Novartis AG’s Gilenya multiple sclerosis pill lost market share for the first time in January, following the deaths of some patients soon after taking the first pill available for the disease in the U.S.
Gilenya’s share of the U.S. market for so-called immunomodulatory drugs against MS fell to 6.1 percent from 6.2 percent in December, according to data from Wolters Kluwer NV, a market research company. The decline was the first after 15 months of growth, at a median of 15 percent a month, since the treatment received U.S. regulatory approval in September 2010.
The Food and Drug Administration and the European Medicines Agency are investigating 11 deaths among Gilenya patients. In the past month, analysts have cut their forecasts for peak sales of Gilenya by 10 percent to $2.1 billion in 2016, according to the average of six estimates compiled by Bloomberg.
The deaths have “made me a little more cautious,” said Aaron Miller, chief medical officer of the U.S. National Multiple Sclerosis Society, and a medical director at Mount Sinai Hospital in New York. “I am not somebody who has recommended Gilenya as a first-line drug prior to these reports, and I’m still not recommending it as a first-line drug until we get more data.”
Miller has about 800 patients under his care and has put about 30 on Gilenya since it was approved, he said. He prefers injectable drugs, which include products such as Teva Pharmaceutical Industries Ltd.’s Copaxone and Biogen Idec Inc.’s Tysabri as first-line treatments.
There have been a record number of new prescriptions in the U.S. in the past few weeks, Basel, Switzerland-based Novartis said in an e-mailed statement. The rate of growth may slow and then accelerate again, the company said.
“Some uncertainty is to be expected in the marketplace as some physicians and patients wait for final review and potential label changes,” Novartis said. “Overall, we see Gilenya continuing to grow in volume. Gilenya potential is seen as unchanged.”
The trend in analysts’ sales estimates for Gilenya is “exactly a reflection of the safety concerns,” Martin Voegtli, an analyst at Kepler Capital Markets SA in Zurich, said in an e-mail. On Feb. 24, Voegtli cut his forecasts by 12 percent to $1.96 billion in 2016 and by 11 percent to $2.1 billion in 2017.
“We still expect Gilenya to remain on the market and return to growth once the reviews have been completed,” he said.
Novartis said Dec. 12 that a U.S. patient had died within 24 hours of starting treatment with Gilenya, triggering reviews by the FDA and EMA, which reported a further 10 deaths among patients taking the medicine. Six of those deaths were unexplained, three patients died of heart attacks and one due to disruption of heart rhythm, the EMA said Jan. 20.
“A role for Gilenya can neither be confirmed nor excluded at this time,” Novartis said of the U.S. death.
The EMA’s Committee for Medicinal Products for Human Use has said it expects to complete its review by its March meeting, which is scheduled for next week.
Worldwide sales of MS immunomodulatory medicines exceeded $11 billion in 2010. The U.S. market was about $5.2 billion, according to Wolters Kluwer data, though that doesn’t account for rebates and discounts and may not include all U.S. sales. Weekly prescriptions for Gilenya have declined 1.5 percent since reaching a peak in December, according to the four-week average of Wolters Kluwer data analyzed by Bloomberg Industries.
Timothy Vollmer, professor and director of clinical research in neurology at the University of Colorado in Denver, said he has stopped using Gilenya in patients who had been taking older treatments.
“If they have any history of any kind of cardiac disease, we won’t consider the drug,” Vollmer said in a telephone interview. “For older patients, we’re a little bit reluctant because of the cardiac issues.”
About 10 percent of patients have been taken off Gilenya after a careful review of safety information, Vollmer said. His clinic has about 2,000 patients, including 800 on Tysabri and 150 on Gilenya. Novartis has told Vollmer the clinic is one of the biggest Gilenya prescribers in the U.S., he said. Vollmer said he hasn’t seen any of his patients experience Gilenya-related heart issues.
“We actually felt substantially let down by the company, because they knew about those things and they weren’t telling us about it,” Vollmer said in a telephone interview. “For us to use it the way we were using it we needed to feel that they were going to be quite forthcoming with all the safety information.”
MS causes the immune system to attack the insulating tissue around nerve fibers. This stops nerve cells from sending signals, sapping patients’ energy, blurring their vision and slowly robbing them of mobility, balance and coordination.
Treatments are designed to rein in the immune system, which can lead to side effects. Gilenya, the first MS pill to reach the market, 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.
It isn’t clear whether the drug contributed to the deaths that regulators are reviewing, and the rate of fatalities is in line with the expected rate based on the 30,000 patients who have been treated so far, Novartis said in January.
Tysabri, sold by Biogen and Elan Corp., also faced safety questions after being approved by the FDA in 2004. The injectable therapy was suspended in 2005 after some patients developed progressive multifocal leukoencephalopathy, or PML, a viral infection in the brain that usually leads to death or severe disability.
Tysabri returned to the market in 2006 with a risk-management program for patients who didn’t benefit from rival medicines. The FDA in January approved a revised label for Tysabri that warns that patients who have antibodies against the so-called JC virus are more susceptible to developing PML. The European Commission approved the same change in June. Biogen also developed a test for the antibodies.
Gilenya’s potential link to heart problems came as a surprise, said J. William Lindsey, an associate professor of neurology at the University of Texas Medical School at Houston who has put about 20 of his 500 patients on Gilenya so far.
Information on the 11 deaths provided by Novartis didn’t give any clues as to a “unifying factor” that would link the cases, Lindsey said in a telephone interview.
“If they can look at those and say, ‘All these people had this in common, and we can prevent this if we don’t give it to these people,’ that would be very helpful,” he said. “Right now you sort of cross your fingers and hope it doesn’t happen to that particular patient.”
Lindsey said he hasn’t changed his approach to prescribing the drug, and started two patients on it the week before he spoke to Bloomberg News.
“I discussed the cardiac things with them, and let them know, and both of them felt that MS was causing them enough problems that a 1 in 3,000 risk was something they were willing to accept,” he said.
The drug may soon face competition from Biogen Idec Inc., the world’s biggest maker of treatments for MS. The Weston, Massachusetts-based drugmaker applied last month for U.S. marketing approval for BG-12, an experimental pill against the disease that reduced the annual rate of relapse by as much as 51 percent compared with placebo. Teva’s Copaxone reduced the rate by 29 percent.
“BG-12 is a real threat,” said Tim Race, an analyst at Deutsche Bank AG in London who rates Novartis a “buy,” in an interview. “From the data we’ve seen, efficacy is comparable to Gilenya and the safety seems slightly better, which suggests that it’s going to be the market leader.”