West Coast Editor
Having found no new cases of progressive multifocal leukoencephalopathy in a completed safety review of Tysabri patients, Biogen Idec Inc. and Elan Corp. plc said they hope to get the multiple sclerosis drug back on the market, with regulatory paperwork to be filed in the fall.
Wall Street seemed to like it. Biogen Idec's stock (NASDAQ:BIIB) closed Tuesday at $41.24, up $2.82. Dublin, Ireland-based Elan's shares (NYSE:ELN) ended the day at $9.09, up $1.09, or 13.6 percent.
Somewhat less sanguine was Solomon Margolin, a well-known MS and drug researcher. President of Dallas-based Marnac Inc., he co-discovered and developed prednisone and prednisolone, as well as the active ingredients in such widely used drugs as Dimetapp, Contac and Coricidin.
"I've taken 24 drugs into the market with the FDA, and we're very happy that we've never hurt anybody," he said, adding that he is "not in the business of being negative about [other companies], but trouble is trouble, and to pretend it doesn't exist is not acceptable. That's what we're faced with now."
Biogen Idec and Elan voluntarily pulled Tysabri from the market this spring after the link to PML was discovered. Three cases have been confirmed, two of which were fatal, with a potential fourth case reported in June. (See BioWorld Today, March 1, 2005.)
In the safety evaluation, more than 2,000 MS patients from clinical trials were eligible and 91 percent of those participated. Of those, 99 percent visited their treating physician and had a neurological exam, and 98 percent underwent an MRI exam. Also included in the review were any reports of potential PML in patients given Tysabri in the commercial setting.
The ongoing safety evaluation of Tysabri in Crohn's disease and rheumatoid arthritis is expected to finish by the end of summer, and the company said it is taking "preliminary steps" to restart further trials in MS.
Margolin said Tysabri should be shelved permanently.
"I wouldn't prescribe it," he said. Though he is not in medical practice, his wife is a physician and maintains an office in Dallas and "she wouldn't prescribe it, either," he said.
"I feel sorry for [Biogen Idec and Elan executives], but patients are more important," Margolin said.
Scientists likely had patients in mind when they came up with Tysabri (natalizumab), the alpha-4 antagonist formerly known as Antegren, approved late last year and hailed as an eventual blockbuster. (See BioWorld Today, Nov. 29, 2005.)
Accelerated market clearance was based on single-year results from the monotherapy trial known as AFFIRM and the SENTINEL study, which combined Tysabri with Biogen Idec's MS drug Avonex (interferon beta-1a). In AFFIRM, Tysabri reduced relapse rates by 66 percent compared to placebo, and top-line results from SENTINEL made public in conjunction with the approval indicated a 54 percent reduction in relapse rate for Tysabri plus Avonex vs. Avonex alone.
Impressive, but then came PML - which is enough to stop the push for Tysabri, or should be, said Margolin, whose firm also is active in MS. Phase II data with Marnac's oral compound pirfenidone for secondary progressive MS were reported in the April edition of Multiple Sclerosis Journal. The drug's active ingredient is a small chemical molecule, 5-methyl-1-phenyl-2-(1H)-pyridone (CAS 53179-13-8), which blocks receptors for tumor necrosis factor-alpha.
Pirfenidone has other potential uses. Intermune Inc., of Brisbane, Calif., licensed the drug for idiopathic pulmonary fibrosis and plans to move it into Phase III in the first half of next year.
Regarding Biogen Idec, Elan and Tysabri, analyst Christopher Raymond of Robert Baird & Co. in Chicago wrote in a research note Tuesday that the safety data will lay to rest the rumors about more PML cases, but "even in the best-case scenario - a near-term Tysabri re-launch - we still see a limited commercial opportunity for Tysabri, given its safety profile." Raymond stayed neutral on Biogen Idec, of Cambridge, Mass.
Margolin, for his part, nodded at the uptick in Biogen Idec and Elan shares Tuesday, based on the safety findings.
"I'm a fond believer in Wall Street; it has its role," he said. "But people get enchanted by money." Margolin, inventor of more than 40 U.S. and foreign patents pertaining to pharmaceutical agents, said he values more the experience of "striking it right with people and seeing somebody who is paralyzed get up out of the chair."
No doubt, Biogen Idec and Elan would like to see more Tysabri patients do just that, but Margolin called the PML risk too great. The firms "have plenty of other things they can work on," he said.
Investors will press their demands, Margolin acknowledged.
"I know all about that business too, and I don't welcome it and never have," he said. "People are not as much concerned about patients as they should be."
At 86, he might be a voice to be shouted down by market demands, "but I'm not disappearing yet," Margolin said. "I've had cancer three times, and thanks to good medical care and good drugs, I'm still here."