could be dead before this comes on the market,” said Emily Solari, whose husband, Ian Spradlin, 46, has metastatic pancreatic cancer.
Mr. Spradlin, who has already tried three lines of chemotherapy and two experimental drugs, said in an interview last weekend that he would be eager to try daraxonrasib under expanded access if he could get it that way.
“I want to have more time with my kids,” he said.
Expanded access, also sometimes known as compassionate use, is meant to bridge the gap of months or years between when a drug shows promise in studies and when it becomes available on the market. It is intended for the sickest, most desperate patients who have no good standard treatment options. Typically the company developing the drug provides it for free.
The F.D.A. receives hundreds of requests for early access annually. Doctors can seek it for individual patients if a drugmaker agrees to provide the drug. The F.D.A. said it granted more than 99 percent of these requests. Or, as with daraxonrasib, expanded access programs can be run for larger groups of patients.
In recent months, the F.D.A. has been criticized by patient groups and doctors who were discouraged by delays and some denials in approvals of drugs, largely for rare diseases. Dr. Marty Makary, the agency’s commissioner, has responded by promising speedier reviews for some drugs.
Last month, Revolution wowed the field when it announced that daraxonrasib doubled survival time in a late-stage clinical trial. People who received the drug lived for more than 13 months, compared with less than seven months for those who received chemotherapy, the company said in a news release.
The study enrolled 501 patients with metastatic pancreatic cancer who had already tried one line of chemotherapy. A gain of six months of life expectancy is unheard-of for people at that phase of the disease.
Researchers plan to present the data later this month at a cancer conference in Chicago. The findings have not yet been published in a peer-reviewed medical journal.
Daraxonrasib often causes side effects like rash, diarrhea, fatigue and nausea. Several patients who took the drug in clinical trials said that the side effects, including raw, split fingertips, could be harsh.
A high-profile participant in the drug’s clinical trials is Ben Sasse, a former Republican senator from Nebraska who disclosed that he had pancreatic cancer late last year. In a recent video interview in the New York Times Opinion section, he attributed a rash on his face to a side effect of the treatment. He said the drug had shrunk his tumors and allowed him to cut back on pain medicine.
In an interview this week, Dr. Mark Goldsmith, Revolution’s chief executive, said that the company had been fielding a flood of inquiries from patients pleading for the drug. He said that whenever clinical trial slots for the drug opened, they often got snatched up the very same day.
“The demand for daraxonrasib has been very high for several years now, and only getting higher every time we show any data,” Dr. Goldsmith said.
“It’s a desperate situation because it is a disease that is relentless,” he said. “What we can do about that is move with haste.”
Daraxonrasib targets a mutated protein known as KRAS that fuels the growth of nearly all pancreatic cancers, as well as many cancers of the lung and colon. Developing a drug that homes in on KRAS was long thought by some researchers to be impossible.
Revolution, along with several other companies, is testing other drugs in earlier stage clinical trials that work similarly to daraxonrasib. But there are not enough study slots to accommodate what pancreatic cancer specialists described as an onslaught of requests from patients. They said they hated to tell patients that daraxonrasib was all but unavailable.
“We have a huge waiting list,” said Dr. Nilofer Azad, a pancreatic cancer specialist at Johns Hopkins Medicine.
“I daily get emails from people around the world,” Dr. Azad said. “There are people who fly here from overseas just so we know them,” she added.
The promising data on daraxonrasib has only increased patient demand.
On Wednesday, Raven Zachary, 52, of Portland, Ore., met with an oncologist for the first time after receiving a preliminary diagnosis of metastatic pancreatic cancer. He brought with him a printout of his 19 most urgent questions.
The question at the top of his list: “What about daraxonrasib? Am I eligible based on my condition and do you have access?”
In interviews, patients and families said they understood that daraxonrasib was not a cure. They said they had realistic hopes about what it might be able to give them: more months with their families, or the chance to travel without being tethered to a chemotherapy infusion chair every two weeks. They said they were willing to accept the risk of side effects, or that it might not work as well as the clinical trial results suggested.
“Every month that that drug is delayed means that I have to get chemo two more times,” said Dr. Ronald Silvestri, 77, a retired pulmonologist in Natick, Mass. He has metastatic pancreatic cancer and has already received 32 rounds of chemotherapy while trying unsuccessfully to get into a clinical trial. “And it’s getting harder and harder for me to tolerate it.”
Pathways for desperate patients to get unapproved drugs have been around for decades, and have sometimes prompted fierce battles over how quickly, and for whom, the drugs should be made available. The process was formalized in the 1980s, when dying AIDS patients pushed for early access to treatments.
In 2021, patients with amyotrophic lateral sclerosis, or A.L.S., pressured Biogen, the company developing a drug for a rare genetic form of the neurodegenerative disease, to offer it through expanded access. The patient at the center of the campaign, Lisa Stockman Mauriello, was shut out of a clinical trial because of when she had been diagnosed. But she ultimately received the drug via expanded access just days before she died and nearly two years before it won F.D.A. approval.
Today, the case of daraxonrasib has all the ingredients — a deadly disease, a lack of decent treatment options for patients and clear data indicating the drug works — that “bode in favor of an ethical default for the company to set up one of these programs,” said Holly Fernandez Lynch, a bioethicist at the University of Pennsylvania.
The F.D.A.’s sign-off applies only domestically; requests for patients must be placed by a doctor licensed in the United States. At least for now, that restriction will prohibit most desperate patients in other countries from getting the drug.
Cynthia Ataefe, 66, of Buenos Aires, has metastatic pancreatic cancer and wants to try the drug. But she is too sick to travel for a clinical trial, even if she could get into one, according to her daughter, Cecilia Gerson, who lives in New York.
Ms. Gerson said earlier this week that the family was pinning its hopes on expanded access. “I still hope that somehow we will get the drug in time,” she said.
Source:
www.nytimes.com
