Issue link: https://www.e-digitaleditions.com/i/1300450
4 BioPharm International eBook October 2020 www.biopharminternational.com u l o c y t e m a c r o p h a g e - c o l o n y s t i mu l at i n g f a c t o r (G M – C S F ) m o n o c lo n a l a nt i b o d y (m A b), which has the potential to be a first-line treatment. The company expects that it may improve the time of recovery for a COVID-19- afflicted patient and may prevent serious and potentially fatal out- comes in hospitalized patients. The candidate is in Phase III clin- ical development in the United States, Brazil, and Mexico. In early October 2020, FDA gave favor- able feedback that the company's submission for the biologic to be ut i l i zed u nder E mergenc y Use Authorization (EUA) may be suffi- cient to support that request (4). Hu ma n igen for med col labo - rations in September 2020 with contract development and manu- facturing organizations (CDMOs) Thermo Fisher Scientific (5) and Lonza (6) to expand manufacturing of lenzilumab. Under the Thermo Fisher col laborat ion, com mer- cial-scale manufacturing can poten- tially commence before the end of this year following the technical transfer of the lenzilumab bulk drug substance process. With the Lonza collaboration, technology transfer is expected to start in the third quarter of 2020, with current good manufac- turing practice (CGMP) production expected to start up in 2021 at Lonza's 2000-L manufacturing facil- ities in Hayward, CA. Humanigen is also partnered with Catalent, who is providing development, manufacturing, and commercia lizat ion ser v ices for lenzilumab (7). Catalent Biologics has supported Humanigen's clini- cal trials by conducting early-stage development and clinical CGMP drug substance manufacturing of lenzilumab at its Madison, WI, facil- ity. Catalent is also providing drug substance clinical supply for clini- cal trials and will provide late-stage development as well as clinical and potential commercial drug substance manufacturing and vial filling at its Bloomington, IN, site and at its Madison facility. Separately, Humanigen has a fill/ finish supply agreement with CDMO Ajinomoto Bio-Pharma Services (8) for lenzilumab. The CDMO will pro- vide drug product aseptic fill/finish services at its San Diego, CA, facility. Siltuximab Eusa Pharma, a biopharmaceutical company, is conducting studies on siltuximab, a chimeric mAb that tar- gets human interleukin-6, for use as a potential COVID-19 treatment. The study (SISCO), sponsored by Papa Giovanni XXIII Hospital in Lombardy, Italy, is exploring use of the mAb to treat serious respiratory complications in patients who have contracted COVID-19 (9). Interim data analyzed in late March 2020 showed that 33% of hospitalized patients showed a clinical improve- ment and that the condition of 43% of patients stabilized when adminis- tered the therapy (10). In July 2020, FDA approved a Phase III clinical trial protocol from Eusa to conduct a study in hospital- ized patients in the United States; siltuximab will be combined with the hospital-based standard of care to treat patients exhibiting COVID- 19 -associated acute respiratory dis- tress syndrome (ARDS) (11). FDA, the European Medicines Agency (EMA), and other regulatory bod- ies in other worldwide jurisdictions have approved siltuximab (marketed under the brand name Sylvant) for treating multicentric Castleman disease in patients who are human immunodeficiency virus negative and human herpesvirus-8 negative. NEUTRALIZING ANTIBODIES Work is also underway to develop neutralizing antibodies that can directly attack the SARS-CoV-2 virus itself. Biopharma companies Eli Lilly and Company (Lilly) and Amgen are pursuing this route. Lilly's investigational antibody product, LY- CoV555 (developed from a collaboration between Lilly and AbCellera), was generated just three months after being identified from a blood sample taken from a US patient who caught the virus early on and recovered. AbCellera and the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases identified the antibody (12). LY-CoV555, a neutralizing immunoglobulin G1 (IgG1) mAb that targets the spike protein of SARS-CoV-2, can block viral attachment, thus keeping the virus from entering human cells (i.e., "neutralizing" it). It is expected that the mAb can potentially pre- vent infection and treat COVID-19. Lilly's program will test this and other neutralizing antibodies against the virus as both single therapies and combination therapies (i.e., anti- body cocktails). In September 2020, Lilly formed an antibody manufacturing agree- ment with Amgen, through which the companies will have the capabil- ity to quickly scale up production of any of Lilly's antibody therapies that demonstrate clinical effectiveness against SARS-CoV-2 and that receive regulatory approval (13). Amgen, meanwhile, has started it s ow n p r o g r a m t o d e v e l o p Regulatory Sourcebook Pandemic Response FDA has reviewed more than 310 trials, as of the end of August 2020, of potential therapies for treating COVID-19.