The real Elan tragedy
'My first reaction was panic,' said MS sufferer Wendy Sargent, who was participating in a Tysabri trial. The drug's withdrawal has raised question marks over the future of both the company and those who need it
6 March, 2005, The Sunday Tribune
TYSABRI changed Wendy Sargent's life.
Before the 30-year-old Toronto native was diagnosed with Multiple Sclerosis in October 2001, she was missing weeks from work, feeling run down and her eyesight was being periodically impaired by optic neuritis, an inflammation of the optic nerve.
"There had been speculation it might have been a brain tumour that was causing my attacks, " she told the Sunday Tribune last week. "I had problems with my vision and had severe vertigo. I also had Lhermitte's sign, which is a tingling sensation down your spine every time you move your chin to your chest. You get a shocking sensation. But it was the vertigo that was the real clincher. I couldn't function. I was walking like a drunk," laughed Sargent, who works as a risk assessment administration assistant in the Canadian city.
Potential wonder drug Tysabri offered hope for multiple sclerosis sufferers and Elan shareholders alike. Its withdrawal last week wiped 6bn off the firm's value and dashed the hopes of both patients and investors.
"I had an MRI scan and was diagnosed with Multiple Sclerosis, and then went to see a neurologist who was one of the doctors heading the Tysabri phase III trials in the city," Sargent explained.
"He was looking for individuals to take part in the study, and he didn't really try to sell me on it. He presented me with my options, but just said there had been promising results in phase I and phase II."
It didn't take her long to make up her mind. "You had drug A or B that might cost C$20,000 (E12,250) a year, or a study that was free. Which do you choose?"
But her decision was influenced by more than just getting free Tysabri, which was jointly developed by Elan and Biogen-Idec and was withdrawn last week following the death of a patient from a rare central nervous system disorder called progressive multifocal leukoencephalopath (PML). A second case was confirmed on Thursday evening.
The two patients had been taking a combination of Biogen-Idec's Avonex MS treatment and Tysabri. Used as a stand-alone treatment, Tysabri had been shown to slow the progression of the symptoms of MS by 42% compared to a placebo.
"My biggest draw for going into the study was the fact I knew I would be so well taken care of. Being a study participant means that they're just doing checks all the time," explained Sargent.
She took her first infusion in early 2002 and within the the first month she felt a difference.
"It's hard to explain it. I had more energy. I had more clarity of thought. The vertigo and other symptoms regressed and I haven't had any remissions since I started taking Tysabri," she said.
But for Sargent and many other MS sufferers, one of the first truly effective treatments for the condition is now unavailable, leaving them in limbo, unsure how withdrawal from the drug will affect them, and hoping Tysabri will be declared safe and back on the shelves before the end of the year.
Many have expressed their disappointment to the Sunday Tribune, and they won't know the outcome of further studies for months. Others, from states including Florida and Indiana, have said that either they or relatives who recently began taking Tysabri in conjunction with Avonex have seen their condition disimprove.
In the meantime, Elan, the biotech firm that had just sorted out a financial mess that almost saw it collapse, has seen its own fortunes rapidly decline, its share price plummeting almost 70% in one day in Dublin from E20.30 to E6.49. It has since dropped below E5.
It is a depressing scenario for both patients and investors.
"This is a serious blow," said analyst Ian Hunter of Goodbody Stockbrokers.
"The question that has to be answered now is whether Tysabri will come back. We're fairly confident it will but it may not have the same status as it did. The best-case scenario is that the PML was caused by something completely unrelated to Tysabri, which may be unlikely. The other end of the spectrum is that they find something that is directly related and the whole drug has to be pulled."
That would be an unmitigated disaster for Elan and would severely test investor faith in the firm. It had been hoped that Tysabri would help Elan return to profitability next year, and that ultimately it would generate up to $3bn in revenue a year at its peak. Now, all that hangs in the balance.
Elan may be safe for the time being - it has $1.5bn in cash to keep it going - but fundamental issues will need to be quickly resolved.
The patient who died from PML was initially misdiagnosed, and had been taking a number of other drugs along with Tysabri and Avonex, so it is likely to be difficult to establish the direct cause of PML. It has been known for well over a decade that drugs such as Tysabri, which suppress the immune system (in MS, white blood cells that normally fight infection instead attack healthy brain cells), could cause problems.
Tysabri's future is directly linked to Athlone-based Elan, but the drug has its roots far from the banks of the Shannon. In 1992, San Francisco-based Athena Neurosciences (which Elan acquired in 1996 for $635m in stock) first released results from experiments in which rats suffering from an ailment similar to MS were given an antibody to prevent brain inflammation and paralysis.
At the time, it was hoped this research would lead to a treatment for MS, but the highly regarded science magazine Nature, in which the research was published, warned in an editorial that the risks for patients were obvious.
"Patients given properly immunosuppressive doses may acquire dangerous intercurrent infections and handle them less effectively," it said.
Alexander Rae-Grant, a senior doctor and influential director of the Multiple Sclerosis centre at Lehigh Valley Hospital in Pennsylvania, describes the PML infection issue as a "disaster".
"The combination [of Tysabri and Avonex] may have done too good a job of suppressing the immune system. That's what we're trying to do, but you get other things going on," he explained.
Although "dismayed" at the decision to pull Tysabri, he is still hoping it will be brought back to market.
Roughly 40 people of the 1,200 who attend his clinic had already started the oncea-month Tysabri infusion, while another 18 had taken part in previous trials for the treatment at the hospital.
"We and many other people felt that this was a significant breakthrough, " he told the Sunday Tribune. "I thought it would be similar to the previous medications, but on every measure that we could see it was superior to others by a significant margin. We were really looking forward to it as a major breakthrough. It's not that the other medicines don't help, they just clearly don't do everything we want them to do."
One of the other big battles facing Elan now is a public relations one. Even if Tysabri is found to be safe as a monotherapy, it is highly likely that it will have lost its wonder drug status. There was anecdotal evidence that, until last week, Elan could hardly keep up with demand for Tysabri and MS patients were demanding the treatment from their physicians. It seems likely that that will all change if Tysabri makes a comeback, with the drug losing its allure for some MS sufferers. That will push profitability back even further and significantly broaden the period over which income from the treatment is generated, diminishing its attraction as an investment.
"I think it will definitely change the conversation," said Rae-Grant. "The likelihood is that it will be for people with very much more active MS for whom the potential downside is less than the downside of not doing something different. It's going to be more of a conversation than it was initially."
But for those who have seen the changes, Tysabri's withdrawal is a frightening prospect.
"My first reaction was panic," said Wendy Sargent, on hearing the news last week. "I feel, whether it's a physical or mental dependency, that this drug is keeping me on my feet. We don't know yet if there are withdrawal symptoms and what they might be. I get the infusion every four weeks, and in the third week I feel a physical decline."
She was due her next infusion last Friday. "It's a big mystery as to how I'm going to react to the sudden absence of this medication, " she said.
The impact of its potential absence from Elan's drug portfolio, however, is no mystery for investors.
(c) Tribune Newspapers PLC - Business, pg 5
ANALYSTS ADVISE A CAUTIOUS APPROACH TO DRUG'S RETURN
ANALYSTS are hopeful that Tysabri will eventually return to the market, but in the meantime are warning investors to be cautious.
Ian Hunter of Goodbody Stockbrokers believes there is as much chance that Tysabri will be found to be faultless in the death of the patient from PML as there is of the drug being found to be the cause. Then there's middle ground - which seems more likely - that will allow Tysabri to be used as a stand-alone treatment without being combined with other drugs such as Biogen-Idec's Avonex.
Elan said a "realistic" timeline for the reintroduction of Tysabri could be late summer or early autumn, but that may be optimistic and it could be next year before it reappears.
Tysabri, made from genetically engineered mouse cells taken from a cell cancer called myeloma, isn't just a potential MS treatment. It is hoped it will also benefit people suffering from rheumatoid arthritis and Crohn's disease, an alimentary tract disorder that causes chronic pain and in"ammation. But most of Elan's revenue from Tysabri would have been generated from MS patients.
Also in the Elan product pipeline is Prialt, a severe pain relief drug that was approved in the US at the end of December. Elan acquired Prialt when it bought California-based Neurex in 1998 for $741m.
Prialt, which is administered directly to the spine, is the synthetic equivalent of a naturally occurring conopeptide (a compound of amino acid molecules) found in a marine snail known as Conus magus. A non-opioid drug, it can be used by patients who are not able to receive morphine, for example. A novel treatment, its sales are still expected to be significantly less than Tysabri, with Elan expecting peak Prialt revenues of $150m to $250m a year.
The company's pipeline has been diminished by its sale of drugs and subsidiaries to pay down debt, leaving the company focused on drugs for autoimmune and neurodegenerative diseases.
Among the drugs it sold were Zonegran, an epilepsy treatment; Skelaxin, a muscle relaxant; and Sonata, used for insomnia.
Elan is also developing an Alzheimer's vaccine in conjunction with pharmaceutical giant Wyeth.
Last year the two firms received a number of patents in relation to the treatment. In 2002 trials of Elan's first Alzheimer's drug were abruptly halted when it was found that it caused dangerous brain swelling in some patients. Elan is also researching Parkinson's disease.
(c) Tribune Newspapers PLC, Business, pg5