In an interview with PharmaShots, Dr. Kimberly Smith, Head of Global Research and Medical Strategy at ViiV Healthcare shares insights on the clinical data of GSK3640254 (GSK'254) at CROI 2021. She also highlights the key points of P-IIIb ATLAS-2M study that provide further evidence for both the once-monthly and every 2-months dosing regimens of long-acting cabotegravir and rilpivirine.

Shots:

• Results from the P-IIa POC study of GSK'254 demonstrated positive antiviral, safety, and tolerability, which showed its potential as an effective new treatment option for people living with HIV and warranted its continued study in P-IIb
• Maturation inhibitors are a unique class of antiretroviral medicines that target the late stage of the HIV viral life cycle
• Long-acting cabotegravir and rilpivirine administered every 2-months represents a shift in the way HIV is treated, offering people living with HIV a completely new approach to care

Tuba: What were the highlights of data presented by ViiV at CROI 2021?

Kimberly: ViiV Healthcare presented exciting new data from our diverse portfolio of innovative pipelines and licensed HIV treatment and prevention options at CROI 2021. The most notable of these presentations included updates that demonstrated the potential of new antiretroviral mechanisms of action alongside our long-acting medicines that challenge the HIV treatment and prevention paradigm.

Our 96-week data from the ATLAS-2M study demonstrated long-term efficacy and safety for the investigational regimen of long-acting cabotegravir and rilpivirine administered every 2-months that further reinforced its therapeutic potential. Additionally, findings from our phase IIa proof-of-concept study of the maturation inhibitor GSK'254 demonstrated positive antiviral, safety, and tolerability, which showed its potential as an effective new treatment option for people living with HIV and warranted its continued study in phase IIb.

Tuba: How will the findings from the presentation of long-acting therapies and POC data help the HIV community?

Kimberly: At ViiV Healthcare, we're driven to redefine what is possible in how we prevent, treat, and manage HIV. A key component of this approach involves developing therapies that challenge the existing treatment and prevention paradigm while also leaving no person living with HIV behind. The findings that we presented at CROI 2021 reflect these two aims. There are new long-term data that further establish long-acting therapy, which can allow people living with HIV the ability to reduce treatment days from 365 to 12 or 6 per year to new proof-of-concept data in maturation inhibitors that speak to the potential of new mechanisms of action in our efforts to end this epidemic.

Tuba: Discuss the key findings of the P-IIa POC study assessing GSK3640254 (GSK'254) at CROI 2021.

Kimberly: These positive proof-of-concept findings show the potential of GSK'254 and underscore our commitment to researching and developing a broad range of innovative approaches to treating HIV.

The phase IIa proof-of-concept study demonstrated the antiviral activity, safety, and tolerability of GSK'254 and established a relationship between dose and antiviral response, with the 140 mg and 200 mg doses demonstrating the greatest reduction in plasma HIV-1 RNA. The findings also demonstrated that treatment with GSK'254 was generally well-tolerated throughout the study, with no adverse events leading to discontinuation.

We-re looking forward to the next step in our study of GSK'254, which will involve a phase IIb study that evaluates the efficacy, safety, and tolerability of the maturation inhibitor as part of combination therapy for treatment naïve adults living with HIV.

Tuba: Can you shed some light on Maturation inhibitors? How do they help in treating HIV?

Kimberly: Maturation inhibitors are a unique class of antiretroviral medicines that target the late stage of the HIV viral life cycle. They can prevent the HIV replication process by blocking key enzyme activity at this stage, which results in the formation of immature virus particles that are non-infectious. Because maturation inhibitors use a unique mechanism of action that targets HIV differently than other antiretrovirals currently available, they have the potential to offer new treatment options for individuals who may have experienced resistance to other classes of HIV treatment.

HIV has the potential to develop resistance to treatment over time. This makes it not uncommon for individuals to experience a treatment failure over the course of their life experience with HIV. Thus there is a need to research and advance medicines that use new mechanisms of action so that we can increase the treatment options that are available for people living with HIV. The antiviral, safety and tolerability findings observed in this proof-of-concept study show the potential of this maturation inhibitor as an effective new treatment option for people living with HIV and warrant its continued study.

Tuba: Can we have a in depth discussion of long-term efficacy and safety data from the P-IIIb ATLAS-2M study?

Kimberly: The 96-week findings from the phase IIIb ATLAS-2M study reinforce the therapeutic potential of long-acting cabotegravir and rilpivirine every 2-months for the treatment of HIV. It provides an option that could change the treatment experience for some people living with HIV by removing the need for daily pills for the treatment of HIV.

The Week 96 findings reinforced the primary endpoint from ATLAS-2M, in which the efficacy of every 2-month dosing was non-inferior to monthly dosing of long-acting cabotegravir and rilpivirine, with 2.1% (11/522) and 1.1% (6/523) of participants, respectively, having HIV-1 RNA =50 c/mL. The secondary endpoint of the 96-week ATLAS-2M study showed that rates of virologic suppression were similar between the two arms, with 91.0% of participants in the every 2-month dosing arm and 90.2% in the monthly dosing arm.

The study showed similar safety profiles between every 2-month and monthly dosing, with no new safety signals identified since the 48-week analysis.

Tuba: How can the every 2-month dosing regimen of cabotegravir and rilpivirine change the treatment experience for some people living with HIV? Do you think compliance will improve?

Kimberly: Long-acting cabotegravir and rilpivirine administered every 2-months represents a shift in the way HIV is treated, offering people living with HIV a completely new approach to care. The reality is that there is an unmet need for long-acting treatment options that can offer the convenience of reduced dosing days. Additionally, taking a pill every day can come as an unwelcome daily reminder of their HIV status or it may add to their fears that their HIV status might be disclosed by someone seeing their HIV medication. This regimen can enable people living with HIV to reduce the days they receive treatment from 365 to 12 or 6 per year, representing a paradigm shift in their experience of HIV treatment.

Tuba: What would be the targeted geographies for seeking approval for the every 2-month dosing regimen of cabotegravir and rilpivirine?

Kimberly: The long-acting regimen of cabotegravir and rilpivirine is licensed as a once-monthly treatment in Canada and the US under the brand name Cabenuva. A supplemental New Drug Application has been submitted to the US Food and Drug Administration for expanding the use of Cabenuva as an HIV treatment to include every 2-month dosing in the US. Cabenuva is listed in Australia for both monthly and every 2-month dosing. The long-acting regimen has also received Marketing Authorisation under the brand names Vocabria (cabotegravir) and Rekambys (rilpivirine) in Europe for both monthly dosing and every 2-month dosing. Further regulatory applications have been submitted and are being reviewed by other regulatory bodies worldwide.

About Author:

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.

Related Post: PharmaShots Interview: Leap Therapeutic's Douglas Onsi Shares Insight on its Lead Candidate, DKN-01