A Decades-Old Drug Technology Finally Nears Its Big Breakthrough - Bloomberg

Drugmakers are breathing new life into old drugs -- with hydrogen.

Substituting a heavier form of the gaseous element in drugs can slow their breakdown by the body, leaving them in the bloodstream longer. That means a patient can take them less frequently -- and that, in theory, might reduce the severity of side effects.

While the technology has been around for 40 years, it’s taken that long to understand it well enough to bring such a treatment before the U.S. Food and Drug Administration. The regulator is reviewing what would be the first medicine made with deuterium, or heavy hydrogen: a pill from Teva Pharmaceutical Industries Ltd. to treat a symptom of Huntington’s disease. The Israeli drugmaker plans to submit more data to the FDA by the end of the month, and is confident the drug will reach patients next year.

“This is a new concept, and FDA approval will make it a lot clearer for the field,” said Graham Timmins, an associate professor at the University of New Mexico who has studied the technology, known as deuteration.

Unique Properties

Should Teva get regulatory approval, it would open a market in the “many tens of billions of dollars,” said Roger Tung, whose company Concert Pharmaceuticals Inc. is also developing treatments with deuterium.

“It would show the breadth of possibilities,” Tung, the chief executive officer of Lexington, Massachusetts-based Concert, said in an interview. “Deuterium provides unique properties that cannot be attained in any other way.”

The approach interferes with one of the ways that the body metabolizes or eliminates drugs, involving enzymes that “nibble away” at the hydrogen in the molecule, Timmins said. Deuterium is essentially an armored hydrogen, tougher and more difficult for the enzymes to break down, so it sticks around longer in the body. Other than that, the drug works the same as the original.

Companies like Concert and Auspex Pharmaceuticals Inc., acquired by Teva last year for $3.5 billion, have built their businesses by patenting deuterated versions of marketed drugs, then testing them to make sure they’re safe and effective.

Opportunistic Approach

Concert takes “an opportunistic approach” to partnerships, Tung said. The company collaborates in some cases with the producers of the original drugs, though it doesn’t have a partnership with Vertex Pharmaceuticals Inc. on a deuterated version of Vertex’s Kalydeco treatment for cystic fibrosis. Vertex declined to comment on Concert’s product.

For each of its potential products, Concert has intellectual property rights in the U.S. and believes it has “freedom to operate,” Tung said.

Teva said it doesn’t have any licensing or royalty agreements on SD-809, and there is no litigation involving companies that sell tetrabenazine, the drug SD-809 is based on. H. Lundbeck A/S and Valeant Pharmaceuticals International Inc., which market tetrabenazine under the brand name Xenazine, declined to comment.

Sizable Market

Less than 10 percent of all FDA-approved drugs are amenable to deuteration because of their chemical structure, or because the body breaks them down in a way that isn’t affected by deuterium, Timmins said. That still represents a sizable market. For example, Kalydeco generated $631 million in sales for Vertex last year.

Most large drugmakers have filed patents on deuterated variants of their medicines, Timmins said. Concerns that manufacturing drugs with deuterium is costly has kept those companies on the sidelines, he said.

Teva is betting on deuteration as it searches for its next bestseller, a quest given added urgency after U.S. regulators recently invalidated the patents on the $4 billion drug Copaxone, paving the way for generic competitors.

Teva’s SD-809, a deuterated form of tetrabenazine, reduces the involuntary movements associated with Huntington’s disease, a genetic disorder that causes the progressive death of brain cells.

About 90 percent of the 40,000 Americans with Huntington’s disease suffer from the tics, Teva estimates, yet only about 10 percent of Huntington’s patients take tetrabenazine -- available in the U.S. since 2008 -- because of side effects including drowsiness and depression.

FDA Questions

“SD-809 could be a viable treatment option for many of these patients,” Mike Derkacz, Teva’s head of global central nervous system products, said in response to e-mailed questions. Derkacz didn’t specify details on pricing or sales estimates. Analysts predict about $1 billion in annual sales by 2022, roughly three times more than Lundbeck’s best year in Xenazine revenue.

First SD-809 needs to get past the FDA. The agency asked Teva to examine the blood levels of certain metabolites, or substances that result from the breakdown of medicines by the body.

One thing the FDA doesn’t require is data on how SD-809 performs against tetrabenazine. Teva isn’t planning a head-to-head trial, leaving open the question of whether SD-809 is truly better than the older drug.

Regardless, the modified drug would offer another option for many patients’ families. The tics that accompany Huntington’s are “a big stress on the families,” said Louise Vetter, CEO of Huntington’s Disease Society of America, a U.S. non-profit that funds research and support programs for families affected by the disease.

“We don’t endorse therapies or do targeted outreach,” Vetter said. “But we would celebrate and trumpet the news of an approved drug.”

An approval would probably spur more interest in deuteration, said Nick Paras, a medicinal chemist and associate adjunct professor at the University of California San Francisco’s Institute for Neurodegenerative Diseases.

“In the right situation with the right compound, it can have a dramatic effect,” Paras said. “It’s going to be a great addition to the drug discovery toolbox.”

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