Bavituximab

Bavituximab (PGN401) is a human-mouse chimeric monoclonal antibody against phosphatidylserine, which is a component of cell membranes that is exposed when a cell is transformed into solid tumor cancer cell or dies,[1][2] and when cells are infected with hepatitis C.[3] The process of cell death is highly controlled and so there usually no immune response to phosphatidylserine but when bavituximab binds to it, the conjugate appears to stimulate an immune response in humans.[2]

Bavituximab
Monoclonal antibody
TypeWhole antibody
SourceChimeric (mouse/human)
Targetphosphatidylserine
Clinical data
Routes of
administration		infusion
ATC code
  • none
Pharmacokinetic data
Elimination half-life30 hrs
Identifiers
CAS Number
ChemSpider
  • none
UNII
Chemical and physical data
FormulaC6446H9946N1702O2042S42
Molar mass145304.87 g·mol−1
  (verify)

Biology

Phosphatidylserine is the most abundant anionic phospholipid in the cell's plasma membrane, and is usually positioned internally. However, during apoptosis and several pathological conditions including tumorigenesis or infection by some types of viruses, phosphatidylserine is flipped from an internal to an external position.[4] When external, it can potentially be recognized by antibodies. As such, targeting external phosphatidylserine may be a strategy for novel broad-spectrum anti-viral therapies.[5] Bavituximab is an antibody that binds to complexes of the phosphatidylserine-binding plasma protein β2-glycoprotein 1 and anionic phospholipids. In laboratory experiments, treatment with bavituximab was found to rescue mice from otherwise lethal infections of mouse cytomegalovirus (CMV), and Pichinde virus, a model of Lassa fever virus. Proposed mechanisms for this therapeutic effect included bavituximab directly clearing infectious virus from the bloodstream, and the induction of antibody-dependent cellular cytotoxicity of virus-infected cells. [4][5]

Bavituximab inhibited replication of influenza in preliminary experiments in chicken eggs.[6]

History

Bavituximab was invented at University of Texas Southwestern Medical Center at Dallas; Peregrine Pharmaceuticals exclusively licensed intellectual property related to bavituximab from the university, including US patent 6,300,308 invented by Alan J. Schroit and US Patents 6,406,693 and 6,312,694 invented in the laboratory Philip E. Thorpe.[7]: 6 [8]

As of January 2016, bavituximab had been in a Phase III clinical trial for non-small cell lung cancer (NSCLC),[9] a Phase II/III trial for breast cancer, a Phase II trial for pancreatic cancer, a phase I/II trial for hepatocellular carcinoma, and Phase I clinical trials in malignant melanoma and rectal cancer; its development had been discontinued for influenza and prostate cancer.[1] As of 2011 it had been in a Phase II trial for hepatitis C[3] but no results had been reported as of 2016.[1]

The phase III (SUNRISE) trial for NSCLC was discontinued in early 2016 after analysis of interim results.[10]

Peregrine changed its business focus to contract manufacturing and changed its name to Avid Bioservices at the end of 2017, and in February 2018 it sold bavituximab and its other drug assets to Oncologie Inc.[11][12]

References
  1. Staff, Adis Insight. Bavituximab profile Last updated Jan 27 2016
  2. Mahoney KM, Rennert PD, Freeman GJ (August 2015). "Combination cancer immunotherapy and new immunomodulatory targets". Nature Reviews. Drug Discovery. 14 (8): 561–84. doi:10.1038/nrd4591. PMID 26228759. S2CID 2220735.
  3. Ahn J, Flamm SL (August 2011). "Hepatitis C therapy: other players in the game". Clinics in Liver Disease. 15 (3): 641–56. doi:10.1016/j.cld.2011.05.008. PMID 21867942.
  4. Soares, M. Melina; King, Steven W.; Thorpe, Philip E. (23 November 2008). "Targeting inside-out phosphatidylserine as a therapeutic strategy for viral diseases". Nature Medicine. 14 (12): 1357–1362. doi:10.1038/nm.1885. PMC 2597367. PMID 19029986.
  5. Tse, Man Tsuey; King, Steven W; Thorpe, Philip E (January 2009). "Exposed target for broad-spectrum antivirals". Nature Reviews Drug Discovery. 8 (1): 19. doi:10.1038/nrd2788. S2CID 19531326.
  6. "Peregrine Pharmaceuticals' Bavituximab Shows Potential Activity Against Avian Flu In Initial Testing". 24 May 2006. Retrieved 26 April 2020.
  7. Peregrine's Annual Report for the fiscal year ended April 30, 2015
  8. Peregrine press release: Peregrine Pharmaceuticals Licenses Additional Intellectual Property for Its Anti-Phospholipid Therapy Platform Technology Archived 2016-02-16 at the Wayback Machine. July 6, 2004
  9. Phase 3 Study of Bavituximab Plus Docetaxel Versus Docetaxel Alone in Patients With Late-stage Non-squamous Non-small-cell Lung Cancer (SUNRISE)
  10. Inman S (February 26, 2016). "Peregrine Stops Phase III Trial of Bavituximab in NSCLC". OncLive.
  11. Brennan PJ (December 26, 2017). "Peregrine Names CEO, to Change Name". Orange County Business Journal.
  12. Elvidge S (February 13, 2018). "Avid sells off cancer assets, transitioning to CDMO". BioPharma Dive.
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