Cuban Biopharmaceutical Industry fights COVID-19
The new coronavirus pandemic has challenged the capacity of health systems to respond in most countries. Cuba’s strategy has been recently analyzed in an article published by President Miguel Díaz-Canel and Prof. Jorge Núñez.
One component of this strategy is the Cuban biopharmaceutical industry. The drug coverage of the protocol established by the Ministry of Public Health (MINSAP) was guaranteed. Several products under development were rapidly repositioned for use in covid-19. Biopharmaceuticals such as Nasalferon, Biomodulin-T and Hebertrans have been applied in the prevention of SARS-CoV-2 virus infection in risk groups; Heberon and Heberferon were administered as antiviral treatments, while Jusvinza and Itolizumab were used to stop the hyperinflammatory reaction.
Biotechnology products have contributed to the decrease of severe and critical patients ( <7 %) and to the reduction of mortality (0.8/100 000) from this disease, approximately 10 times less than the global rate.
The project portfolio includes other antiviral and immunomodulatory biological products, diagnostic reagent kits, natural products and medical equipment, and several vaccine candidates are under development, which should contribute to the definitive control of this disease in Cuba.
The biopharmaceutical industry in Cuba The Cuban biopharmaceutical industry was created over 35 years ago by Commander in Chief Fidel Castro, who also drove its growth and development.
Since the beginning of modern biotechnology, based on genetic engineering techniques, Cuba has been inserted in this emerging sector and has established its own model of science and innovation that has obtained results recognized by the international community.
The National Center for Scientific Research (CNIC), founded in 1965, would become a source of scientists who would be responsible for creating other institutions, most of them related to animal and human health.
The 1980s saw the take-off of biotechnology, with the creation of the Biological Front and the inauguration of the Biological Research Center in 1982, the Center for Genetic Engineering and Biotechnology (CIGB) in 1986, the Immunoassay Center (CIE) in 1987, and other institutions that in 1992 formed the Havana Science Center, which has more than 10,000 workers.
In 2012, these institutions merged with the pharmaceutical industry companies, giving rise to the superior business organization BioCubaFarma, which today groups 32 companies, supplies more than 800 products to the health system – including 349 medicines in the Basic Table –, has 182 patent objects, carries out more than 100 simultaneous clinical trials with its products in 200 clinical sites, and has exported its products to more than 50 countries.
Cuban experiences in the fight against epidemics The Cuban biopharmaceutical sector has participated, as part of the health system, in confronting complex epidemiological situations on a national scale, and has accumulated vast experience working in this area. Some examples are: dengue, bacterial meningitis and AIDS control, with satisfactory results.
BioCubaFarma and COVID-19: The contribution of science and innovation The development and consolidation of a mature biopharmaceutical industry, with scientific and innovative capacity, is expressed in a wide portfolio of products and projects of BioCubaFarma, which has been a strength for the Cuban health system in the management of this disease.
The Ministry of Public Health and BioCubaFarma developed a joint research programme for the prevention and treatment of the disease, which began in February 2020, before the first case was reported in the country. This research program, which started with a few projects, reached until June dozens of basic researches, clinical and medical interventions, for the prevention of the disease in risk and vulnerable groups, the treatment of confirmed patients, the treatment of serious and critical patients, as well as the recovery of convalescents.
Main results BioCubaFarma has worked on 16 projects of new treatments and medical technologies to prevent and fight covid-19, caused by the coronavirus SARS-Cov-2. Of these, there are 11 products that are in clinical studies or intervention trials in patients and risk groups. For preventive purposes, five products capable of stimulating both innate and adaptive immunity for different risk groups (including medical personnel) have been evaluated.
Because of their antiviral action, four products have been used on newly diagnosed patients infected with the virus, and two to counteract the cytokine storm process. Work is being done on three diagnostic systems at the ICN and the national production of artificial respirators, coordinated by the Cuban Neuroscience Centre.
BioCubaFarma’s products and scientific projects are inserted in all disease control areas.
Biomodulin-T, a natural origin immunomodulator Biomodulin-T is a bovine thymus extract containing low molecular weight polypeptides (less than 20 kDa), produced by the Biopreparations Center of Cuba (Biocen), in collaboration with the Institute of Hematology and Immunology, MINSAP.
It is an effective immunomodulator in the treatment of respiratory diseases in older adults that stimulates the production of CD4 and CD8 T-lymphocytes and the differentiation of thymus lymphoblastoid cells.
Hebertrans (Transfer Factor) Transfer Factor is a blood product obtained by leukocyte hemodialysis, which transfers immunity from an immune donor to an immune-deficient recipient.
Nasalferon (nasal formulation of recombinant human IFN alpha-2b) Nasalferon is a recombinant human IFN-alpha-2b formulation for nasal administration that, thanks to the immunomodulatory and antiviral properties of IFNalpha, achieves protection against exposure to SARSCoV- 2.
Heberon® (recombinant human interferon alpha-2b) Several clinical studies have provided evidence of the antiviral effects of type I interferons in patients with respiratory coronaviruses. In patients infected with SARSCoV- 2 during the first month after the outbreak in Cuba, the therapeutic efficacy of IFN alfa-2b was evaluated in a metacentric prospective observational study conducted in 16 hospitals in eight Cuban provinces.
Heberferon® (IFN alpha-2b + IFN gamma) In 2016 the Center for Genetic Engineering and Biotechnology (CIGB) obtained the registration of a new formulation, Heberferon®, which combines alpha-2b and gamma interferons, and whose use was approved for the treatment of basal cell carcinoma, the most common skin cancer.
Jusvinza, immunomodulating peptide Patients with covid-19 who are moving towards severe and critical stages present a marked hyperinflammation. This stage of the disease is mediated by high concentrations of pro-inflammatory cytokines, a biological event known as “cytokine storm”.
This drug is an immunomodulatory peptide, designed by bioinformatic tools, which has anti-inflammatory properties.
Itolizumab, anti-CD6 monoclonal antibody The CD6 glycoprotein is considered a leukocyte differentiation antigen. It is expressed primarily in mature peripheral blood T cells, where it constitutes the majority of the CD3+ cell population. It is also expressed in a much smaller proportion in a fraction of mature B cells (B1a cells), in immature thymocytes and in neurons of the cerebral cortex. The use of Itolizumab in psoriasis and rheumatoid arthritis showed its safety and efficacy.
Other drugs under evaluation Some products in development are: - CIGB300 peptide, casein kinase enzyme inhibitor. - VAMENGO-BC antimeningococcal vaccine, and CIGB2020 vaccine (based on hepatitis B virus antigens), both used in clinical studies as an alternative. - Specific SARS-CoV-2 vaccines. Projects related to diagnosis are also underway: - Serological diagnosis based on SUMA technology, from the Immunoassay Centre. - Molecular diagnosis.
The coronavirus pandemic has been an enormous challenge for the whole of Cuban society. The response has been multiple and successful. Now it is necessary to analyze it and draw the lessons that will be useful for the new challenges to come, since the health situation in the world is heading towards an uncertain and dangerous future.
The positive results in the fight against the epidemic in Cuba are directly related to Cuba’s cohesion and capacity for social mobilization, the Government’s leadership of the process, the strengths of the health system, built up over more than 60 years, and also the institutionality and response of the scientific community, with the integrated participation of the pharmaceutical and biotechnology industry.
Article summary published by the magazine Anales de la Academia de Ciencias de Cuba.
Martínez-Díaz E, Pérez-Rodríguez R, Herrera-Martínez L, Lage-Dávila A, Castellanos-Serra L. La industria biofarmacéutica cubana en el combate contra la pandemia de COVID-19. Anales de la Academia de Ciencias de Cuba [revista en Internet]. 2020 [citado 2020 Ago 20]; 10(2):[aprox. 0 p.]. Disponible en: http://www.revistaccuba.cu/index.php/revacc/article/view/906
- Eduardo Martínez Díaz , President of BioCubaFarma. Full Academician, Cuban Academy of Sciences. Havana. Cuba.
- Rolando Pérez Rodríguez , Science and Innovation Director of BioCubaFarma. Academic of Merit, Cuban Academy of Sciences. Havana. Cuba.
- Luis Herrera Martínez , Advisor to the President of BioCubaFarma. Academic of Merit, Cuban Academy of Sciences. Havana. Cuba.
- Agustín Lage Dávila , Advisor to the President of BioCubaFarma. Academic of Merit, Cuban Academy of Sciences. Havana. Cuba.
- Lila Castellanos Serra , Academician of Merit, Cuban Academy of Sciences Havana. Cuba.