Novartis explores the potential of Gilenya® against primary progressive MS
GilenyaFive years ago, Jason DaSilva, a film maker with multiple sclerosis, was able to roam his New York neighborhood, bar hopping or visiting coffee shops. Today, he needs a walker to manage 10 feet because the degenerative nerve disorder has worsened and there’s nothing to treat his severe form of the disease.
Novartis AG is working on a pill to change that. The drugmaker won approval in September to sell the first oral medicine in the U.S. to treat the commonest form of MS, Relapsing - Remitting MS and the European Union’s drug regulator may follow suit as soon as next month. The company is beginning to test the pill, Gilenya, against the steadily worsening form of the disease that afflicts DaSilva.
“There is still a big need, an urgent need,” said Alan Thompson, a neurologist at University College London. “An oral agent would be a big deal.”
Gilenya already may be on its way to becoming Basel, Switzerland-based Novartis’s biggest product, with analysts on average predicting $1.8 billion of annual revenue by 2014. Sales may surge to $5.4 billion a year by 2016 as the drug’s use is expanded to advanced MS, UBS AG says. Gilenya is the most expensive MS drug, costing about $48,000 annually.
Success would help Chief Executive Officer Joseph Jimenez overcome the loss of Novartis’s current top seller, Diovan, which had sales of $6 billion last year. The hypertension drug starts to lose U.S. patent protection in 2012.
Multiple sclerosis causes the immune system to attack the insulating tissue around nerve fibers, called myelin, leading to scars and inflammation. This stops nerve cells from sending signals, leading to symptoms such as blurred vision and muscle weakness. Injected drugs including Teva Pharmaceutical Industries Ltd.’s Copaxone and Biogen Idec Inc.’s Avonex treat a common form of MS in which symptoms come and go. The more debilitating form that can rob sufferers of the ability to walk has defied therapy.
Experiments with rats and brain scans of humans taking Gilenya led Novartis to believe the drug that may be effective against the more severe form of the disease, known as primary- progressive multiple sclerosis, said Trevor Mundel, Novartis’s head of development. The company is looking for volunteers to test the drug in 86 centres in North America and Europe, according to the Web site clinicaltrials.gov.
“If they can show that it works, then this is a home run,” Karl-Heinz Koch, an analyst at Helvea SA in Zurich, said in an interview. “This is the holy grail.” He recommends buying the shares and predicts they may gain 28 percent in the next year.
Gilenya blocks white blood cells called lymphocytes from circulating in the body, preventing them from reaching and doing damage to the brain, spinal cord and optical nerves. Not only did the drug protect a certain type of nerve cell in rat and test tube experiments, scans of patients taking the drug showed a slowing of brain shrinkage, a sign that the treatment may lessen the destruction of nerves.
This may mean that in addition to calming the immune system, Gilenya may also curb inflammation, offering two possible ways to take on the disease, Mundel said.
Primary-progressive MS seems to be marked by a lower level of inflammation that is more damaging to nerve cells, said Thompson, who also is editor in chief of the journal Multiple Sclerosis. Patients may not benefit from available therapies, so-called immunomodulators, because they primarily target inflammation, Thompson, the UCL researcher, said.
The trial of the drug in primary-progressive multiple sclerosis also may encourage doctors to prescribe Gilenya for patients with the milder form as well, because it would show that the drug both repairs nerves and calms the immune system, Thompson said. “If you had a treatment that combined the two, using it early could have profound effect on the long-term outcome,” Thompson said.
Multiple sclerosis affects about 2.5 million people worldwide, many of whom have trouble sticking with current therapies because they’re difficult to use or have side effects, according to the National Multiple Sclerosis Society, a New York-based patient group. About 10 percent have primary- progressive multiple sclerosis.
“The medicines on the market have been evaluated in clinical trials based on their ability to slow relapses, while people with PPMS don’t have relapses,” Nicholas LaRocca, the society’s vice president of health-care delivery and policy research. “This is a very challenging form of MS.”
Roche Holding AG’s Rituxan, approved for rheumatoid arthritis, non-Hodgkin’s lymphoma and leukemia, failed to slow PPMS in a two-year study, according to results published in 2008. Analysts at Deutsche Bank AG had expected it to earn more than 500 million Swiss francs ($518 million) annually for Roche. Biogen Idec’s Avonex also didn’t make it beyond clinical testing for the advanced form of the disease.
The lack of alternatives has led DaSilva to try Rituxan anyway. “There’s nothing else out there, so I chose something better than nothing,” DaSilva, 32, who lives in New York’s East Village, said in an interview.
History of Disappointment
Merck KGaA also has developed an oral treatment for the more mild form of MS. European regulators in September rejected the drug, cladribine, as being too risky, and the FDA delayed a decision until February. The drug, which is approved for use in Russia, isn’t being tested in the more severe form of the disease, said Gangolf Schrimpf, a spokesman for the Darmstadt, Germany-based company.
“The history of PPMS has been one of disappointment,” Novartis’s Mundel said. “Everything has been thrown at this disease and nothing has worked.”
Still, using Gilenya as a treatment may be a long way off. Because of the slow-moving nature of the disease, the last patients may not finish the trial until 2013, according to clinicaltrials.gov. Even then, there’s no guarantee the drug will prove successful, said Thompson, of University College.
“It’s impossible to say, but I am an optimist,” said Aaron Miller, a neurologist at the Mount Sinai School of Medicine in New York. “The trial is designed in a way to have optimal chances of success.” Miller is an investigator in the PPMS study.
Even for people with the milder form, Novartis expects Gilenya sales to build slowly, as it takes some time for doctors to shepherd patients through the safety tests the U.S. Food and Drug Administration required for the drug.
DaSilva, who is making a film called “When I Walk” about living with the disease and searching for treatment, says he would be willing to try any new drug.
“It would be wonderful to have something we can try,” he said.
Source: Bloomberg ©2010 BLOOMBERG L.P (21/12/10)
Treatment: CCSVI both IJV ballooned 09/2010, No DMDs, Tysabri on hold after 24 Infusions, after LDN, ABX Wheldon Regime for 1 year.