Glaxo to test rival's protease inhibitor, re-engineered to last longer

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GlaxoSmithKline announced today that it has signed a development deal with Concert Pharmaceuticals for a new protease inhibitor, engineered to avoid the need for any sort of boosting agent.

CTP-518 is a modified form of the HIV protease inhibitor atazanavir in which key hydrogen atoms have been replaced by deuterium, a heavier relative of hydrogen. The drug’s developers believe that using deuterium will slow the rate at which the drug is eliminated from the body, thus achieving higher trough levels and potentially eliminating the need for boosting with ritonavir or another agent.

The advantage of dispensing with a boosting agent is that the product will cost less to use, and without ritonavir boosting, may carry a lower risk of triglyceride elevation.

Glossary

boosting agent

Booster drugs are used to ‘boost’ the effects of protease inhibitors and some other antiretrovirals. Adding a small dose of a booster drug to an antiretroviral makes the liver break down the primary drug more slowly, which means that it stays in the body for longer times or at higher levels. Without the boosting agent, the prescribed dose of the primary drug would be ineffective.

triglycerides

A blood fat (lipid). High levels are associated with atherosclerosis and are a risk factor for heart disease.

 

phase I

The first stage of human testing of a new drug or intervention, typically involving a small number (10-100) of participants who do not have the condition the drug is intended to treat. Phase I clinical trials evaluate safety, side-effects, dosage and how a drug is metabolised and excreted in the body.

Even though atazanavir, the best selling protease inhibitor in the US, is owned by Bristol Myers Squibb and marketed as Reyataz, Concert Pharmaceuticals has been granted a patent on its version of the drug. Concert Pharmaceuticals has also patented a deuterated version of darunavir, another protease inhibitor that must be boosted with ritonavir.

The drug will enter phase I studies shortly and GlaxoSmithKline has the option of subsequent commercialisation. Deuterated agents may not have the same toxicological and pharmacological data requirements as completely new agents, allowing developers to carry out studies for registration more quickly, according to a recent review in Drug Development and Discovery.