August 15, 2017
At each IAS conference, i-Base publishes a review of HIV drugs in development that summarises the most exciting new research over the previous year.
The following article is an update to the 2017 pipeline review, published just before IAS 2017.1
Several of the studies mentioned below are also reported in more detail later in this issue of HTB.
This is the first protease inhibitor based fixed dose combination (FDC). It contains darunavir/cobicistat/emtricitabine and tenofovir alafenamide (TAF).
IAS 2017 included interim results from a randomised phase 3 non-inferiority study in over 1100 people on stable boosted-PI plus TDF/FTC who switched to D/C/F/TAF or stayed on their current ART.2
The early results showed both groups continued to do very well with no significant differences in terms of viral rebound or side effects, although small improvement in kidney and bone monitoring were linked to the use of TAF in the FDC group.
The main study depends on 48-week results and another phase 3 study is also ongoing.
This compound was submitted to the regulatory agency in September 2016 and is likely to be the next HIV drug to be approved and available.
Please see the separate HTB report for full details.3
Bictegravir is a new once-daily integrase inhibitor that does not need boosting and that can be taken with or without food. It is only being developed as part of an FDC with FTC/TAF (B/F/TAF).
IAS 2017 included results from two large randomised phase 3 studies, each in more than 600 treatment naive participants.
One study compared B/F/TAF to the FDC dolutegravir/abacavir/3TC and the other to dolutegravir plus separate TDF/FTC.4,5
Both studies reported similar results for the active compared to control groups that fulfilled the criteria for non-inferiority. Small differences in side effects related mainly to the background nukes being used -- ie abacavir, TDF or TAF.
The bictegravir FDC was submitted to the FDA in June 2017 and to the EMA in July 2017. The FDA application included a priority review with a decision expected by February 2018.
Please see the separate HTB report for full details of both studies.6
Doravirine is a new once-daily NNRTI that is only being developed in an FDC with generic TDF and 3TC. This will have potential advantages of having a lower price compared to FDCs with fewer generic components but will also only be used in countries where the patent for TDF has either expired or is not enforced.
IAS 2017 included full results from a large randomised international phase 3 study in more than 700 treatment-naive participants comparing doravirine/FTC/TDF to efavirenz/FTC/TDF, with matching placebos.7
Full 48-week results reported similar virological results (84% vs 80% with viral load <50 copies/mL in the doravirine vs efavirenz arms) showing non-inferiority compared to efavirenz.
In this case, CNS-related side effects (interrupted sleep, dreams, mood changes) were significantly less with doravirine.
Please see the separate HTB report for full details of this study.8
A combined intramuscular injection containing two long-acting formulations has always generated a lot of interest for people wanting an alternating to daily oral ART.
IAS 2017 included longer follow-up -- now out to two years -- from a smaller early phase 2 study in about 280 treatment-naive participants.9
The results are slightly complicated by the study design, which includes a lead-in period using oral versions of both drugs, and the use of two different dosing schedules -- every 4 weeks and every 8 weeks -- plus a control group using oral cabotegravir plus abacavir/3TC.
In summary, results at week-96 were similar to those previously reported at week-48, with sustained viral suppression and low reports of side effects.
Even though injection site reactions were very common (in >80% of participants with the first dose and 30-40% throughout the study), these were usually mild and resolved within a week. Participants reported higher satisfaction with the injection formulation.
Full details are included in a separate HTB report.10
Ibalizumab is a monoclonal antibody that blocks HIV entry. It is given as an IV infusion every two or four weeks and has been in development for at least ten years.
IAS 2017 included results from a small phase 2b study in about 110 treatment-experienced participants with drug resistance to at least three other drug classes who used ibalizumab with optimised background therapy.
The study at IAS 2017 wasn't reporting overall results, but that ibalizumab remained similarly sensitive (or active) in people with a diverse range of drug resistance linked to current HIV classes.11
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