Federal approval of a new drug that slows the progression of AIDS but does not cure the disease was greeted today with a mixture of applause and reservation by specialists at Johns Hopkins Hospital and the University of Maryland Medical Center.
The U.S. Food and Drug Administration yesterday licensed dideoxyinosine, or DDI, which acts like AZT.
"It's wonderful to have another drug for this disease -- because it's an awful disease -- however, it's kind of an approval in a vacuum," said Dr. Judith Feinberg, an AIDS researcher at Hopkins.
"There really is no information to physicians about how to use this drug -- who should get it, what should your patient expectations be, is it as good as, better than or the equivalent to AZT? I just think the data are very, very thin and I'm troubled by that."
Dr. Jonathan A. Cohn, the director of the Adult HIV Program at the UM Medical Center, said DDI's licensing by the FDA "is reasonable" and that it's a distinct advantage to have more treatment options.
Until now, AZT has been the only other fully approved anti-AIDS drug.
"AZT by itself has been helpful," Cohn said. "It has prolonged the lives of many people, but it has lots of limitations. On the other hand, even though DDI has been studied in more than 22,000 patients, we don't really know how effective it is."
DDI has won approval as a treatment for patients with advanced acquired immune deficiency syndrome who don't respond to or can't tolerate AZT.
In giving DDI the green light, FDA Commissioner David Kessler said, "It is the victims of this dreaded disease who are uppermost in our minds as we make this announcement . . . it offers a new means of defense against the AIDS virus and brings hope to those who cannot benefit from AZT."
More than 180,000 Americans have been stricken with AIDS and more than 100,000 have died since the epidemic began in 1981, according to the federal Centers for Disease Control. And, an estimated 1 million Americans are infected with the AIDS virus.
In a departure from standard policy, the FDA approved DDI even though a series of National Institutes of Health-sponsored clinical trials -- one ongoing at Hopkins -- will not be completed until sometime next year. These trials, which compare DDI to AZT, will fully establish the effectiveness of DDI and assess the impact of its dangerous side effects that some patients already have experienced.
In another policy change, the FDA's approval of DDI was simultaneous for children and adults with AIDS in contrast to AZT, which was withheld from pediatric patients for several years after it had been made available to adults.
"The FDA has broken precedent with the drug in approving it on the basis of what many people feel is extremely scanty data -- data that may in fact not hold up to scrutiny when the results of these trials are really in," said Feinberg, who is co-director of the AIDS Clinical Trials Unit at Hopkins.
"And, I think the FDA has clearly done this out of extreme political pressure, so I cannot say to you, 'Yes, the FDA has a sound basis for approval.' But, I don't believe it."
Feinberg said DDI is not particularly safe, that it has "some serious, serious side effects." Mainly, these are peripheral neuropathy which causes pain and loss of sensation in the feet and hands of some patients and pancreatitis, or inflammation of the pancreas, "which in some cases has been fatal."
She described DDI as "a desperate drug to be used in a desperate situation." She said she would "pick and choose very carefully" the patients she would prescribe it for, adding, "and when people inevitably, despite their AZT, begin to get very sick, I'm not sure that any drug is going to make a difference at that point."
Over the past two years, more than 22,000 Americans with AIDS have gotten DDI at no cost under a special, expanded access program financed by Bristol-Myers Squibb Co., the pharmaceutical firm that developed the drug and will market it.
Under this program, DDI has been available to patients willing to take an experimental drug, to sign a consent form and to undergo more testing than they would if they were using a licensed drug, Cohn said.
"Patients know exactly what they are taking and how much, and DDI is not being compared to any other drug in this experiment," said Cohn. "It does provide information on the drug's safety and lots of information about DDI's side effects. But, we still don't know how effective it is."
Cohn said he would be extra cautious in prescribing DDI if he thought the patient might develop peripheral neuropathy or pancreatitis.
The retail price of DDI is expected to be about $2,000 a year for the most common dosage, or about 20 percent lower than AZT. Bristol-Myers said it would continue to supply DDI free to poor patients not covered by Medicaid.