Designing and implementing clinical studies of monoclonal antibodies
for HIV and SARS-CoV-2: What have we learned to date?
Rapporteur: Trip Gulick, Rapporteur for Focus Group 3
Summarized the discussion concerning development of monoclonal antibodies (mAb) for prevention and treatment of HIV and SARS-CoV-2. Discussion leaders, Katie Bar (University of Pennsylvania) and Marina Caskey (Rockefeller University), structured the session by considering each virus separately and discussing the advantages and disadvantages.
Advantages of HIV mAbs.
HIV mAbs have potent antiviral activity. Clinical experience exists with HIV treatment (pilot data) and prevention (Phase 2/3), and many studies are underway. HIV mAbs are generally safe and well-tolerated, have long half-lives and low potential for DDIs. Target concentrations are rapidly reached with IV administration, and there is potential for SC dosing. Reducing the size of the HIV reservoir (a step towards HIV cure) is a theoretical benefit.
Disadvantages of HIV mAbs.
Current standard of care for HIV treatment and prevention are excellent. Main challenge for mAbs is resistance due to changing HIV envelope diversity, which will require monitoring of circulating strains (HIV prevention) and standardized resistance testing (HIV treatment). CNS penetration of mAbs is low, and high target concentrations are needed for prevention. Data are lacking among special populations. Use is also complicated by the cold chain requirement, the need for community education and high cost, particularly for LMICs.
Advantages of SARS-CoV-2 mAbs.
Current standard of care for outpatients is limited to supportive treatment – there is a unique opportunity. Can leverage the experience with HIV. SARS-CoV-2 mAbs demonstrate virologic activity (more potent in combination vs. monotherapy) – in Phase 2/3 studies of high-risk patients, monotherapy and combinations can prevent hospitalization and death, and emerging data for prevention show decreases in transmission in nursing homes and among household contacts. Generally well-tolerated, have a long half-life, and target concentrations are rapidly achieved with IV administration. Administered as a single IV infusion for treatment or prevention, and other modalities are being studied (SC, IM, inhaled).
Disadvantages of SARS-CoV-2 mAbs.
Resistance of certain epitopes is the main concern. Vaccines are the current SOC for prevention. Immunocompromised hosts could benefit, but also have prolonged viral excretion and could select resistance. Data are lacking among special populations, and use in people with active SARS-COV-2 infection is complicated by infection control issues, the need for community education and high cost (prohibitive in LMICs).
Next steps in development of mAbs for HIV and SARS-Cov-2.
1) Develop combination regimens for HIV (e.g., HIV mAb administered in combination with ART).
2) Studies of LA IV and SC formulations for HIV with every 6 month to 12 month dosing and additional formulations for SARS-CoV-2 mAbs (SC, IM and inhaled).
3) Novel HIV cure studies.
4) Studies in children and pregnant/breastfeeding women (HIV and SARS-CoV-2) and immunocompromised populations (SARS-CoV-2).