NEWS

Demand Grows for Early Access to Promising Cancer Drugs

Joyce Baldwin

In recent years, expanded access programs have allowed thousands of patients with cancer to gain access to investigational drugs before they are approved by the U.S. Food and Drug Administration. Prior to the mid-1990s, patients who had exhausted all standard avenues of treatment were able to obtain investigational drugs only on a case-by-case basis.

Expanded access programs are an extension of more traditional compassionate use programs and allow patients to receive investigational drugs earlier than phase III of the clinical trial process. (See sidebar, p. 1669, for descriptions of various ways patients can gain access to investigational drugs.)

Patient advocacy groups have played a key role in the growth of expanded access programs. Over the last decade, the number of advocacy groups for cancer patients has swelled to several hundred, and members of these groups have become increasingly educated about the intricacies of clinical trials and expanded access programs. These advocacy groups have been pressuring drug companies to supply new drugs at an even earlier stage of the clinical trials process.

Programs that provide investigational drugs to cancer patients were inspired by similar programs for AIDS patients, said Jane Reese-Coulbourne, a consultant to pharmaceutical companies, the Susan G. Komen Foundation and the National Cancer Institute. "Because there were so few approved AIDS drugs, people wanted access to the drugs that were in development," she said. "The AIDS community has brought expanded access [programs] through many changes over the years."

On the cancer front, Reese-Coulbourne has been involved with the development of expanded access programs for Herceptin (trastuzumab), Gleevec (imatinib mesylate), Eloxatine (oxaliplatin), and Iressa (gefitinib).

Herceptin was the first cancer drug that attracted attention from patients, said Reese-Coulbourne, who is the former executive vice president of the National Breast Cancer Coalition. When patient advocacy groups learned that Herceptin was showing promise in clinical trials, they pressured the manufacturer, Genentech, to provide the drug early to certain patients, she said. To convince the company—which did not have an extended access policy—to make the drug available sooner than FDA approval, activists chained themselves to the front gates of Genentech and flooded the company with faxes and telephone calls.

"From a PR standpoint, it was a horror show," said Reese-Coulbourne. The National Breast Cancer Coalition helped Genentech develop an expanded access policy and the program was approved by the FDA.

The decision to offer cancer drugs to patients through an expanded access program is entirely up to the pharmaceutical company, but the company does have to submit a copy of its protocol to the FDA. As long as the agency has no objections, the company can proceed with the program. The companies must then regularly report safety data to the FDA. Expanded access programs can be administered in-house by the drug company, but usually a company contracts the service out to a group has experience in clinical trial recruitment.

In deciding whether to proceed with an expanded access program, drug companies must weigh the risks and benefits of providing drugs outside a clinical trial while still accruing patients for the trial, which will evaluate the drug’s safety and efficacy. Currently, physicians collect only safety data for drugs given to patients in an expanded access program.

Another issue to consider is the drug’s availability. "The most important first step in use of a drug outside a clinical trial is for the company to agree to make that drug available," said Patty Delaney of the Office of Special Health Issues in the Cancer Liaison Program of the FDA.

With Gleevec, a drug used to treat the rare but life-threatening chronic myeloid leukemia, Novartis Oncology treated thousands of patients through their expanded access program.

"We had to go to commercial manufacturing capabilities at a time when the drug wasn’t approved yet in order to provide the drug. Resource-wise, it was an intensive, intensive effort," said Barbara Kennedy, executive director of oncology scientific operations at Novartis Oncology.

"Both the personnel resources and the funding was going for this [expanded access program] as opposed to other projects," she said. "We have a lot of other drugs that are good and important, and there’s the risk of putting a lot of resources in that area and having an impact on other things." But, she noted that the company benefited from "a lot of goodwill from the patients."

Despite the potential benefits to a company, expanded access programs are costly. Gerard Kennealey, M.D., vice president of oncology clinical research at Astra-Zeneca, said that it cost their company "in the eight figures" to carry out an expanded access program for the cancer drug Iressa. The program has provided the drug free of charge to 13,000 patients in the United States and 5,000 additional patients worldwide.

Kennealey, who headed the team that developed the expanded access program for Iressa in the United States, said their company did what was necessary to make the drug available to patients who needed it. "Nobody badgered me about budget issues," he said. "The company was really committed to the drug and to making it available to patients to whom it could provide benefit."

But companies have been mindful of the impact that expanded access programs may have on patient accrual to clinical trials. Through an expanded access program, patients can be assured of receiving the drug, not a placebo or control treatment, a factor that may make them reluctant to join a clinical trial.

"If people start to believe a drug works before we really have the data, then they are going to say, ‘I don’t want to be randomized to standard treatment, I want the new drug,’" said Reese-Coulbourne. "Some doctors, not many, but some, will start to also believe that. They may think, ‘for this patient I don‘t want to risk putting them on standard treatment. I want them to get new stuff.’ They will say the patient is not eligible for the clinical trial and recommend they sign up for expanded access."

With Iressa, Kennealey noted that the expanded access program "did not detract from the clinical trial because the trials filled so quickly and there was such a huge unmet need in patients with advanced non-small-cell lung cancer."

"The biggest benefit to us was that we amassed a large amount of safety data," he said. "So that now when we are going to take the drug to market, we are even more comfortable with the safety profile of the drug than we would have been with just the clinical trials that we were doing."

Although pharmaceutical companies may be primarily concerned with the economics of expanded access programs, they need to understand that the information relayed to the public may be interpreted a little differently, suggested Abbey Meyers, president of the National Organization for Rare Disorders (NORD). "When companies try to build up their stock on Wall Street and they release glowing reports that they have a cure for the sake of investment, they don’t realize that that same message gets to the patient community," she said. "So patients begin to believe that there is some miraculous drug, and they want to have immediate access.



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Abbey Meyers

 
"They don’t understand that while the drug is experimental, we still don’t know everything and [patients] may be exposing themselves to particular dangers," she continued. The staff at NORD handles about 9500 telephone calls monthly, most of which are from patients. NORD has overseen eight expanded access programs, including one for the drug Iressa.

While certain issues still need to be worked out, some people feel that, in the long run, expanded access programs will benefit drug development. "People who enroll in an expanded access program represent a broader slice of life than people in a clinical trial because selection criteria are looser," said Nancy Roach, a volunteer on the board of directors of the Marti Nelson Research Foundation. "So you may get a more realistic picture of how a drug is going to react and can sniff out safety side effects that you wouldn’t see in a trial of 300 or 1000 but would see in an expanded access program."

Expanded access programs are clearly becoming an important public policy issue with implications for the clinical trial arena.

"You’re going to be hearing a lot more about this," said Reese-Coulbourne. "Oncology patients who have exhausted all standard avenues of treatment sometimes view the drugs as holding the promise of a miracle cure. We are looking at many new drugs coming out of the pipeline that seem to have few harsh side effects and great efficacy promise. For an end-stage cancer patient, that is an easy, personal cost/benefit analysis. They will want these drugs."


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