Novartis Drug Heralds Multiple Sclerosis Advances

The first in a new wave of multiple sclerosis medicines, from drugmakers led by Novartis AG and Merck KGaA, may reach the market next year, making therapy more convenient for patients and boosting profits.

In Seattle this week, the drugmakers will present results from human trials of two oral drugs. If the products win U.S. approval, patients for the first time will be able to take pills, rather than shots or transfusions, to slow the nerve- damaging condition. Five more pills and two infusion therapies may join the $7.5 billion a year MS market by 2014, according to the National Multiple Sclerosis Society in New York.

Progress against MS is coming on three fronts, said John Richert, a doctor who leads research at the society. The new drugs may reduce the frequent relapses most patients face. Improved detection may allow earlier treatment before symptoms emerge. Stem-cell therapies now being tested may go even further, reversing disability in patients with advanced disease.
“In terms of stopping disease activity, there are more therapies coming onstream than ever before and many of these also appear to be more potent,” Richert said in a telephone interview. “While the whole idea of repairing the nervous system really seemed like science fiction five to six years ago, advances in the last year suggest this may well be within our grasp.”
Novartis was unchanged at 42.46 Swiss francs in Zurich trading. Merck KHaA, which today reported a decline in first- quarter profit and said “the bottom” had been reached, advanced 1.2 euros, or 1.8 percent, to $67.70 euros in Frankfurt trading.

Rogue Cells

First described 140 years ago, multiple sclerosis causes the body to attack itself through the immune system. Rogue immune cells travel to the brain and spinal cord and enter the nervous system. There the cells assault and destroy myelin, the fatty substance that surrounds nerve-cell fibers. That interferes with the nerve cells’ ability to transmit electrical impulses and move muscles.

MS generally starts in early adulthood, disrupting people’s coordination and balance and sometimes leading to damaged vision and paralysis. For Rhonda McHenry, a fall in 1994 while chasing her then 9-month-old son, and the resulting nerve pain, led to an MS diagnosis.
McHenry, now 44, was diagnosed with the “relapsing- remitting” form of MS that makes symptoms flare and recede and that 85 percent of patients have initially, according to the MS Society.

Drugs Against Relapse

In one way, she was fortunate. Around the time of her diagnosis, three new drugs were approved to prevent MS relapses. They included two made from proteins called beta interferons -- Avonex, made by Biogen Idec Inc. of Cambridge, Massachusetts, and Betaferon, made by Bayer AG of Levrkusen, Germany. The third treatment is Copaxone, made by Teva Pharmaceutical Industries Ltd., of Petah Tikva, Israel, from a synthetic protein.

The treatments included Avonex, made by Biogen Idec Inc. of Cambridge, Massachusetts; Betaferon, made by Bayer AG of Levrkusen, Germany; and Copaxone, a product from Teva Pharmaceutical Industries Ltd., of Petah Tikva, Israel.

These products, along with Rebif, made by Merck KGaA, of Darmstadt, Germany, inhibit the overactive immune response found in MS, reducing damage to nerves and slowing disability, Richert said. Rebif was approved by the U.S. Food and Drug Administration in 2002.
The four, known by their initials as the ABCR drugs, now dominate the MS marketplace, with more than $1 billion each in sales annually. Biogen’s Avonex led the pack with $2.2 billion last year. Geoffrey Porges, an analyst with Sanford C. Bernstein & Co. in New York, projected in a report last year that the MS market will grow to $10.8 billion in 2013.

Blocking Cell Movement

As researchers have learned more about how the immune system attacks nerves, they have been able to design drugs that interfere with that process, Richert said.

The newest MS treatment on the market, Biogen’s Tysabri, blocks the movement of immune cells from the bloodstream into the nervous system.

The experimental Novartis drug FTY720 disrupts the movement of immune cells at an earlier stage than Tysabri, keeping them from leaving lymph nodes and entering the bloodstream, according to Richert.

German Merck is attempting to turn a cancer drug, cladribine, into an MS medicine because it suppresses the immune system, blunting its attack on nerve cells. The product was approved to treat leukemia more than a decade ago.

Results Next Week

Novartis, based in Basel, Switzerland, and Merck will release results this week at a Seattle meeting of the American Academy of Neurology, a professional association based in St. Paul, Minnesota. Preliminary findings already released by both companies suggest that the drugs limit relapses.

The data on side effects may determine if and when the products will take revenue from the Bayer, Biogen and Teva products, said Jack Scannell, a London-based analyst with Bernstein.
Merck plans to submit its FDA application in June or July, said Bruno Musch, the company’s head of global clinical development for neurodegenerative diseases. Novartis intends to make its submission by the end of the year, said Joseph Jimenez, head of the pharmaceutical division, in a conference call last week.

MS Pills Advance

Other companies are also racing to bring MS pills to market. Acorda Therapeutics Inc., based in Hawthorne, New York, said on April 23 it had reformatted and resubmitted an application for a pill called Fampridine-SR. The drug improved the walking speed of MS patients in a study, according to the company.

Biogen, the leading maker of MS therapies; Teva; and Sanofi-Aventis SA, of Paris are conducting late-stage trials of their own MS pills. An injectable drug called Campath, being developed by Cambridge, Massachusetts-based Genzyme Inc. and Bayer, may be the most effective therapy for people with severe MS, according to Porges. He projects Campath revenue will top $1 billion by 2013.

Data on side effects of all the new therapies will be closely watched because drugs that disrupt immune system activity can increase the risk of infections, Richert said.

Tysabri was pulled from the market in 2005 after three patients developed a life-threatening brain illness and two of them died. The FDA allowed Tysabri sales to resume in July 2006 after deciding its effectiveness outweighed the risk. The company has since reported six new cases, with one death.

Side Effects

If the new pills cause side effects, that may negate their advantages, said Al Sandrock, senior vice president of neurology for Biogen, whose drug BG-12, also taken by mouth, is in late- stage testing.

“The safety profile is never fully appreciated until a drug has been in thousands of patients for many years -- we certainly learned that,” Sandrock said.

Elizabeth Morrison, a neurologist at the Cascadia Multiple Sclerosis Center, a medical practice in Bellingham, Washington, has MS herself. She said she will probably keep taking Copaxone, as it controls her symptoms without causing side effects such as chest pain or anxiety, which patients can experience.

She also said she won’t rush to prescribe the new drugs for other patients.
“I think people with MS may think, ‘Oh, an oral medication -- that will be safer or easier for me,’” she said in a telephone interview. “But that’s not necessarily the case.”

Doctors will be cautious in prescribing the new pills until their safety is clear, said Bernstein’s Scannell.

Convenience vs. Risk

“The fact that they’re convenient and oral doesn’t trump the fact that they might give you a horrible brain infection or cancer,” he said in a telephone interview.

In addition to having more and better drugs, clinicians can now find MS lesions using MRI scans earlier than ever before, said Peter Wade, medical director for neurology at the Mandell Center for Multiple Sclerosis, at Mount Sinai Rehabilitation Hospital in Hartford, Connecticut.
“Now there is an urgency to diagnose the disease as quickly as possible because the medications we have currently available work much more effectively early on,” Wade said in a telephone interview.

For patients with advanced disease, early detection is no longer relevant.

For most of the past 15 years, daily injections of Copaxone have controlled Rhonda McHenry’s relapses and when they didn’t, five days of intravenous steroids usually cut them short.
Today, the relapses come more often, last longer and cause more weakness, making walking more difficult for McHenry, who is today the chief operating officer for a Kansas City bank. Now she hopes she will be lucky again and benefit from new therapies.

Clinical Trial

She qualified for a clinical trial that will use patients’ own stem cells to reset their immune systems. Patients will have their blood-forming stem cells extracted before chemotherapy drugs kill the immune cells in their bone marrow. The stem cells will then be returned to rebuild their marrow, creating a fresh batch of immune cells.

The immunologist leading the study, Richard Burt of Northwestern University’s Feinberg School of Medicine in Chicago, reported in January that the procedure reduced disability in 21 patients in a pilot trial. He and his colleagues aim to show by the end of 2012 that the therapy can roll back symptoms in a 110-patient trial.

McHenry, who is scheduled to start the stem-cell treatment in July, said she hopes it will halt the worsening of her disease before it causes more-severe disability.

“If it were to stop the progression, even for five years, that gives me five more years to live life and enjoy it,” she said. “If not, I hope they learn from me what it’s going to take to make it work for someone else.”