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GlaxoSmithKline has entered into a collaboration deal with Concert to create drugs using deuterium-“heavy hydrogen”-that can be gathered from seawater and used to alter the way molecules perform in the body.
A potentially powerful new technology found a big-pharma sponsor this week as GlaxoSmithKline announced on Tuesday that it had signed a collaboration agreement with three-year-old biotech firm Concert Pharmaceuticals.
The deal provides Concert with $35 million up-front and up to a billion dollars in milestone payments. Under the terms of the agreement, Concert will develop three of its compounds through agreed-upon clinical trials, at which point GSK will have an option to obtain an exclusive worldwide license to them. Concert will also provide versions of three GSK pipeline drugs modified using Concert’s innovative deuterium technology
The technology involves replacing ordinary hydrogen atoms certain existing drug molecules with deuterium-also known as “heavy hydrogen-an isotope of hydrogen in which the nucleus contains one proton and one neutron. (In ordinary hydrogen the nucleus consists only a single proton.) Deuterium, which is easily isolated from seawater, has twice the atomic mass as ordinary hydrogen, which means that it bonds differently with other elements-for instance, forming a much stronger bond with carbon.
According to GSK, Concert has demonstrated that this increased bond strength, in select cases, can be used to improve important drug properties including bioavailability, half life, and levels of beneficial or undesired metabolites,. The resulting novel compound has the potential for improved drug efficacy, safety, and tolerability.
“A drug with deuterium in it will have the same pharmacological effect as a drug with hydrogen, but the metabolism can be significantly changed,” said Roger Tung, president and CEO of Concert Pharmaceuticals. For example, one of the drugs covered by the agreement is Concert’s CTP 518, a protease inhibitor created by substituting deuterium for hydrogen in some key locations in atanazanavir. In preclinical studies, CTP 518 maintained full antiviral potency, but with significantly slower metabolism in the liver. The hope is that because it will be easier to maintain higher blood levels of CTP 518, the drug will become the first protease inhibitor to be used without a booster drug such as ritonavir.
“It’s this process of being able to fine-tune the fate of the drug after it enters the body that allows us to start with something with known activity and enhance it in ways that make it a better drug,” Tung said.
One of the advantages of the deuterium technology is that it can change the properties of molecules whose actions are already known. “When you look at the overall costs of R&D, the majority of costs are due to drugs failing in the clinic,” Tung said. “So you put a tremendous amount of time and effort in getting a compound to get into clinical trials in humans and then the trials are long and expensive. And if the drug fails, it could be a huge lost cost-into the millions of dollars.”
“In terms of the benefits we would we expect to see of deuterium-modifying the three GSK pipeline products, the answer depends on the GSK compound in question,” a spokesperson at GSK told Pharm Exec. “However, potential effects-all of which are the result of modifying drug metabolism-may include enhanced safety profiles, increased therapeutic index, improved dosing regimens.”
Concert said that this agreement follows their corporate strategy to partner certain programs while independently advancing others.
“GSK will help us in a number of ways,” Tung said. “They offer a validation for the technology. Deuterium is not an atom that has ever been used in a human drug before. It has been used in metabolic probes, and in compounds that have been studied scientifically, but it has never been used in people as an approved agent. With GSK’s knowledge of approved pharmaceuticals, they believe that you can get drugs made this way and the answer to that is obviously yes, or they wouldn’t be paying us this much money.
“We have very clearly demonstrated that we are the leading company in the application of deuterium to pharmaceuticals,” Tung said. “It’s creating a new platform with substantial opportunity for creating a lot of important products in a situation where pharma companies are looking for products and I think it’s the right kind of technology for the current times.”