A potential long-acting treatment – GS-1614
The Calibr-Skaggs Institute for Innovative Medicines in La Jolla, California, conducts early-stage research with potential treatments for different infectious diseases.
Calibr has developed a potential HIV treatment code-named GS-1614 that has been licensed to Gilead Sciences for further development. Gilead will conduct studies of GS-1614 to better understand its safety and effectiveness as a potential treatment for HIV.
About GS-1614
GS-1614 is a pro-drug. Pro-drugs are medicines that are in one form but once taken into the body (either by pill or by injection) they are converted into an active drug. In the case of GS-1614, it is converted within the body to a drug called islatravir.
Islatravir belongs to a class of drugs called NRTTIs (nucleoside reverse transcriptase translocation inhibitors). Although this class of drug is relatively new (it was first discovered about a decade ago), islatravir has potent anti-HIV activity. It interferes with an enzyme used by HIV-infected cells called reverse transcriptase. It also interferes with HIV’s ability to take over an infected cell. It is possible that there may be other ways that islatravir works against this virus.
Perhaps most importantly, GS-1614 (and islatravir) have the potential to become long-acting treatments. The pharmaceutical company Merck is developing islatravir for clinical use. Gilead will cooperate with Merck to develop GS-1614 in combination with lenacapavir so that a dual long-acting regimen can be tested.
However, before that can happen, extensive research is needed to confirm the safety of GS-1614. In previous studies, Merck found that islatravir caused a temporary decrease in a group of cells called lymphocytes (commonly called B- and T-cells) in the blood of some people who used high doses of this drug. Subsequent clinical trials of islatravir are using much lower doses. Hopefully, the doses of GS-1614 selected for research in people will be sufficiently low that they do not cause this problem.
It is still too early in the development program for GS-1614 to determine if it will be successful. However, it is possible that within the next five years a combination of GS-1614 and lenacapavir could become an option for a long-acting HIV treatment, perhaps given every six months.
—Sean R. Hosein
REFERENCES:
- Scripps Research. Calibr announces license agreement with Gilead to develop a long-acting HIV antiviral agent for treatment in combination with lenacapavir. Press release. 4 January 2024.
- Merck. Merck announces clinical holds on studies evaluating islatravir for the treatment and prevention of HIV-1 infection. Press release. 13 December 2021.
- Merck. Merck to initiate new phase 3 clinical program with lower dose of daily oral islatravir in combination with doravirine for treatment of people with HIV-1 infection. Press release. 20 September 2022.