Doravirine FDC submitted to FDA in US: decision expected October 2018

22 January 2018. Related: Antiretrovirals.

Simon Collins, HIV i-Base

On 8 January 2018, Merck announced that two new applications for the NNRTI doravirine (formally MK-1439) have been submitted to the US FDA. [1]

One application is as a separate drug and the second is as part of a fixed dose combination (FDC) with two generic tenofovir DF (TDF) and generic lamivudine (3TC).

Applications are based on 48-week results from two ongoing randomised, double-blind phase 3 studies in treatment naive participants with darunavir and efavirenz used as comparitor drugs.

The DRIVE-FORWARD study randomised 768 treatment naive participants to either doravirine or darunavir/r, stratified by baseline viral load (</> 5 log) and investigator selected NRTI backbone. For the primary endpoint, viral load was <50 copies/mL in 84% vs 80% in the doravirine vs darunavir arms respectively (difference: +3.9%, 95%CI: –1.6 to +9.4). [2]

Using a similar design, the DRIVE-AHEAD study randomised 734 treatment-naive participants to either the a doravirine FDC or efavirenz FDC, both coformulated with TDF/FTC. At week 48, viral load was < 50 copies/mL was achieved by 84% vs 80% in the doravirine vs efavirenz arms respectively (difference: +3.5%, 95%CI: –2.0 to +9.0). [3]

The FDA decision will be announced by 23 October 2018.

References

1. Merck press statement. FDA accepts new drug applications for Merck’s doravirine, the company’s investigational non-nucleoside reverse transcriptase inhibitor (NNRTI), for treatment of HIV-1 infection. (08 January 2018)
   http://investors.merck.com/news/press-release-details/2018/FDA-Accepts-New-Drug-Applications-for-Mercks-Doravirine-the-Companys-Investigational-Non-Nucleoside-Reverse-Transcriptase-Inhibitor-NNRTI-for-Treatment-of-HIV-1-Infection/default.aspx
2. Molina J-M et al. Doravirine is non-inferior to darunavir/r in phase 3 treatment-naive trial at week 48. CROI 2017, 13-16 February 2017, Seattle. Late breaker oral abstract 45LB.
   http://www.croiconference.org/sessions/doravirine-non-inferior-darunavirr-phase-3-treatment-naïve-trial-week-48
3. Squires K et al. Fixed dose combination of doravirine/lamivudine/TDF is non-inferior to efavirenz/emtricitabine/TDF in treatment-naive adults with HIV-1 infection: week 48 results of the Phase 3 DRIVE-AHEAD study. IAS 2017, 23-26 July, Paris. Oral late-breaker abstract TUAB0104LB.
   http://programme.ias2017.org/Abstract/Abstract/5585