“A multi-pronged approach will likely be needed to achieve the goal of curing HIV”

January 6, 2020 0 By S Harachand

Despite tremendous advances in the field, HIV is still an epidemic with a heavy impact on marginalised populations. Gilead has been at the forefront of developing innovative medicines to combat the disease for over 30 years.  A pioneer in HIV research, the company believes that through relentless pursuit for a cure, the HIV epidemic can be ended once and for all.
Edited excerpts from an interview with Devi SenGupta, Senior Director, HIV & Emerging Viruses, Gilead Sciences

Gilead’s HIV treatments pipeline shows three drug candidates belonging to three different classes of drugs. What is the rationale for choosing such a diverse drug pipeline?

Gilead pioneered the first single-tablet regimen that helped transform the standard of care for HIV. Since then, we’ve introduced five additional single-tablet regimens to help meet the evolving needs of people living with HIV, constantly innovating in order to expand treatment options

Progress in treatment has been transformative; but, significant gaps in care still remain. New medicines are needed to support unmet and evolving medical needs in HIV.

To that end, we take a multipronged approach aimed at researching investigational new agents that may be active against resistant variants of HIV and target novel mechanisms of action, with the goal of providing simple and efficacious treatment options to all people living with HIV, irrespective of their prior treatment history.

Gilead has recently reported encouraging phase 1 data on GS-6207 as a long-acting injectable therapy. What is the potential of capsid inhibitors in tackling HIV resistance? 

Adherence to HIV therapy is critical to ensuring viral suppression and preventing the potential development of drug resistance. Resistance can limit a person’s HIV treatment options by reducing the effectiveness of a particular HIV drug or class of drugs. Drug resistance can also be transmitted, so a person can be infected with a resistant strain of HIV and have limited treatment options before ever starting therapy.

GS-6207 is an investigational agent that is being developed as a component of a potential future long-acting, injectable HIV treatment regimen. Results from in vitro virology studies presented at the 17th European AIDS Conference suggest a very low likelihood of pre-existing resistance mutations against GS-6207 among people living with HIV.

GS-6207’s multi-stage mechanism of action profile is distinguishable from currently approved classes of antiretroviral agents. The drug interrupts the activity of the HIV capsid, a protein that surrounds and protects the virus’ genetic material and essential enzymes. It may interrupt multiple distinct stages of the viral lifecycle, potentially preventing the virus from becoming infectious and gaining access to uninfected cells.

We believe GS-6207 could be part of a future long-acting combination therapy for a broad patient population. The FDA granted Breakthrough Therapy Designation for the development of GS-6207 for the treatment of HIV-1 infection in heavily treatment-experienced patients with multi-drug resistance, when used in combination with other antiretroviral drugs.

Based on promising results from in vitro and Phase 1 clinical trials, we will soon initiate additional clinical studies (a Phase 2/3 study and a Phase 2 study) assessing the safety and efficacy of the drug in people living with HIV. 

Can you update on the status of Vesatolimod and Elipovimab, which are currently in early-phase clinical trials?

Ongoing Phase 1b trials in people living with HIV are evaluating safety, pharmacokinetics and pharmacodynamic effects of vesatolimod and elipovimab, including their role as part of investigational combination regimens that could potentially lead to viral remission.

Results show that vesatolimod (GS-9620) is well tolerated in people living with HIV and can induce immune activation. Additional data from studies of GS-9620 will be presented at upcoming scientific conferences next year.

Also, next year, we anticipate reporting the initial results from phase 1a and phase 1b studies evaluating elipovimab.

A pioneer HIV therapeutics, Gilead believes in finding a cure to end HIV epidemic. How soon, a cure for the epidemic can be made possible?

Curing HIV remains the ultimate long-term goal for Gilead’s HIV research and development efforts.

A multi-pronged approach will likely be needed to achieve the goal of curing HIV. The discovery and development of latency-reversing agents, immune modulators, and genetically engineered effector antibodies, as well as therapeutic vaccines with a potential for combination therapy to activate and eliminate the persistent reservoir are a current area of focus.

As we progress further with developing investigational curative regimens, our partnerships and collaborations are important. The HIV cure grants programme, initially announced in February 2016, underscores Gilead’s commitment to cure and to ultimately eradicate HIV and AIDS through its research and development and philanthropic leadership. In total, more than $29 million in grants have been awarded to academic institutions, non-profit organizations and community groups engaged in HIV cure activities.

There are still gaps in the availability of the most advanced HIV drugs to a larger section of people. Since accessibility and affordability of drugs are central to all efforts to end the epidemic, how does Gilead view the scenario?

Gilead recognizes that the development of innovative medicines for life-threatening diseases is only one aspect of improving public health. To be effective at treating disease, medicines must be available to the patients who need them. Today, it’s estimated that more than 12 million people living with HIV globally receive antiretroviral therapy provided by Gilead or one of the company’s manufacturing partners.

For more than 15 years, the company has carried out pioneering programmes and partnerships that help provide access to our medicines in low- and middle-income countries. During that time, we have learned there is no one-size-fits-all solution to treatment access challenges.

That’s why we work with public health officials, community advocates, researchers, doctors and patients to understand barriers and opportunities, with a focus on communities impacted by HIV. We apply a variety of approaches to increase disease awareness, engage partners strategically and deliver medicines efficiently.