Purported AIDS Drug Got Cool Reception at FDA : ICN to Renew Fight for Ribavirin
Just a few weeks ago, Milan Panic had plenty of reason to quit the race to find an AIDS treatment.
His company, ICN Pharmaceuticals, had its widely publicized anti-viral drug, ribavirin, shot down by the U.S. Food and Drug Administration. FDA Administrator Frank Young said the agency could find “no evidence of (its) effectiveness” against AIDS.
In addition, the FDA and Securities and Exchange Commission launched investigations into ICN’s activities. To top it off, congressional hearings began in Washington on a variety of alleged improprieties at the Costa Mesa drug firm, including illegal sales of ribavirin to physicians.
But Panic, ICN’s volatile founder and chairman, and a man who has never been accused of ducking controversy, decided to press on. A Yugoslav immigrant who pronounces his name Pahn-ish , he is gearing up for another push for ribavirin.
Panic says he is leaning toward petitioning the FDA for permission to launch a second round of tests of ribavirin on patients infected with the AIDS virus. In April, the FDA challenged the validity of ICN’s first tests and denied the company’s request for expanded testing. In addition to possibly working again with the FDA, Panic says, the company expects to test the drug on patients with AIDS symptoms in Canada and the United Kingdom.
“If as strong a person as I quits, then others will too,” he says of ICN’s efforts to win approval for ribavirin as a treatment for early stages of AIDS.
Failed to Win Approval
For Panic, the fight for ribavirin is a test of personal strength and perseverance.
“In all my mature life, I have tried to come up with a medicine to help people,” he says. “I’m being crucified and I can’t believe it. . . . All I can say is, ‘Forgive them, God, for they know not what they do.’ ”
To Panic’s numerous critics, such comments offer more evidence of his emotionalism and desperate need to keep the spotlight on ribavirin, the only drug the company has developed and the key to its hopes since 1972. The company’s revenues primarily come from distributing ribavirin and other private-label medicines internationally.
Touted by the company during the past 15 years as a treatment for maladies ranging from the common cold to aging, ribavirin has failed to win FDA approval for all but one of its proposed uses. In late 1985, the agency cleared it as an aerosol treatment for a rare childhood respiratory infection.
The company’s entry that year into the heated race to treat AIDS patients fueled suspicions that ribavirin is, in the words of one congressional investigator, “a drug which seems to have been in search of a disease.”
If ICN resumes its quest for FDA approval of ribavirin, Panic and his unorthodox operating style are sure to get renewed attention. The outspoken 57-year-old already has drawn considerable fire for his optimistic--some say “promotional”--statements about the drug’s powers.
Last January, the company upset the FDA and members of the medical establishment--it wasn’t the first time--when Panic announced in a Washington news conference that recent tests showed that ribavirin delayed the development of AIDS in patients showing early signs of the deadly disease. Three months later, the FDA disputed the claim and put further testing of the drug on “clinical hold,” an investigational limbo.
ICN’s management “has not been realistic” in assessing its product, says Sarah Gordon, who follows the medical industry for the Hambrecht & Quist securities firm in San Francisco. “The other drug companies with potential AIDS drugs haven’t conducted themselves this way.”
Even ICN’s supporters say that Panic’s outbursts and courting of media attention have, at best, tarnished the company’s image on Wall Street and within the industry. At worst, they say, the company’s relationship with the FDA has been destroyed.
“The company has a tendency to shoot itself in the foot,” says Craig Dickson, an analyst with Interstate Securities in Charlotte, N.C., and a longtime believer in ribavirin.
ICN’s stock tripled in price to a peak of $34 in August, 1986, before beginning a retreat that brought it to a close of $11.75 on Friday. ICN officials say the SEC is investigating possible insider stock manipulation, insider trading and other matters; the SEC, as a matter of policy, will not comment on current investigations.
Despite the controversy that has swirled around Panic, ribavirin is getting serious consideration from some medical experts in the fight against AIDS.
Samuel Broder, head of clinical oncology for the National Cancer Institute and a leading AIDS researcher, said he believes that the drug “merits further study.” Studies with the drug, separate from any sponsored by the company, are under way or planned at several research centers.
But the problem, says one researcher, is the company’s promotional approach to these studies if the results initially appear promising. “It doesn’t do the company any good to declare the drug good or bad,” he says. “It’s a medical issue, pure and simple.”
An FDA insider says the company’s principal problem is its lack of experience in developing new drugs and guiding them through the federal government’s detailed review process. Noting that ribavirin is the company’s first proprietary drug, the official says ICN is not well versed in designing clinical studies, gathering the necessary data and putting them in the form that the FDA expects.
“We’re trying to be helpful,” the source says. “But remember, this is a single product company. . . . They’ve vested a lot in this single product and it’s hard for them to deal with the product approval process.”
Started on Shoestring
Panic, who immigrated to the United States in 1956 and started ICN in 1960 with just $200, has taken his case to the public. Likening himself to Chrysler Corp. Chairman Lee Iacocca, Panic says he’s a proud promoter of his drug because he believes in it and believes it is being denied a fair evaluation in the United States.
Panic, who says he takes ribavirin every time he has a cold or the flu, considers himself a small entrepreneur at the mercy of the FDA, which he portrays as a weighty, insensitive government bureaucracy. He refers to the agency’s top official, Young, as “the jerk commissioner.”
In his eyes, ICN, which made a profit of $13 million last year on sales of $103 million, is being forced to compete head-on with the U.S. government.
Panic complains that the FDA has given preferential treatment to two compounds developed by the National Institutes of Health, a sister agency. One of the two medicines, azidothymidine or AZT, was licensed to Burroughs Welcome, a British drug maker, and has received FDA approval for AIDS treatment. The other, dideoxycytadine or DDC, has been licensed to Swiss drug giant Hoffman LaRoche and is undergoing limited testing.
Panic argues that the FDA has required ribavirin to meet a higher standard of proof than the other compounds, a charge that the FDA’s Young vigorously disputes.
When the FDA denied ICN’s request to expand evaluation of ribavirin on patients suffering from the pre-AIDS condition of lymphadenopathy syndrome, or LAS, it questioned how the 163 patients selected for the test were assigned to treatment groups. Specifically, the FDA wondered if patients at a higher risk of developing AIDS were assigned to receive the placebo, which would improve the showing of the drug’s effectiveness.
According to researchers conducting the tests, none of the 52 patients receiving the maximum allowable dose of ribavirin developed AIDS during the seven-month study, while six of the 55 patients receiving a lower dose of the drug and 10 of the 56 patients receiving the placebo contracted the disease.
Severe Symptoms
But the FDA says it discovered that the four medical research centers administering the tests admitted 16 patients whose pre-AIDS symptoms were so severe that they should have been disqualified. Of those 16, at least six were assigned to receive placebos and those six all contracted AIDS.
In addition, in testimony before a special congressional oversight committee, FDA officials said that six of another seven patients with particularly advanced symptoms were assigned to a group receiving placebos.
After removing the questionable patients from its evaluation, the FDA concluded that the drug’s results were no better than the placebo’s.
Panic, however, notes that the same researchers who tested ribavirin also tested AZT. Thus, he argues, if the researchers failed to evaluate one drug properly, they must have done the same with the other, but AZT was approved for treatment before the tests were completed anyway.
“You can’t make the researchers look like crooks on one thing and not on the other,” Panic says. “I can’t understand why the level of confidence is lower for the ribavirin study than for the AZT study.”
Young, denying that AZT received preferential treatment, says the agency can’t explain the apparent differences between the way the tests on the drugs were conducted.
But to Panic, the denial was a case of “the big squashing the small.”
“All great discoveries get hit like this,” he says. “Do you think Thomas Edison had an easy time convincing people to use electricity? I feel I’m trying to help the human race and I’m being hit. It’s just like St. Paul. They threw stones at him and they throw stones at me. Now they are throwing dirty stones at me.”
