In an interview with PharmaShots, Dr. Kimberly Smith, Head of Research & Development, ViiV Healthcare shed light on the FDA’s approval and the 3yrs. data of Dovato.
- Dovato (dolutegravir/lamivudine) is the first complete, once-daily, single-tablet, 2DR for the treatment of HIV-1 infection in both treatment-naïve and virologically suppressed adults
- In Aug 2020, the FDA approved an expanded indication for Dovato virologically suppressed adults with HIV-1 who are on a stable ARV regimen and have no prior treatment failure or known resistance to the components of Dovato
- Three-year data strengthen the long-term evidence of Dovato as it continued to offer non-inferior efficacy, a high genetic barrier to resistance, and a comparable safety profile vs a 3-drug regimen of dolutegravir plus tenofovir disoproxil fumarate/emtricitabine (TDF/FTC)
Tuba: Could you please share how Dovato will help patients living with HIV who are on medications for decades?
Dr. Smith: Dovato is a noteworthy medication because it is a complete single-tablet HIV regimen that contains only two drugs. Typically, the standard of care for HIV treatment has required a combination of three or more antiretroviral (ARV) therapies, but at ViiV Healthcare, we’ve challenged this paradigm, believing that no person living with HIV should take more medications than they need.
As a complete two-drug regimen (2DR), Dovato provides people living with HIV a treatment that reduces the number of ARV therapies they take, while maintaining efficacy and a high barrier to resistance comparable to tenofovir-based regimens of at least three drugs. Now that HIV is a manageable condition that requires lifelong treatment, we’ve heard from the community that taking fewer medications over the long-term is an important consideration so Dovato is a valuable option for many patients.
Tuba: Can we have a glimpse of Dovato’s data presented at the HIV Glasgow 2020 congress?
Dr. Smith: HIV Glasgow was an important congress for us because we were able to present new long-term data from two pivotal trials (GEMINI 1 & 2 and TANGO) which confirmed Dovato’s well-established efficacy, safety, and tolerability profile. Highlights of the presented results include:
- We shared three-year results from the GEMINI 1 & 2 studies, which showed Dovato continued to provide non-inferior efficacy, a high genetic barrier to resistance, and a comparable safety profile versus a three-drug regimen in treatment-naïve adults living with HIV.
- We also shared 96-week data from the TANGO study where Dovato continued to demonstrate non-inferior efficacy in virologically suppressed adults with HIV who have not previously experienced virologic failure. No participants on Dovato met protocol-defined virologic failure.
- Dovato is a well-tolerated medication, and in both GEMINI and TANGO trials, the safety results were consistent with the product labeling for dolutegravir and lamivudine.
The data presented continue to build upon the momentum behind 2DRs – Dovato has now shown sustained efficacy and tolerability through three years of treatment, with people able to maintain viral suppression with fewer ARVs than a 3-drug regimen.
Tuba: Can we have a discussion about how Dovato’s mechanism of action is different from Biktarvy?
Dr. Smith: Unlike Biktarvy, a complete regimen containing three drugs, Dovato is a complete regimen that is comprised of only two drugs, dolutegravir and lamivudine.
Dovato, powered by dolutegravir at the core, is an integrase strand transfer inhibitor which works to block HIV replication by preventing the viral DNA from integrating into the genetic material of human immune cells. This step is essential in the HIV replication cycle and is also responsible for establishing chronic infection. Lamivudine is a nucleoside reverse transcriptase inhibitor which blocks the enzyme reverse transcriptase and helps slow the progression of HIV by limiting the virus’s ability to replicate.
Tuba: The US FDA has approved an expanded indication for Dovato (dolutegravir/lamivudine). What were the milestones that led to this approval?
Dr. Smith: This August, the FDA approved an expanded indication for Dovato for use in virologically suppressed adults living with HIV who are on a stable ARV regimen and have no prior treatment failure and no known resistance to the individual components of Dovato. The treatment was approved as a complete regimen to replace the current ARV regimen.
The expanded indication is based on the Week 48 results from the phase III TANGO study. The TANGO data are the first evidence from a clinical trial to show that the 2DR Dovato is comparable to a TAF-containing regimen of at least three drugs in virally suppressed adults with HIV. Through 48 weeks, no participants on Dovato and one participant (<1%) on the TAF-containing regimen met confirmed virologic failure criteria, with no resistance mutations observed at failure. The safety results for those who switched to Dovato were consistent with the product labeling for dolutegravir and lamivudine. Across the phase III TANGO study, the most common side effects reported by ≥1% of patients in either treatment group through 48 weeks were trouble sleeping (2%), nausea (1%), diarrhea (1%), and anxiety (1%).
We were thrilled that this trial was able to confirm that a 2DR can maintain viral suppression as effectively as a TAF-containing regimen and led to the expanded indication for Dovato, making it available to even more people living with HIV.
It’s important to note that we now have longer-term 96-week data from the TANGO study that shows Dovato maintains these positive safety and efficacy results.
Tuba: Which companies does ViiV think are potential threats to their HIV therapies especially Dovato?
Dr. Smith: ViiV Healthcare is the only pharmaceutical company that’s solely dedicated to HIV. Our singular focus enables us to research and deliver innovative HIV medicines and solutions that deliver on our mission to leave no person living with HIV behind.
It’s this mission that led us to be the architect of the 2DR era. We know the number of people living with HIV living normal lifespans is increasing, and that’s testament to the success of ARV therapy, which has transformed HIV into a chronic condition. However, living longer with HIV can mean taking multiple medications for many years. People don’t want to take more medicines than they need to manage their HIV.
We are leading the industry in bringing these new regimens to patients. Because of our success, 2DRs are gaining momentum in the treatment landscape and now other companies are starting to follow suit and invest in the development of 2DR regimens.
Tuba: Is ViiV working on any digital plan to eradicate HIV globally?
Dr. Smith: The digital technologies that exist today are incredibly powerful tools that allow us to connect with HIV communities that previously would have been beyond our reach. We offer a number of digital resources for the HIV community and healthcare providers to encourage discussion about effective HIV care, including LiVLife, our website for people living with HIV in the UK; Positively Thriving, our podcast series by and for people living with HIV in the UK; Being Seen, our podcast inspired by the stories and experiences of Black gay and queer men in the US; and the Positive Perspectives policy manifesto, which provides recommendations for empowering people living with HIV to move from surviving to thriving with HIV.
But ending HIV goes beyond our digital plans. Our efforts to eradicate HIV are centered around our collaboration with the University of North Carolina (UNC) at Chapel Hill. In March 2020, ViiV announced a five-year, $20 million renewal of this unique, public-private research partnership, solely focused on discovering a cure for HIV. Since its inception in 2015, this collaboration, the first-of-its-kind in the field of HIV cure, has brought together the skills of academic and pharmaceutical industry researchers to create a deeper understanding of how HIV works and develop a new approach to eradicating HIV that could be tested in humans for the first time in the next few years. Our work with UNC is part of a holistic approach that spans education, prevention and access efforts.
We’ll continue to develop these partnerships and digital initiatives that advance our mission of eradicating HIV once and for all.
Tuba: Can we have a quick highlight of ViiV’s HIV portfolio?
Dr. Smith: We’re really proud of our broad portfolio in the US, which includes 14 HIV medications in six ARV drug classes and offers a range of options for people living with HIV. Our research and development programs take a patient-centered approach to innovation and the progress we’ve made clearly underscores our focus on leaving no person living with HIV behind. Over the past few years, our portfolio has grown significantly, and we’ve achieved meaningful progress for the HIV community through these approvals:
- In 2019, we launched Dovato as the first, once-daily, single-tablet, 2DR for treatment-naïve adults living with HIV. In August of 2020, we received an expanded indication for Dovato, extending its use to virologically suppressed adults living with HIV who are on a stable ARV regimen and have no prior treatment failure and no known resistance to the individual components of Dovato and who want to reduce the number of drugs they are exposed to each day.
- In June 2020, the FDA approved Tivicay PD, the first-ever dispersible tablet formulation of dolutegravir and a once-daily treatment for children living with HIV in combination with other ARVs for the treatment of HIV-1 infection in integrase strand transfer inhibitor (INSTI)-naive pediatric patients at least 4 weeks old and weighing at least 3 kg. Tivicay PD addresses an unmet treatment need in this vulnerable population by providing an age appropriate formulation of dolutegravir for children.
- In July 2020, the FDA approved Rukobia (fostemsavir), an attachment inhibitor for the treatment of HIV-1 infection indicated for use in combination with other ARV therapies in heavily treatment-experienced (HTE) adults with multidrug-resistant HIV-1 infection, who are failing their current ARV regimen due to resistance, intolerance or safety considerations. Many HTE adults have few options left and are greater risk of disease progression.
- In January 2021, the FDA approved Cabenuva (cabotegravir, rilpivirine), the first and only complete long-acting regimen for the treatment of HIV-1 infection in adults on a stable regimen, with no history of treatment failure, and with no known or suspected resistance to either cabotegravir or rilpivirine. Cabenuva is provided as a co-pack with two injectable medicines, ViiV’s cabotegravir and Janssen’s rilpivirine,dosed once monthly to replace the current ARV regimen, offering a new treatment option that maintains viral suppression with 12 dosing days per year.
Tuba: After the US, EU, Japan, which are the other geographical areas in focus for seeking approval of Dovato?
Dr. Smith: Since Dovato was first approved in 2019 in the US, it is now available in a number of countries around the world including Canada, Australia, the UK, many countries in the EU, Japan and Korea. Additional regulatory applications for Dovato have been submitted in several other markets.
Tuba: What specifically do you want to discuss about Dovato to our readers/ subscribers?
Dr. Smith: The scientific community has made amazing advancements in HIV care during the last few decades, and now that we have several effective ARV therapies to treat HIV, we are able to shift our focus to address other treatment considerations like tolerability and long-term effects of HIV medicine. That idea is at the heart of our 2DR strategy.
We’ve made great strides here, with Dovato now included in both US and EU ARV treatment guidelines. The progress we’ve made around 2DRs underscores the important role they will continue to have in the HIV treatment paradigm, offering people living with HIV a way to suppress their virus while reducing the number of ARVs taken per day.
Beyond Dovato, we are looking forward to another great year of progress ahead; we won’t stop until our research offers more ways to treat, prevent and hopefully one day cure, HIV.
Image Source: Grupo Gamma
Dr. Kimberly Smith is a Head of Research & Development at ViiV Healthcare. Dr. Smith has made eradicating HIV her life’s work. After starting her career treating AIDS patients in Chicago early in the epidemic, Dr. Smith is now one of the first women of color to lead research and development for a multi-national pharmaceutical company