Progress Fighting Parkinson’s Drug Side Effects; “I’m basically going to be incapacitated by the drug that’s helping me, and that’s terrifying,”

March 25, 2013, 6:38 p.m. ET

Progress Fighting Parkinson’s Drug Side Effects

By SHIRLEY S. WANG

As they continue to wait for a cure, patients with Parkinson’s disease may soon see more consistent relief from side effects of the drugs that treat it.

One of the most pressing problems facing patients today is that the most effective treatment available wears off over time and may induce often severe involuntary movements. A number of new treatments are being developed to address the wearing-off effect or attenuate the movement side effects, called dyskinesia, that come with the drug, levodopa.

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In findings presented last week in San Diego at the annual meeting of the American Academy of Neurology, researchers reported significant results from a mid-stage trial of Biotie TherapiesCorp.’s experimental medicine tozadenant. Meanwhile, drug makerAbbVie Inc. reported more in-depth results on its experimental gel made from a combination of existing drugs and delivered using an infusion pump, which dramatically increased the amount of time patients benefited from medication.

The dyskinetic side effects and the wearing off of levodopa are among “the most significant challenges with the current management of Parkinson’s disease,” says Todd Sherer, chief executive of the nonprofit Michael J. Fox Foundation, which funds Parkinson’s disease research. “It’s a trade-off between maximizing benefit and limiting the side effects.”

Several drugs already on the market reduce the off-time of levodopa by one to two hours. But many patients with advanced stages of the disease experience more than five hours of off-time daily. Also, these additional drugs may worsen dyskinesia.

The causes of Parkinson’s, a progressive neuromotor disease characterized by tremors, slow movements and impaired balance, are still being studied, but it has long been known that patients suffer from decreased amounts of dopamine.

In the late 1960s, doctors began using levodopa widely to treat Parkinson’s symptoms. It is still considered the best treatment, but with drawbacks. Too much levodopa can prompt dyskinesia over time, and sometimes visual hallucinations.

Dyskinesia affects patients differently. For Ed Ham, a 53-year-old who has had the disease for 15 years, it causes his head to bob uncontrollably and his right hand sometimes freezes into the shape of a gun. The movements don’t hurt, he says. However, the side effects take an emotional toll.

“Every day is a battle because you’re moving against yourself all the time,” says Mr. Ham, an insurance claims agent from Tampa, Fla.

In part because levodopa breaks down relatively quickly in the body, patients experience spikes of the medicine in their blood.

Gradually, however, as the dopamine cells die, patients often take increasing amounts of levodopa. Without the dopamine reserve, they become dependent on the drug and experience periods between doses in which the effects wear off. Dyskensia is thought to be linked to the dramatic swings in the amount of dopamine in the blood.

There could be big advances to come in the next couple of years, according to researchers. Some advances are focused on improvements to levodopa itself.

For instance, Impax Pharmaceuticals is working on a long-acting form of levodopa that would smooth out the treatment’s peaks and valleys. The company is working on securing Food and Drug Administration approval.

AbbVie’s gel is a combination of two existing medicines, levodopa and carbidopa, that enters the patient through an implanted pump.

In their first randomized, double-blind trial of the product, researchers compared the medication combination when administered through the pump vs. orally in 71 Parkinson’s patients who averaged levodopa off-time of six hours a day.

After 12 weeks, both groups showed a reduction in their off-time. However, the patients who received the medicine orally saw a decrease of two hours, while those who used the pump saw a four-hour reduction in off-time, a statistically significant improvement. There also was some improvement in dyskinesia.

Other researchers and companies are looking at enhancing levodopa’s potency through new treatment pathways. One getting attention is the adenosine 2a receptor, which interacts with nerves that respond to dopamine that are known to become overactive with levodopa use. It is novel because it doesn’t directly target the dopamine system, unlike drugs on the market.

Inhibiting A2a receptors could counteract some of the side effects of levodopa, according to C. Warren Olanow, a neurology professor at Mount Sinai Hospital in New York.

In a mid-stage clinical trial, tozadenant, being developed by Biotie and UCB, Inc., demonstrated a one-hour reduction in off-time for patients who received the optimal dose compared with placebo. That’s close to drugs already on the market, says Dr. Olanow, an investigator on the trial who presented the findings last week. The drug didn’t appear to worsen dyskinesia and appeared to induce few side effects, he says.

The company expects to run a late-stage clinical trial in 2015. Merck & Co. and others also have A2a antagonists in the works.

For patients, a better solution cannot come quickly enough. Jennilyn Merten, a 38-year-old filmmaker in New York, was diagnosed with early-onset Parkinson’s in 2008 after experiencing years of digestion problems, a gradual shaking in her left arm and, eventually, trouble walking.

Her neurologist warned her of levodopa’s wearing-off effect and the possibility of dyskinesia in four or five years.

Instead, Ms. Merten began noticing dyskinesia after just three months. It feels like an overwhelming urge to move, says Ms. Merten. She has left restaurants in the middle of dinner to do jumping jacks outside.

But she doesn’t dare to stop her levodopa treatment because of what happens when the drug wears off: She can’t think and her hands tighten up so she can’t type. Sometimes she literally freezes, she says.

“I’m basically going to be incapacitated by the drug that’s helping me, and that’s terrifying,” she says.

About bambooinnovator
Kee Koon Boon (“KB”) is the co-founder and director of HERO Investment Management which provides specialized fund management and investment advisory services to the ARCHEA Asia HERO Innovators Fund (www.heroinnovator.com), the only Asian SMID-cap tech-focused fund in the industry. KB is an internationally featured investor rooted in the principles of value investing for over a decade as a fund manager and analyst in the Asian capital markets who started his career at a boutique hedge fund in Singapore where he was with the firm since 2002 and was also part of the core investment committee in significantly outperforming the index in the 10-year-plus-old flagship Asian fund. He was also the portfolio manager for Asia-Pacific equities at Korea’s largest mutual fund company. Prior to setting up the H.E.R.O. Innovators Fund, KB was the Chief Investment Officer & CEO of a Singapore Registered Fund Management Company (RFMC) where he is responsible for listed Asian equity investments. KB had taught accounting at the Singapore Management University (SMU) as a faculty member and also pioneered the 15-week course on Accounting Fraud in Asia as an official module at SMU. KB remains grateful and honored to be invited by Singapore’s financial regulator Monetary Authority of Singapore (MAS) to present to their top management team about implementing a world’s first fact-based forward-looking fraud detection framework to bring about benefits for the capital markets in Singapore and for the public and investment community. KB also served the community in sharing his insights in writing articles about value investing and corporate governance in the media that include Business Times, Straits Times, Jakarta Post, Manual of Ideas, Investopedia, TedXWallStreet. He had also presented in top investment, banking and finance conferences in America, Italy, Sydney, Cape Town, HK, China. He has trained CEOs, entrepreneurs, CFOs, management executives in business strategy & business model innovation in Singapore, HK and China.

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