The biologic is composed of three monoclonal antibodies (mAbs) directed against the Ebola Zaire virus strain, drawn from MB-003 and ZMab. The antibodies were licensed from Defyrus and the US Army Medical Research Institute of Infectious Diseases (USAMRIID) to Mapp’s commercialisation arm LeafBio after an agreement formed in July 2014.
Under the terms, ZMapp antibodies are being produced for LeafBio by Kentucky Bioprocessing (KBP), a firm which produces plant-based proteins in a way – it claims – is faster and more easily scalable than bioreactor-based methods.
The company is humanising manufacturing the ZMapp antibodies in tobacco variety Nicotiana benthamiana. Mapp said Icon Genetics AG (Halle, Germany) had also been “vital” to the process by pioneering the vectors for engineering Nicotiana to produce biopharmaceuticals.
Exhausted supplies, experimental use
Mapp is under pressure to produce more of the biologic, and fast, after announcing on August 12 that its supply had been exhausted after donating its scant stores to patients.
“We have complied with every request for ZMapp that had the necessary legal/regulatory authorization,” said the company, adding “it is the requestors’ decision whether they wish to make public their request, acquisition, or use of the experimental drug.”
The drug was in its preclinical stages when the West Africa Ebola virus outbreak was detected in March 2014. Although not approved for human use by the US Food and Drug Administration (FDA), it was donated by ZMapp (via the FDA and an NGO) to seven known patients infected in Liberia, Monrovia and Sierra Leona.
Animal tests show promise, as a paper published last month in Nature claims ZMapp prompted reversion of advanced Ebola in nonhuman primates.
The FDA can authorise – not “approve” – use of an early-stage drug in emergencies such as the Ebola outbreak through its Expanded Access (“compassionate use”) pathway by creating an early IND (investigational new drug) application.
The agency said it cannot reveal which compounds have been subject to IND submissions, but said if an experimental treatment were to be administered in the US, an emergency IND application would have to be authorised by the FDA.
The first patients to receive ZMapp, two American health workers in Liberia, were transported to the US and released from hospital on August 21. Miguel Pajares, a priest infected in Monrovia, and Abraham Borbor, a Liberian doctor, both died last month despite receiving ZMapp.
Two other Liberian doctors and a British nurse infected in Sierra Leone have been treated with the experimental biologic.