BioCubaFarma in the COVID-19 battle

Photo: Ricardo López Hevia

To learn about progress being made in scientific research to identify new products to treat COVID-19, Granma interviews Dr. Eduardo Martínez Díaz, president of the BioCubaFarma Enterprise Group:

-What has the Cuban biotechnology and pharmaceutical industry been doing to confront COVID-19?

-Our Enterprise Group has a specific plan with four fundamental components which are

*Supply medicines included in the COVID-19treatment protocol established by the Ministry of Public Health (Minsap).

*Research and development to provide new products and knowledge to combat this virus

*Cooperation with other countries in supplying drugs to fight the pandemic

*Take steps internally within our companies to protect workers and guarantee operations under current circumstances

-How many products does BioCubaFarma currently provide for Cuba’s COVID-19 treatment protocol?

-At the beginning, 22 medicines were identified, several anti-virals, primarily Interferon, and an important group of drugs for hospital use with patients in different phases, including those in serious and critical condition. We currently have stocks of these for thousands of patients and continue to expand production capacity.

BioCubaFarma companies have added production of face masks and sanitizing products such as medicinal soaps, hypochlorite solution, hydroalcoholic solutions, etc.

Likewise, based on the capacity of our equipment and device plants, in collaboration with other companies in the country and self-employed workers, we are working on the repair of equipment much-needed to confront the pandemic, including ventilators, while we are also manufacturing individual protective wear, mainly masks with filters, visors, goggles and suits.”

-What are the most significant scientific advances?

-We initially created a BioCubaFarma working group and activated our Scientific Council commissions, to focus on confronting the epidemic. One of the ongoing tasks has been the search for information, the study of the characteristics of the virus and the behavior of the pandemic in general.

Information processing has allowed us, in a relatively short period of time, to make proposals for the use of drugs and their incorporation into the treatment protocol, or for their initial clinical evaluation.

Today we know that once infection with sars-CoV-2 has occurred, a patient’s condition can take two different paths: Eighty percent of those infected experience a mild case of the disease or are asymptomatic; 20% develop complications and serious or critical conditions. Unfortunately, the average fatality rate globally is above 5% and in some countries exceeds 10%.

The difference between first group and the second is mainly in the status of the infected person’s immune system. Severe cases are known to show 60 times the viral load of mild cases. This occurs because people with weak immune systems do not respond immediately to infection and this virus, which has a high capacity for reproduction, rapidly reaching high levels of copies.

Several risk groups, which all tend to have weak immune systems, have been identified and are more vulnerable to complications when infected with the new coronavirus.

These risk groups include adults over 60 years old, persons with immunosuppressive diseases, diabetes, cancer, high blood pressure, etc.

In view of this scenario, we are focused on developing medications to strengthen the immune systems of vulnerable patients, drugs with antiviral effect and those to prevent deaths among serious and critical patients.

During the last few weeks, Biomodulin t and Transfer Factor, two drugs that strengthen the immune system, have been included in the COVID-19 protocol. A variant of interferon is also being produced for nasal administration, which will be used as a preventive.

On the other hand, two broad-spectrum vaccines are being evaluated to stimulate the innate immune system. They are new types of vaccines that we have been working on, precisely to ”train” the immune systems of those who are susceptible to viral infections.

Such products allow the body to be prepared to develop a more effective immune response once infected. These vaccines could soon be incorporated into the protocol for combating COVID-19.

-What is being done to prevent the deaths of critically or seriously ill patients?

-As I mentioned earlier, patients in serious condition may develop a viral load 60 times higher than those with a mild case of the disease. This high viral load produces a response in the organism, which leads to what is called a “cytokine storm,” causing a process of hyperinflation that aggravates the patient’s condition.

Based on this information, we have studied in detail the molecular mechanisms and have identified drugs with the capacity to stop this ”cytokine storm”, which can cause the death of patients in a short period of time.

Similarly, we proposed two medications to the Minsap expert group for use with serious and critical patients. After a rigorous analysis, their evaluation was approved in a controlled manner. It should be noted that these drugs have been certified pharmacologically as safety and effective in treating other diseases under study.

Thus far, these drugs have been used in several patients with COVID-19 and we are beginning to see encouraging results, although of course we need to wait for more evidence to determine that the products are having the desired effect and saving lives.

-I have read news reports stating that interferon has not been clinically proven as effective against COVID-19?

-None of the products used worldwide today in the treatment of COVID-19 have any clinical evidence demonstrated in a controlled study. There has not been enough time to conduct clinical trials with all the necessary rigor to evaluate the efficacy of any specific drug in this pandemic.

A large number of drugs have been proposed and approved by regulatory authorities in countries around the world. We are doing the same. For example, each proposal from our scientists is analyzed by the BioCubaFarma working group and then presented to a group of experts at Minsap – including several from Cecmed and the Coordinating Center for Clinical Studies (Cencec) – where they may approved.

We have established special mechanisms for the rapid evaluation and approval of the protocols, while always maintaining a high level of rigor.

In the case of Recombinant Human Interferon Alpha 2b, produced in our country, it is included in the COVID-19 treatment protocol, along with other chemical antivirals. Interferon helps the body fight the virus by activating the immune system and mechanisms that inhibit viral replication.

We know that since the beginning of the epidemic in China, Interferon was incorporated into the treatment protocol. Based on results obtained, this drug was recommended by expert consensus and became part of the therapeutic guidelines that were approved, not only in China, but also in other countries.

In the particular case of Cuba, the use of this drug in the COVID-19 epidemic has shown very positive results in terms of preventing patients from evolving toward serious condition.

-Are you working on specific preventive vaccines for this virus?

-The number of person infected who remain asymptomatic has not been documented in the specialized literature yet. These patients are one of the fundamental causes of the epidemic’s rapid expansion, hence the importance of active research to identify and isolate these individuals.

Today, what is needed in continuing to live this epidemic, containing transmissions in order to manage the situation until a specific preventive vaccine is developed. Reports indicate that work is underway on 60 vaccine candidates worldwide and human trials have begun for two.

We are focused on developing specific preventive vaccines for this virus, as well. We have designed four candidates and are working quickly to begin testing them in animal models as soon as possible.

-Are you working on the development of diagnostic systems?

-Yes, the pcr test, as it is known, (Polymerase Chain Reaction) in real time is the key to confirming cases of the virus. Rapid diagnostic systems have been developed to measure antibodies, which are produced when an infection occurs.

We are working on the development of an Elisa (Enzyme-Linked ImmunoSorbent Assay) system based on our Ultramicro-Analytic System (SUMA) technology, which should be available in the coming weeks. It is really a challenge to have the system set up and tested in such a short time, but we are working hard to achieve this.