Decades-old drug technology finally nears its big breakthrough

Tel Aviv

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. This means that 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 has taken that long to understand it well enough to bring such a treatment before the US Food and Drug Administration (FDA). 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 that 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.

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," said Mr Tung, the chief executive officer of Lexington, Massachusetts-based Concert. "Deuterium provides unique properties that cannot be attained in any other way."

The approach interferes with one of the ways that the body metabolises or eliminates drugs, involving enzymes that "nibble away" at the hydrogen in the molecule, Mr Timmins said. Deuterium is essentially an armoured 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 such as Concert and Auspex Pharmaceuticals Inc, acquired by Teva last year for US$3.5 billion, have built their businesses by patenting deuterated versions of marketed drugs, then testing them to make sure that they are safe and effective.

Concert takes "an opportunistic approach" to partnerships, Mr Tung said. The company collaborates in some cases with the producers of the original drugs, though it does not 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 US and believes that it has "freedom to operate", Mr Tung said.

Teva said it does not have any licensing or royalty agreements on SD-809, and there is no litigation involving companies that sell tetrabenazine, the drug that SD-809 is based on.

Less than 10 per cent 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 is not affected by deuterium, Mr Timmins said. That still represents a sizable market. For example, Kalydeco generated US$631 million in sales for Vertex last year.

Most large drugmakers have filed patents on deuterated variants of their medicines, Mr Timmins added. 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 US regulators recently invalidated the patents on the US$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 per cent of the 40,000 Americans with Huntington's disease suffer from the tics, Teva estimated, yet only about 10 per cent of Huntington's patients take tetrabenazine - available in the US since 2008 - because of side effects including drowsiness and depression.

"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. Mr Derkacz did not specify details on pricing or sales estimates. Analysts predict about US$1 billion in annual sales by 2022, roughly three times more than Lundbeck's best year in Xenazine revenue. Bloomberg