Concert Pharmaceuticals caught my eye a few weeks back with something unusual—an experimental drug for the hot flashes women get during menopause, without the risks of standard hormone-replacement therapy.

I didn’t have a chance to interview CEO Roger Tung last month when his Lexington, MA-based company took this drug into its first clinical trial, so a follow-up was in order. Tung bears watching because he was one of the people who left Merck with Joshua Boger in 1989, and became employee No. 9 at Cambridge, MA-based Vertex Pharmaceuticals, where he stayed until 2005.

Tung’s new company got off to an auspicious start the next year with a long list of venture capital backers, and he has shown good timing. Tung raised a $37 million round in May for Concert that will help it weather the financial storm through 2010, he says

So what does Concert have under the hood? It takes existing drugs that have well-understood safety profiles, replaces a few hydrogen atoms with deuterium atoms to change how they are metabolized, and sees if that can give the drugs enhanced properties such as fewer drug-drug interactions or more stable absorption, Tung says. (It also creates a newly-patentable set of compounds for Concert.) The company’s lead candidate, CTP-347, is a modified form of paroxetine, long marketed by GlaxoSmithKline as the anti-depression drug Paxil. This drug is off-patent, and reached $3 billion in annual sales at its peak, so a lot is known about its safety profile. Nobody had ever developed it for hot flashes, and no alternatives for hot flashes exist beyond hormone-replacement therapies, which many women avoid because of the risks (a bit more on this below).

“I wanted to create a differentiated compound with real benefit for medicine, strong reimbursement profile, lower development risk, and shorter timelines,” Tung says.

By taking paroxetine and replacing certain hydrogen atoms with deuterium, Concert believes it has found a way to get the benefits against hot flashes without the side effects. Wyeth’s Pristiq, another anti-depression drug, showed a benefit last year against hot flashes in a clinical trial and a trial published in the Journal of the American Medical Association suggests paroxetine may work for hot flashes at lower doses than for depression, Tung says. The Concert drug has another advantage of minimizing the older paroxetine’s action against a key liver enzyme for drug metabolism, CYP2D6. That enzyme is needed to break down tamoxifen, a drug taken by millions of menopausal women to prevent breast cancer. Interfering with that enzyme can cause what amounts to a traffic jam in the liver, leading to side effects. It only makes sense that any new drug for hot flashes will have to behave well in tandem with tamoxifen.

Hormone replacement therapies like Wyeth’s Prempro work against hot flashes, but the landmark Women’s Health Initiative results in 2002 showed the drugs can raise the risk of breast cancer and heart attacks for some women. An estimated 8 million women quit taking the hormone-replacement meds after that study, Tung says, so there’s a big potential market here for something perceived as less risky.

The deuterium itself is not a problem, because it’s cheap and widely available, derived from sea water. Concert’s chemists were able to synthesize it into the new drug so quickly that they zipped through animal tests and entered the clinic in two years, Tung says. Results from this early-stage trial will be available in the first half of 2009, which will give the company an idea about whether it can avoid bad drug-drug interactions.

Concert’s second candidate is a protease inhibitor for HIV, modified with deuterium, …Next Page »

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Concert Pharmaceuticals is moving ahead with a drug that it hopes will be the first of its kind to treat the hot flashes women get during menopause, without exposing them to the well-documented risks of hormone-replacement therapy.

The Lexington, MA-based company said today it has begun its first clinical trial with a drug candidate called CTP-347. The company combined the news with another announcement that clearly gave it confidence to move ahead: Animal tests reveal its drug can avoid bad drug-drug interactions with tamoxifen, a common breast cancer drug, according to research presented at the North American Menopause Society’s meeting in Orlando.

As we reported back in May, the drug is made by replacing a few hydrogen atoms on a drug called paroxetine with deuterium atoms. That chemical trick allows Concert to retain the action of paroxetine against hot flashes, while minimizing its ability to block a critical liver enzyme for drug metabolism, CYP2D6. Since tamoxifen—a drug taken by millions of menopausal women to combat breast cancer risk—is metabolized by that enzyme, interfering with it could cause problems. Basically, if you gave it in combination with paroxetine, it could cause a big-time traffic jam at that enzyme, causing the drugs to build up in the body and cause side effects.

“We believe our deuterium chemistry platform holds great promise in creating novel compounds with superior safety and efficacy as compared to existing therapies,” said Roger Tung, Concert’s CEO, in a statement.

Concert raised $37 million from a syndicate of investors in May, including new investors Adage Capital Management, SR One, Mediphase Venture Partners, and Westfield Capital Management, as well as existing investors including Three Arch Partners, TVM Capital, Skyline Ventures, Brookside Capital Partners Fund, Flagship Ventures, Greylock Partners, New Leaf Venture Partners, and QVT Fund.

Results from the Phase I clinical trial in hot flashes are expected in the first half of 2009, so those investors will start to get a read on whether the new drug has an ability to avoid toxic drug-drug interactions in people as well as animals. Since this candidate took less than two years to bring to clinical trials, if it demonstrates safety in Phase I, other modified drugs with deuterium may not be far behind.

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