Doravirine Demonstrates Strong 96-Week HIV Viral-Suppression Results

Carey Hwang, MD, PhD

Merck & Co. says its investigational non-nucleoside reverse transcriptase inhibitor (NNRTI) continues to perform well at 96 weeks, outpacing a common existing treatment in achieving viral suppression.

Merck announced the most recent data on doravirine at the 22nd annual International AIDS Conference in Amsterdam last month. The results show 73.1% of patients (277 of 379) on once-daily doravirine had achieved viral suppression at 96 weeks.

That’s better than the 66% of patients (248 of 376) in the study who achieved viral suppression after taking once-daily ritonavir-boosted darunavir (DRV+r). Darunavir is sold under the brand name Prezista by Johnson & Johnson and was first approved in 2006. Ritonavir is sold by AbbVie under the name Norvir.

The new data are similar to the 48-week results for the therapy, and they provide the company a boost as it heads before the US Food and Drug Administration (FDA) for approval to market the drug.

Carey Hwang, MD, PhD, who leads the product development team for doravirine at Merck, said he believes the new drug will be an important addition to the lineup of NNRTIs on the market, because it addresses some of the issues physicians and patients face with existing NNRTIs, including drug interactions and side effects like hyperlipidemia.

“The logical place for doravirine is in patients who are currently on NNRTIs and want to upgrade within the same class to a new compound that addresses a lot of those previous issues,” Hwang told MD Magazine®.

The most common adverse effects among patients in the study’s doravirine cohort were diarrhea, nausea, headaches, upper respiratory infection, and viral upper respiratory infection. Adverse effects led 1.6% of participants in the doravirine group to drop out of the study; the adverse effect dropout rate for the DRV+r group was 3.4%.

Among patients who entered the study with a high baseline viral load (defined as HIV-1 RNA levels of greater than 100,000 copies/mL), doravirine’s results were similar to, but not better than DRV+r, with 65.4% of 78 patients achieving viral suppression on doravirine versus 65.2% of the 66 patients on DRV+r achieving the same.

Hwang said the lower efficacy rate among those with a higher baseline viral load was not a surprise.

“In that population with higher viral loads, if you look at all the trials across the board the response rate or efficacy rate is usually lower,” he said, adding that by 96 weeks, a number of patients have discontinued their participation in the study, thereby affecting the data.

In January, Merck submitted new drug applications to the FDA aiming to get doravirine approved for treatment-naive HIV-1-positive adults. Those applications seek approval for doravirine as a once-daily tablet for use in combination with other antiretroviral drugs, and for use of doravirine with lamivudine and tenofovir disoproxil fumarate in a once-daily fixed-dose combination single tablet as a complete regimen. The FDA has set a target date of Oct. 23 for its decision.

In the meantime, Merck continues to research doravirine, with several Phase II and III studies ongoing.