121: Monoclonal Antibodies for Treatment & Prevention of Infectious Diseases: An Overview of Clinical Pharmacology Contributions & Opportunities

Statement of Purpose: Monoclonal antibodies (mAbs) can treat and prevent viral infections through preventing viruses from binding to the target host cells. The mAbs approved against bacteria mainly target bacterial exotoxins to inhibit the interaction between the toxin and its receptor.
The following mAbs are approved for treatment or prevention of infectious diseases: palivizumab, raxibacumab and obiltoxaximab, bezlotoxumab, Ibalizumab, atoltivimab/odesivimab/maftivimab and ansuvimab.
Palivizumab is approved for prevention of the respiratory syncytial virus (RSV) in pediatric patients at high risk, raxibacumab and obiltoxaximab are approved for treatment and prophylaxis of inhalational anthrax and the bezlotoxumab was used for prevention of Clostridium difficile infection recurrence. Ibalizumab was approved for treatment of HIV-1 infection in heavily treatment experienced adults with multidrug resistant HIV-1 infection. Atoltivimab/odesivimab/maftivimab and ansuvimab were approved for treatment of infection caused by Zaire ebolavirus. Several neutralizing mAbs that target severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were authorized under emergency use. Efforts are being made to develop mAbs for preventing parasitic infections such as Plasmodium falciparum.
This study is aimed to summarize information (such as mechanism of action and target) of mAbs, highlight the impact of clinical pharmacology, and identify opportunities to facilitate the development of mAbs for preventing and treating infectious diseases.

Description of Methods & Materials: A literature search using the key words “monoclonal antibodies for infectious diseases” and “monoclonal antibodies antibacterial and antiviral diseases” was conducted. Information related to approved biological license applications (BLAs) and drug labels from drugs@FDA was extracted. Information for drugs authorized under emergency use was obtained from CDER scientific review documents supporting emergency use authorizations (https://www.fda.gov/drugs/coronavirus-covid-19-drugs/cder-scientific-review-documents-supporting-emergency-use-authorizations-drug-and-biological).

Data & Results: As of April 6, 2023, seven mAbs targeting pathogens have been approved by the FDA for treatment and/or prevention of infectious diseases.
Raxibacumab and obiltoxaximab were approved under the US FDA Animal Rule for prevention and treatment of inhalational anthrax.
The following mAbs targeted against SARS-CoV-2 were previously authorized for emergency use: bamlanivimab/etesevimab, casirivimab/imdevimab, bebtelovimab, sotrovimab, cilgavimab/tixagevimab.
Contribution of clinical pharmacology was significant for the development of drugs for infectious diseases in following areas:
a) Dose selection for patients or optimizing dosing regimens
b) Dose evaluation in response to new variants as reduction in susceptibility have been observed for mAbs against SARS-CoV-2
c) Use in different specific populations
Half-life enhancing YTE mutations in the Fc region of the mAbs to extend half-life presents a unique opportunity for dose optimization of mAbs.

Interpretation, Conclusion or Significance: Recent progress in mAbs development against infectious diseases show that mAbs have demonstrated utility for treatment and prevention of infectious diseases. Extended half-lives of mAbs may allow less frequent dosing. Further, mAbs have less drug-drug interaction concerns. Clinical pharmacology can play a vital role to facilitate the development of mAbs for the prevention and treatment of infectious diseases.

Disclosures: NO