The U.S. Food and Drug Administration recently approved GSK’s combination drug Dovato (dolutegravir/lamivudine) for the treatment of HIV-1 infection. However, physicians raised concerns over a possible drug resistance to the combo and the lack of long-term clinical data.

GSK’s combination drug Dovato (dolutegravir/lamivudine) for the treatment of HIV-1 infection

Upon the FDA’s nod Monday, once-daily Dovato was authorized to treat HIV-1 infection in adult patients with no antiretroviral treatment history and with no known resistance to either dolutegravir (DTG) or lamivudine (3TC).

GSK emphasized that Dovato’s combo of DTG and 3TC into a single tablet helped HIV patients, who have to take the medications for a lifetime, citing GEMINI 1 and 2 studies on more than 1,400 adult patients with HIV-1 infection.

According to the results of the two studies, the DTG+3TC therapy showed the non-inferior antiviral effect to the three-regiment treatment of DTG+tenofovir disoproxil fumarate+emtricitabine at week 48.

The combo therapy did not show any different safety profile from those labeled on DTG and 3TC, respectively. During the trials, no patient developed resistance requiring urgent medical care.

“Treatment-naïve people living with the virus have a powerful option that delivers non-inferior efficacy to a DTG-based three-drug regimen, allowing them to take fewer antiretrovirals and get and remain suppressed,” said Pedro Cahn, principal investigator for the GEMINI study program.

However, industry people and medical professionals said they had some doubts about GSK’s new combo.

Fierce Pharma, a U.S. media covering pharmaceutical and biotech news, said GSK’s Dovato had a unique safety problem, in addition to the warning that HIV patients accompanying hepatitis B should take caution just like those who take Gilead’s three-regimen cocktail Biktarvy by Gilead.

FDA warned neural tube congenital disabilities in babies born to women treated with DTG, asking patients to avoid Dovato use at the early stage of pregnancy.

Doctors said the DTG+3TC combo might not be strong enough to show long-term antiretroviral efficacy.

A single nucleoside reverse transcriptase inhibitor (NRTI), rather than the two in current standard treatments, could make patients easily develop treatment resistance, Fierce Pharma said.

Sorana Segal-Maurer, chief of the infectious disease division at New York-Presbyterian Queens Hospital, also raised concern over the GSK drug in an e-mail interview with Korea Biomedical Review.

Segal-Maurer said DTG has a long half-life, about 16-17 hours, whereas 3TC has a short one. If patients do not take the two on time, the DTG level in the blood will be maintained, but that of 3TC will fall as if a patient received a monotherapy of DTG, she explained.

She took the example of a study that tested DTG as a monotherapy. Some patients showed resistance in a taking-turn-administration setting, which made the study halt, she noted. “Therefore, I do not recommend taking DTG only,” Segal-Maurer said.

“The clinical trial on DTG+3TC set the patient group very carefully. The patients’ viral load was not high, and their T-cell levels were not low. The results came positive, but we have to see if the efficacy will be maintained after five years,” she added.

Fierce Pharma also said, “No treatment-emergent resistance occurred in the Gemini trials. Again, however, these are just one-year results that won’t likely quash skepticism over the possibility of treatment-related resistance in the long run.”

kym@docdocdoc.co.kr

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