We are all longing for the “normal” life after weeks of lockdown due to the COVID-19 pandemic. In Germany the lockdown is gradually eased. But most of us are beginning to understand that normal life might be quite far away as only effective treatment. Finally a commonly available and approved vaccine for Covid-19 can be the key solution.
The long way for vaccines from R&D to approval
Vaccines offer in general the best possible protection against bacterial or viral infections that are often deadly diseases. After vaccination, the serum triggers the creation of antibodies and T cells for virus defense by simulating the infection of the human body by an aggressive pathogen. In this way, vaccination results in the creation of a kind of memory for the immune system. The next time the body is confronted with the specific pathogen, the immune system knows how to react and a disease can be prevented. Some vaccines can even protect for life.
In contrast to treatments, vaccines can effectively flatten the curve of infections in advance. There is only one major problem: A vaccine comes practically always too late for the current wave of infections. As vaccines have to be proven as safe and effective for humans before use, the development, testing and production are very time and resource consuming. Depending on the product, the R&D alone can already take between eight and seventeen years before final approval and a possible market entry. Key factors that influence the process are the existing knowledge about the antigen and its complexity. Such development costs can range from 300 to 800 million euros.
Phases of the approval process of a vaccine
In general, the approval process of a vaccine contains the following phases. In the pre-clinical development, the relevant antigens have to be identified before creating a vaccine concept. It is then evaluated on its efficacy in test tubes and animals. Those vaccine candidates approved by independent authorities can continue the study process towards human clinical testing. The clinical development covers three phases before the final approval and market introduction. In phase 1, small-scale trials with healthy humans test immune response and thus the safety of the serum. In phase 2, a small-scale trial follows with humans from high-risk groups, i.e. those vulnerable regarding the specific virus. Here, effectiveness and dosage are tested. In the final clinical phase 3, a high number of test persons from high-risk groups are vaccinated focussing on adverse reactions of the patients.
Current Covid-19 vaccine projects
Now, the process might be different. Since January 11, 2020, when the genetic sequence of SARS-CoV-2 was published by Chinese researchers, the Coalition for Epidemic Preparedness Innovations (CEPI) is working with global health authorities and vaccine developers to speed up the development of vaccines against the virus. An early available data of the virus combined with the genetic adaptation of already existing technology platforms enabled the rapid creation of vaccine candidates. Yet, the three clinical study phases thereafter are the most time consuming as they have to prove safety and effectiveness.
The World Health Organization (WHO) has published a continually updated list of the confirmed vaccine projects against the novel Coronavirus. Currently, the global COVID-19 vaccine R&D landscape includes more than 100 vaccine candidates. As of 23 April 2020, 77 of the confirmed active projects are at exploratory or preclinical stages with the six most advanced ones already in clinical study phase 1 or 2. Those are originated by US-American, Chinese and British developers. They include the mRNA-1273 from Moderna, Ad5-nCoV from CanSino Biologicals, INO-4800 from Inovio, LV-SMENP-DC, pathogen-specific aAPC from Shenzhen Geno-Immune Medical Institute and ChAdOx1 from the University of Oxford. In Germany, the public Paul-Ehrlich-Institut also approved clinical testing for a range of vaccine candidates of the company BioNTech from Mainz, Germany. Testing will start soon and the first results are expected to arrive in three to five months. They will be decisive for the further study progress.
Covid-19 Vaccine developers mostly in the private industry
The profile of COVID-19 vaccine developers is quite diverse. It ranges from academic research institutes, pharmaceutical multinationals like Sanofi and Pfizer to biotech start-ups. Of the confirmed active vaccine development candidates around 70% are in the private industry. The remaining ones in the academic, public sector, and other non-profit organizations. It is important to note that many of the lead developers are small or inexperienced in large-scale vaccine production. Therefore, the coordination of vaccine manufacturing and supply will be crucial to meet the demand. It is known that developers of active COVID-19 vaccine candidates are located in 19 countries, mainly the US and China. But there is no public information yet about the activities in Africa or Latin America. This development has to be followed closely as a decentralized development of possible vaccines is important to set up resilient supply chains. And this would help to meet the global demand.
Diverse approach in fighting COVID-19
In the sense of clinical vaccine development, there is a broad range of so-called technology platforms. They are currently under evaluation. These platforms include for instance nucleic acid (DNA and RNA), virus-like particles, peptide, viral vector (replicating and non-replicating), recombinant protein, live attenuated virus and inactivated virus approaches. Several of these technologies are not currently the basis for licensed vaccines. But they bring with them encouraging experience from other areas such as oncology. Moreover, the wide range of vaccine candidates is important as some of the platforms may be more or less suited to specific population subgroups, i.e. elderly, children, immunocompromised patients, etc.
Overall, all vaccine candidates have different strengths. The novel vaccine platforms based on DNA or mRNA offer flexibility regarding antigen manipulation. And they also have a high potential for speed and quantity when it comes to manufacturing. Serums made of viral vectors enable a high level of protein expression and are known for long-term stability and high effectiveness, i.e. high immune responses. Others, such as vaccines on recombinant proteins are already licensed for other diseases. They are cases of proven effectiveness against COVID-19. Those vaccine candidates have the big advantage of already existing large-scale production capacity and supply chains.
One interesting example is the vaccine candidate developed by Oxford scientists that have begun human clinical trials on April 23, 2020. Though, vaccine development is normally seen as an uncertain science, this candidate is called ChAdOx1 nCoV-19. It is made from a chimpanzee virus genetically adapted is predicted to have an 80% chance of success.
Development of an effective COVID-19 vaccine
In addition to the vaccine development, the research of an effective treatment for COVID-19 is progressing. This is especially important to fight the current wave of infections. The agent Remdesivir was developed by the US-American company Gilead during the Ebola crisis in 2015. It has shown promise at lowering fever and breathing difficulties. Still, the success of the company is seen as quite controversial due to the company’s reputation to focus mainly on their financial bottom line. Nevertheless, Remdesivir has already been used combined with the Malaria drug Chloroquine in Wuhan since the beginning of 2020. In Germany, the Federal Institute for Drugs and Medical Devices has approved two studies. Those will test the effectiveness of Remdesivir for COVID-19 treatments. Since the beginning of April 2020, the agent is applied to slightly and seriously ill patients in the university hospitals of Hamburg, Munich, and Düsseldorf.
Several vaccine developers have indicated plans to initiate human testing in the rest of 2020. In 2021, risk group patients might be included in the final clinical study phase 3. In some cases, phase 2 and 3 of the clinical phases might be combined to speed up the process. Still, according to experts, it will probably take until 2022 until the vaccine will widely be available.
So, for the current wave of infections, we all are responsible to flatten the curve. We can do this by respecting the public health security measures in place. At the same time, one pillar to fight COVID-19 will be the global supply of protection means. Another will be the development of effective treatment methods available in all regions of the world.
Clevis Research as an expert in the pharmaceutical and eHealth market
Clevis Research has supported several clients in eHealth and the pharmaceutical industry. That is why we are impressed by the current dynamics in the development of a COVID-19 vaccine. We are curious about the major changes the current pandemic will have for those industries. We will follow up on the development closely. For further information, please do not hesitate to ask.
by Meike Winkler
Clevis Research is a market research and advisory boutique. We support clients to pursue global business development opportunities and spark new growth.
David Aberspach, Head of Sales / Team Lead Market & Strategy