The FDA has approved two new antiretroviral medications for those just starting HIV treatment. Pifeltro (doravirine) is a new non-nucleoside reverse transcriptase inhibitor, while Delstrigo (doravirine/lamivudine/tenofovir disoproxil fumarate) includes a NNRTI and two nucleoside reverse transcriptase inhibitors. Both drugs are manufactured by Merck, and should be taken orally, once daily, for HIV-positive adults with no history of antiretroviral treatment.
While Pifeltro is prescribed in combination with other HIV meds, Delstrigo is a stand-alone, single-tablet regimen. Dr. Carey Hwang, executive director of infectious diseases, global clinical development at Merck Research Laboratories says having another single-tablet option is important because, “There are some studies which suggest better adherence with once-daily antiretroviral regimens compared to older regimens or multiple pill regimens,” Hwang says. “Tolerability of a treatment plays an important role in adherence, as missed doses may lead to the development of viral drug resistance.”
One of the studies that served as the basis for the approval is known as DRIVE-FORWARD, which showed a statistically significant lower proportion of participants taking Delstrigo reported fewer “neuropsychiatric adverse events” or side effects than those taking efavirenz (brand name Sustiva), including dizziness (9 percent on Delstrigo reported this, versus 37 percent on efavirenz), sleep disorders and disturbances (12 percent vs 26 percent), and an inability to think clearly or concentrate (4 percent versus 8 percent).
More importantly, through 48 weeks of treatment, fewer Delstrigo-treated participants developed viral drug resistance than those in the efavirenz-treatment group. Developing drug resistance is a significant problem for those with HIV, and any drug with less risk of developing resistance is a welcome addition to the HIV medicine chest.
When it comes to Pifeltro, Hwang says “doravirine is potent and has been shown to be non-inferior in two Phase Three clinical trials against well-established comparators. I think it addresses several of the issues that have been associated with the first and second generation antiretroviral drugs in the class, such as neuropsychiatric adverse events, requirements to take with a high fat meal and some of the drug interactions.” Neither Delstrigo nor Pifeltro need to be taken with a meal.
In trials, Pifeltro demonstrated sustained viral suppression compared to DRV+r (darunavir plus ritonavir), each in combination with Truvada (emtricitabine and tenofovir disoproxil fumarate). For example, 84 percent of those on Pifeltro and Truvada achieved viral suppression compared to 80 percent of those on DRV+r and Truvada. Greater success in reaching viral suppression is particularly important because becoming undetectable makes it virtually impossible to transmit HIV.
Those on Pifeltro also demonstrated statistically significant impacts in reducing “bad” cholesterol levels — although researchers say the health benefit of these findings have not been evaluated.
Explaining how the process worked from the development of Merck’s innovative therapy to FDA approval, Hwang says, “These are large trials that we sponsor and we enlist investigators worldwide to enroll participants into the trials to evaluate doravirine against other approved antiretrovirals. The primary efficacy endpoint is looking at whether, in this case doravirine, is non-inferior to our competitor FDA-approved comparator drugs that are currently on the market.”
Pharma companies must show their drug is at least as good as competitive medications already on the market. Ideally, they want to show — as Merck has with both Pifeltro and Delstrigo — that the new medication has advantages compared to other drugs.
Dr. Hwang’s career HIV has spanned decades, and ranged from collecting blood samples to patient care to clinical research and the development of new drugs. “I treated patients with HIV in the clinic... at Vanderbilt. You develop one-on-one relationships with patients to help them on an individual level to successfully treat their HIV. [But] if you can help develop a drug that improves the lives of people living with HIV, you can potentially positively impact thousands, if not millions of lives.”
Pifeltro (DOR) is also being evaluated in a Phase 3 trial called DRIVE-SHIFT, a trial evaluating if those who have HIV and are currently virologically suppressed on another antiretroviral regimen can switch to Pifeltro and Truvada without having their viral loads rebound. If that trial is successful, Pifeltro will also be available for those looking to switch medications — rather than limited to those new to treatment, which is what it has currently been approved for.