Johnson & Johnson Announces Encouraging First-in-Human Clinical Data for Investigational HIV Preventive Vaccine

Johnson & Johnson announced encouraging first-in-human clinical data for an investigational HIV-1 vaccine regimen in development at its Janssen Pharmaceutical Companies. In an oral presentation of the early stage Phase 1/2a APPROACH study at the 9th IAS Conference on HIV Science (IAS 2017), the "mosaic"-based vaccine regimen from Janssen Vaccines & Prevention B.V. (Janssen) appeared to be well-tolerated and elicited HIV-1 antibody responses in 100 percent of healthy volunteers (n=393).

"Finding a preventive vaccine has proven to be one of the biggest scientific challenges in the 35-year quest to end the HIV pandemic. A successful preventive vaccine for HIV will need to provide broad protection against a wide range of viral strains," said Professor Dan Barouch, Harvard Medical School, Director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center and a key collaborator for APPROACH. "These promising, early-stage results suggest that these vaccines utilizing mosaic immunogens should be evaluated further for their potential ability to achieve this historic goal."

Significant progress has been made in the global battle against HIV/AIDS, including the development of critical antiretroviral treatments and HIV prevention tools, yet the disease remains one of the greatest global health threats of our time. An estimated 37 million people are currently living with HIV-1 globally, and nearly 2 million people become newly infected each year. An effective HIV vaccine is elusive due to the unique properties of the virus -- including its genetic diversity and ability to mutate rapidly.

Mosaic-based vaccines contain immunogens created using genes from different HIV subtypes responsible for HIV-1 infections worldwide. These immunogens are delivered through viral vectors, including Janssen's AdVac� technology based on adenovirus serotype 26 (Ad26). The viral vectors are combined with other components such as soluble proteins to form mosaic-based prime-boost vaccine regimens that first prime and then boost the immune system, with the aim of producing stronger and longer-lasting immunity to HIV.

Paul Stoffels, M.D., Chief Scientific Officer, Johnson & Johnson said, "In recent years, a new optimism has emerged that we will find an effective HIV vaccine in our lifetime. The results from today's study add to that belief, and we look forward to advancing to the next stage of clinical development as quickly as possible."

In pre-clinical studies, regimens incorporating mosaic vaccines demonstrated protection against infection with an HIV-like virus. The most effective prime-boost regimen in these studies reduced the per-exposure risk of infection by 94 percent and resulted in 66 percent complete protection after six exposures.

Based on immunologic responses observed in APPROACH, as well as protection observed in pre-clinical studies, a lead HIV-1 vaccine regimen comprising Janssen's Ad26 mosaic candidate and the Clade C gp140 soluble protein has been selected as the basis for further evaluation in a potential Phase 2b proof-of-concept efficacy study. Should this study move forward, Janssen and its global partners anticipate initiating this investigation in southern African countries in late 2017 or early 2018.

APPROACH (HIV-V-A004/NCT02315703) is a multicenter, randomized, parallel-group, placebo-controlled, double-blind Phase 1/2a study in 393 healthy HIV-uninfected adults in the US, Rwanda, Uganda, South Africa and Thailand. It is evaluating the safety, tolerability, and immunogenicity of various mosaic-based, prime-boost vaccine regimens for HIV-1. These vaccine regimens contain two prime doses of the mosaic viral vector Ad26.Mos.HIV and two boosts of either Ad26.Mos.HIV, MVA-Mosaic and/or different doses of the soluble protein Clade C gp140 adjuvanted with aluminum phosphate. Vaccination schedules have been completed for all study participants and 12-month follow-up after the 4th dose is underway.

Results presented at IAS 2017 suggest that all vaccine regimens appeared to be well-tolerated. Injection site pain, headache, and fatigue were the most common reported adverse events. The primary analysis post 3rd vaccination showed that most active vaccine regimens elicited antibody responses in 100% of study participants. Antibody titers against autologous Clade C and heterologous cross-clade Env antigens increased in groups boosted with gp140 protein, irrespective of vector. After the 4th vaccination, humoral and cellular responses further increased.

The APPROACH study was sponsored by Janssen with support from partner organizations including Beth Israel Deaconess Medical Center (BIDMC); the United States Military HIV Research Program (MHRP) at the Walter Reed Army Institute of Research (WRAIR), with the Henry M. Jackson Foundation for the Advancement of Military Medicine (HJF); the National Institute of Allergy and Infectious Diseases (NIAID), part of the US National Institutes of Health (NIH); the Ragon Institute; the International AIDS Vaccine Initiative (IAVI); and the HIV Vaccine Trials Network (HVTN).

Janssen's HIV-1 AdVac�-based vaccine regimen, along with the company's investigational Ebola and inactivated polio vaccine candidates, utilize Janssen's PER.C6� production cell line technology, which has the potential to reduce costs by increasing vaccine production at lower reactor volume.

Since 2005, Janssen Vaccines & Prevention B.V. has been participating in the NIH-supported Integrated Preclinical/Clinical AIDS Vaccine Development (IPCAVD) program under grants AI066305, AI078526 and AI096040. Janssen's HIV vaccine program has also received funding from the United States Military HIV Research Program and the Ragon Institute.

For more information, visit www.jnj.com/HIV