When a cancer drug enters the FDA approval pipeline, doctors and patients across the country watch closely, hoping for any sign that the drug may offer efficacy. But even if early results are positive, the drug will only be available to those enrolled in clinical trials who fit criteria needed by the FDA for final approval—a process that can take years—time some patients don’t have.
Access to unapproved drugs outside of clinical trials, commonly known as “compassionate use,” offers patients two additional avenues to receive drugs, explains Mary Lynn Carver, director of oncology public affairs for AstraZeneca.
“Under compassionate use, drug companies may have expanded access programs when a large number of patients are requesting a drug, or ‘single patient access’ when a physician requests a drug for one specific patient,” Carver explains.
The expanded access program, such as the one AstraZeneca opened for its lung cancer drug Iressa® (gefitinib) before its accelerated approval, sets a protocol that is less rigid than a clinical trial, allowing much broader participation by patients. Indeed, Carver says that by the time Iressa received limited approval in May 2003, more than 24,000 patients had received the drug through the expanded access program. But after a phase III trial failed to show an overall survival benefit, the FDA revised the labeling of Iressa in June 2005 to restrict its use to patients currently benefiting from the drug or those enrolled in a clinical trial. Some say this extensive use of an unproven drug led to the beginning of the FDA’s tightened control over early access to unapproved cancer drugs.
The FDA began permitting compassionate use programs in 1987 in response to the AIDS epidemic. Since then, the programs have become an emotional and complicated issue for the drug companies, who are bound by FDA regulations as to when and to whom they can give the drugs; doctors; and desperate cancer patients who may be dying as they wait for a drug that could extend if not save their lives.
The issue has escalated as preliminary results of new targeted therapies are released, since one drug may provide a mechanism that can be used against a number of different cancers. When early results for Gleevec® (imatinib) were announced in 2001, phone lines to maker Novartis were flooded by thousands of patients hoping to get the drug under the accelerated approval program. Since then the drug was granted full approval for adult CML in 2003 and accelerated approval for pediatric CML and gastrointestinal stromal tumor. The same public response has occurred at drug companies across the country as early results of the newest cancer therapies have been announced.
“Every company has its own guidelines,” Carver says. “At AstraZeneca we agree to look at a drug for compassionate use once it is through phase II and we have an idea of safety and efficacy and if it’s in an area where there is high unmet need. A lot depends on the clinical trials and whether they are large and can take care of many patients since the FDA approval is ultimate access to get the drug into doctors’ hands.”
Some patient advocates say it’s not enough and they are asking the FDA to make access to unapproved drugs easier for those who have no other options.
Steven Walker became an expert on compassionate use when his wife Jennifer McNeillie was diagnosed with stage 4 colon cancer in December 2000. The drug was Erbitux™ (cetuximab), which McNeillie began in September 2002 in a phase II trial in Orlando. By the time she began the Erbitux trial she had tumors in her ovaries, liver, lungs and peritoneal cavity.
“She had a miraculous response to Erbitux,” says Walker, an environmental consultant. “She went from being really sick to going back to work in two weeks. Almost all the tumors were gone.”
After six months on the drug, despite the fact that her overall tumor burden was essentially gone, McNeillie developed a small lesion on her liver, which, according to the trial’s protocol, meant she had to be removed from the trial.
“She was able to get into another clinical trial for Erbitux for symptom control but it took seven weeks,” says Walker. “By that time, it was too late.” McNeillie died in June 2003. Erbitux was given accelerated approval for use in advanced colon cancer in February 2004.
Today Walker remains active with the Abigail Alliance, an organization founded by Frank Burroughs in 2001 to help create wider access to developmental cancer drugs. Burroughs’ daughter Abigail died of advanced head and neck cancer in June 2001 at the age of 21 after a battle to get Erbitux, which targets the epidermal growth factor receptor, on compassionate use after her oncologist told the family about encouraging results from early trials for the drug. Abigail died before being accepted into a compassionate use program. ImClone Systems plans to submit a supplemental new drug application for the use of Erbitux in treating head and neck cancer before the end of the year.
Walker and others with the Abigail Alliance (www.abigail-alliance.org) have petitioned the FDA to approve a new tiered approval process that would begin with an initial approval before accelerated approval and final approval to make developmental life-saving drugs more readily available. For more information on compassionate use, go to