PharmaShots Interview: ViiV Healthcare’s Kimberly Smith Shares Insights on Apretude for the Prevention of HIV

In an interview with PharmaShots, Kimberly Smith, Senior Vice President, Head of Research & Development at ViiV Healthcare shared her views on the US FDA’s approval of the first long-acting injectable option of Apretude for the prevention of HIV

The approval is based on the P-IIb/III (HPTN 083/084) trial to evaluate cabotegravir (q8w) vs FTC/TDF (200/300 mg) in 7,700+ patients who were at high risk of sexually acquiring HIV including HIV-negative men who have sex with men, transgender women & cisgender women across 13 countries
The results demonstrated superior efficacy to a daily oral PrEP option (FTC/TDF) in reducing the risk of HIV. In (HPTN 083 & HPTN 084) trial, participants who received cabotegravir experienced a lower incidence of HIV compared to FTC/TDF (69% & 90%)
Apretude is expected to be available in early 2022 in the US. The company has initiated the submissions to other regulatory authorities

Tuba: Discuss the data supporting the approval of Apretude.

Kimberly Smith: The FDA approval of Apretude is based on the results from two, international phase IIb/III multicenter, randomized, double-blind, active controlled trials, HPTN 083 and HPTN 084, which evaluated the safety and efficacy of cabotegravir long-acting for PrEP in HIV-negative men who have sex with men, transgender women, and cisgender women, who were at increased risk of sexually acquiring HIV. We’re proud that Apretude was studied in one of the most diverse and comprehensive HIV prevention trials to date, which included some of the largest numbers of transgender women and Black men who have sex with men ever enrolled in an HIV prevention trial.

In these trials, which included more than 7,700 participants across 13 countries combined, the blinded, randomized portions of both trials were stopped early by an independent Data Safety Monitoring Board after cabotegravir long-acting for PrEP was shown to be superior to daily oral emtricitabine/tenofovir disoproxil fumarate (TDF/FTC) tablets in preventing the acquisition of HIV in study participants.

Clinical trial participants who received cabotegravir long-acting for PrEP experienced a 69% lower incidence of HIV compared to FTC/TDF tablets in HPTN 083 and a 90% lower incidence of HIV compared to FTC/TDF tablets in HPTN 084.

Tuba: Please provide the understanding to our readers on the disproportionate impact of HIV on Black and Latinx communities.

Kimberly Smith: HIV continues to be a global public health crisis, with an estimated 1.2 million people in the U.S. living with HIV and approximately 37,000 new HIV diagnoses annually. However, despite new HIV cases decreasing since the peak of the epidemic, HIV continues to disproportionately impact many communities. Of the new U.S. diagnoses, men who have sex with men (MSM) and certain racial and ethnic groups are more impacted by HIV more than others:

Black and Latinx people in the U.S. make up 74% of new HIV diagnoses, despite only making up 31% of the U.S. population.
According to the CDC in 2019, the rate of new HIV diagnoses among the transgender community was approximately twenty times the national average. Of the 14% of transgender women with HIV, 70% are Black or Latinx.
Cisgender women represented 1 in 5 new HIV diagnoses in the US, 76% of which were Black or Latinx.

Tuba: Discuss the importance of the approval and its potential impact on the larger HIV community?

Kimberly Smith: The approval of Apretude, the first and only long-acting injectable option for HIV prevention, represents an exciting new option to help reduce the risk of sexually acquired HIV.

PrEP is an effective tool to reduce new cases of HIV, which in addition to successful HIV antiretroviral treatment, will help efforts to end the HIV epidemic. However, there are significant unmet needs in HIV prevention, with fewer than 25% of the 1.2 million people who could benefit from PrEP in the US currently taking it. Many people who are vulnerable to HIV have complex lives that can make taking a daily pill to prevent HIV a burden.

There is a need for new tools to help end the HIV epidemic, and long-acting medicines like Apretude, which significantly reduces the frequency of dosing from 365 days to as few as six (without the need to take a daily pill), can play a crucial role in helping to reduce new cases of HIV.

Tuba: Discuss the mechanism of action of Apretude? Explain its dosing, therapeutic efficacy, and AEs.

Kimberly Smith: Apretude is an integrase strand transfer inhibitor (INSTI). INSTIs, like cabotegravir extended-release injectable suspension, inhibit HIV replication by preventing the viral DNA from integrating into the genetic material of human immune cells (T-cells). This step is essential in the HIV replication cycle and is also responsible for establishing chronic disease.

Apretude is provided as an injection given as few as six times per year and is initiated with a single 600 mg (3-ml) injection given one month apart for two consecutive months. After the second initiation injection, the recommended continuation injection dose is a single 600 mg (3-ml) injection given every two months. Cabotegravir oral tablets may be administered for approximately one month before initiating the first injection to assess the tolerability of the medicine.

In clinical trials, the most common adverse reactions (all grades) observed in at least 1% of clinical trial participants receiving Apretude were injection site reactions, diarrhea, headache, pyrexia, fatigue, sleep disorders, nausea, dizziness, flatulence, abdominal pain, vomiting, myalgia, rash, decreased appetite, somnolence, back pain, and upper respiratory tract infection. Adverse events led to discontinuation in 6% of participants in HPTN 083 and 1% of participants in HPTN 084.

Tuba: Which locations will ViiV plan to file regulatory submissions for Apretude in 2021 and in the coming years?

Kimberly Smith: ViiV Healthcare remains committed to working collaboratively and transparently to develop new approaches that are sustainable, and relevant, address public health needs, and deliver for the people that need them. We are on track with our submissions to other Global regulatory authorities. We look forward to working closely with regulatory authorities to make this prevention option available where possible. For the latest updates on where we have submitted cabotegravir LA for PrEP please visit this page here.

Tuba: What can we expect next from ViiV’s portfolio of HIV drugs?

Kimberly Smith: As the only pharmaceutical company solely focused on HIV and AIDS, ViiV Healthcare is working to deliver a broad range of options that meet the needs of people who could benefit from PrEP as well as those living with HIV. Our broad portfolio consists of 17 antiretroviral (ARV) medicines, and we will continue to push the boundaries to make a difference in the lives of the broader HIV community. With this goal as our guide, we will continue to research long-acting medicines that allow for less frequent dosing and new medication delivery systems that provide flexibility for in-clinic or at-home administration. We will build these new medicines on the foundation of our long-acting INSTI, cabotegravir, combined with new chemical and biological candidates with unique mechanisms of action that treat HIV differently.

Source: Pexels

About Author:

Kimberly Smith is the Senior Vice President & Head of Research & Development at ViiV Healthcare. Kimberly is a graduate of the University of Michigan School of Medicine and holds an MPH degree from the University of Michigan School of Public Health. She completed her internship, residency, and Infectious Disease fellowship at Rush University Medical Center in Chicago