Concert Starts HIV Trial, Bags $12M From Glaxo to Help Challenge Gilead’s Once-Daily Pill

11/9/09Follow @xconomy

Concert Pharmaceuticals, the Lexington, MA-based company that chemically modifies existing drugs to make them more attractive, has started human testing of an HIV medication which it hopes will help GlaxoSmithKline wrestle back market share it has been losing to Gilead Sciences, the world’s largest maker of HIV drugs.

Concert will receive a $12 million payment from GlaxoSmithKline for starting the trial of a drug it calls CTP-518. It’s one small piece of the collaboration announced in June that could be worth more than $1 billion over time to the smaller company. I heard about this bit of news, and what it means strategically to Concert, when I visited CEO Roger Tung at the company’s office last week.

The basic idea is to take a common protease inhibitor, Bristol-Myers Squibb’s atazanavir (Reyataz), and swap out a few hydrogen atoms on the molecule with deuterium atoms. This is supposed to retain the drug’s viral killing punch, while making it last longer in the body. That’s desirable because it could allow doctors to quit prescribing a booster drug from Abbott Laboratories called ritonavir that adds cost, complexity, and hassles, Tung says. If the Concert drug is able to remain potent long enough in the bloodstream on its own, then it could be combined with other antivirals to create a convenient once-daily pill to compete with Gilead Sciences’ efavirenz emtricitabine tenofovir (Atripla), a drug that has helped Gilead surpass Glaxo as the world’s leading maker of HIV drugs the past couple of years.

“Doctors don’t like prescribing ritonavir, and patients don’t like taking it,” Tung says. “Our hope is to take a great drug and make it more tolerable and easier to take. The idea is to be the most tolerable, best-in-class HIV inhibitor.”

Without going too far into how this works, Concert says the deuterium atoms it is swapping into CTP-518 are supposed to form stronger bonds to the rest of the molecule than the traditional hydrogen bonds. By creating a more bulletproof package that stands up to the usual digestive processes, a greater amount of the drug and desirable metabolic byproducts are supposed to make it through the intestines and into the bloodstream, Tung says. That means the Concert drug should cause less irritation in the gut that can lead to diarrhea and nausea, and that it can use lower doses to get the same amount of drug into the bloodstream.

Getting rid of the ritonavir booster drug is important, Tung says, because it needs to be kept refrigerated in warm environments, making it a hassle for patients to travel with it and take it to work. It’s also an extra co-pay for patients, and can cause some nausea and increases in blood lipids, although he acknowledged the drug is “reasonably safe.”

Convenience might sound like something nice for a marketing campaign but trivial in the medical sense, but that’s not the case with HIV. Since the virus has such crafty ability to mutate, patients need to stay on their cocktail regimens on a consistent basis, and if they don’t, they are potentially creating an opportunity for the virus to flourish and develop resistance to treatment.

While making drugs more convenient to take is absolutely part of the long-range strategy of Concert, the company still has a really long way to go to prove this idea. This Phase 1 clinical trial will enroll healthy volunteers who will get multiple escalating doses to test the safety and tolerability of the product. The trial will also look to see if the drug can maintain concentrations in the bloodstream that are good enough to hold the virus in check with a once-daily dose, when combined with other drugs. Patients will be randomly assigned to get the Concert drug or a placebo for 14 days.

After the Phase I trials are finished, GlaxoSmithKline will have the option to take an exclusive, worldwide license to develop and commercialize the Concert drug.

It’s still too early to say whether Glaxo will want that option, or whether Concert will be on its own to find another partner for the HIV drug. But Tung says he likes the fact that Glaxo and Pfizer have decided to pool their HIV efforts in a joint venture to better compete with Gilead. Inside a joint venture with its own management team, the Concert program is likely to get more attention than it would as one of “a million other things” Glaxo has in its development portfolio, Tung says.

“This is great for us,” Tung says. “This drug is absolutely our world. We’ve got to make it work for us, for patients, and partners.”

Plus, while $12 million may not be much to GlaxoSmithKline, it’s a hefty boost for Concert and its team of 47 employees. The latest boost means the company now has more than two years of operating cash in the bank, Tung says.

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