- Merck & Co.'s wavering virology business got fresh blood Thursday, as the company announced two of its new HIV medications received approval from the Food and Drug Administration.
- Branded as Pifeltro and Delstrigo, the oral medications are taken once-daily with or without food for adult HIV-1 patients who have never received antiretroviral treatment. Merck's investigational drug doravirine is the sole active ingredient in Pifeltro, while Delstrigo pairs that drug in a fixed-dose combination tablet with lamivudine and tenofovir disoproxil.
- Regulators based the approvals on data from the Phase 3 DRIVE-AHEAD and DRIVE-FORWARD studies. In the former, Delstrigo showed non-inferiority to Gilead Sciences' Atripla. In the latter, Pifeltro showed non-inferiority to Johnson & Johnson's Prezista plus 100 mg of ritonavir. Both treatments in DRIVE-FORWARD were administered in combination with either Gilead's Truvada or Epzicom/Kivexa.
Year-over-year sales of the big pharma's HIV drug Isentress (raltegravir) were flat during the first six months of 2018, while sales of its hepatitis C medicine Zepatier (elbasvir/grazoprevir) plummeted more than 70% from the same period in 2017.
Additionally, Merck helps commercialize Gilead's Atripla (efavirenz/emtricitabine/tenofovir disoproxil fumarate) outside the U.S. But the global HIV market is crowding with new therapies, threatening Atripla's share.
New products could therefore help Merck prop up virology sales. Market research firm GlobalData predicts that, by 2023, Pifeltro and Delstrigo will bring in around $500 million combined across the seven major pharmaceutical markets of France, Germany, Italy, Japan, Spain, the U.K. and the U.S.
"Although the combined sales of Delstrigo and Pifeltro are unlikely to match the highly successful Atripla, they are still expected to be well received by physicians, aided by the inclusion of treatment-naïve patients in yesterday’s FDA indication," Thomas Moore, senior pharma analyst at GlobalData, said in an Aug. 31 commentary.
Others, however, appear less convinced about the drugs' potential, in good part because of the resistance to doravirine that some patients demonstrated in clinical testing.
Across the DRIVE-AHEAD and DRIVE-FORWARD studies, 11 participants showed the emergence of doravirine-associated resistance substitutions. Though a similar number of participants in the DRIVE-AHEAD showed the emergence of efavirenz-associated resistance substitutions, no one in DRIVE-FORWARD showed the emergence of darunavir plus ritonavir-associated resistance substitutions.
"The doravarine triple was no more effective than the boosted protease inhibitor (PI), no better tolerated, and had two cases of treatment-emergent NNRTI resistance," Leerink analyst Geoffrey Porges wrote in a July note to Gilead investors.
"This means that doravarine based combinations are unlikely to be viable as two-drug regimens, and furthermore, are unlikely to compete with Biktarvy, Triumeq, Juluca and [dolutegravir/lamivudine] for the heart of the first line HIV treatment market."
Merck noted investigators haven't seen any significant cross-resistance between doravirine-resistant HIV-1 variants and lamivudine, emtricitabine or tenofovir — or between 3TC or tenofovir-resistant variants and doravirine.
While Delstrigo and Pifeltro may not be blockbuster hopefuls, Merck executives said the drugs still hold long-term value for the company's HIV business. Adam Schechter, president of global human health, argues that as a non-nucleoside reverse transcriptase inhibitor (NNRTI), doravarine adds diversity to Merck's portfolio and sets a strong tone for its other NNRTI asset, called MK-8591.
"It's important to have options outside the integrase inhibitor class," Schechter said on Merck's second quarter earnings call, adding that "NNRTI-based regimens are one of the most commonly used treatment regimens in early-line patient populations, and if you look doravarine's profile, it does improve on some of the limitations with the NNRTI class."
"But I look at it more as a bridge," he said. "It's a way to continue to build on our legacy in HIV, a bridge to ... MK-8591 ... So I would look at it as a near-term way for us to continue to be relevant in the market, but a real growth opportunity as we bridge into the future with our pipeline."