Multiple companies are continuously working on developing a potential vaccine that could combat coronavirus. Moderna therapeutics is among the many companies which is working in response to the rapidly growing pandemic of SARS-CoV-2.
Moderna therapeutics’ investigational mRNA vaccine (mRNA-1273) developed against the novel coronavirus is currently being evaluated in clinical trials. In Jan 2020, Moderna’s research team in collaboration with the National Institutes of Health (NIH) finalized the protein sequence which is used in the mRNA vaccine. Moderna started a Phase 1 (NCT04283461) safety and immunogenicity study of mRNA-1273 (2019-nCoV Vaccine) for Prophylaxis of SARS-CoV-2 Infection in March 2020. Positive results from the Phase 1 trial were released on May 18, 2020 which demonstrated an increase in immunogenicity in all the three dose levels.
With mRNA-1273 receiving Fast Track Designation by FDA, this unmet need of the hour is addressed therefore facilitating the development as per the demand
About the mRNA platform- mRNA 1273
mRNA-1273 is a vaccine which encodes for a prefusion stabilized form of the Spike protein. Researchers from the National Institute of Allergy and Infectious diseases (NIAID-part of NIH) in collaboration with Moderna selected the protein. The Coalition for Epidemic Preparedness Innovations (CEPI) funded the first manufactured clinical batch.
The virus was isolated from an infected person in China. The genetic information of the sequenced corona virus was uploaded in a public platform. The sequence of a protein known as the ‘spike protein’, present on the surface of virus was isolated for vaccine development. The isolated spike protein was encoded into a construction molecule called mRNA, which could be used as a vaccine. The vaccine is administered to the patients via injection.
The mRNA instructs immune cells (lymph nodes) to construct multiple copies of the spike protein, creating a situation as if the body has been infected by the virus. Also, other immune cells start developing the spike protein, thereby triggering an immune response which provides protection to the person against the coronavirus.
This approach is different because it does not use a virus for making the vaccine, which is a very rigorous process. Instead, it uses protein sequence information from the virus which is then administered into the patient.
Figure 1- The figure demonstrates the essential steps involved in the mRNA vaccine platform
Further Steps for Moderna’s mRNA-1273 vaccine- Estimated availability of vaccine
- On March 16, 2020, first patient in the Phase 1 study for mRNA-1273 was dosed. The Phase 1 study will test the safety and immunogenicity of mRNA-1273. The study is open-label and expected to enroll 45 adult participants aged between 18 to 55 years.
- On April 27, 2020, An Investigational New Drug application was submitted to the U.S. FDA for Phase 2 and Phase 3 studies of mRNA-1273 if the data from Phase 1 study comes out to be positive.
- Moderna received feedback from the FDA regarding Phase 2 study design, expected to start in Q2-2020. The trial will evaluate the safety, reactogenicity and immunogenicity of two vaccinations of mRNA-1273 given 28 days apart.
- On May 18, 2020, Moderna announced positive interim data of mRNA-1273. The vaccine was also known to be safe and well tolerated
The company is also working on starting a Phase 3 study, provided the data from the Phase 1 and Phase 2 study comes positive. According to Moderna, the Phase 3 study is expected to begin in the early summer of 2020. Moreover, Moderna expects its first potential BLA approval in early 2021.
Although Moderna claims that its earliest versions (under emergency use) for healthcare workers could be available by fall of 2020. Given the conventional way of approval, Moderna expects potential BLA approval in 2021, thereby indicating vaccine availability by early 2021.
Manufacturing/Supply of Vaccine
Moderna therapeutics is working on manufacturing scale-up of mRNA vaccine and has partnered with Lonza for the manufacture and distribution of vaccine doses of mRNA-1273 as soon as possible, provided it proves to be safe and effective.
In May 2020, Moderna announced a 10-year strategic collaboration agreement with Lonza for the large-scale manufacture of Moderna’s mRNA vaccine (mRNA-1273) against the novel coronavirus (SARS-CoV-2) and additional Moderna products in the future.
Moderna is planning to establish manufacturing facilities at Lonza’s facilities in U.S. and Switzerland. Transfer of technologies is expected in June 2020. Moderna and Lonza estimates the manufacturing of mRNA-1273 vaccine (first batches) in July 2020 at Lonza U.S.
The companies also wish to establish additional manufacturing facilities across Lonza’s worldwide manufacturing facilities, allowing for the manufacture of vaccine equivalent to up to 1 billion doses of mRNA-1273 per year for use worldwide assuming the currently expected dose of 50 µg.
Lonza has high experience in mass manufacturing of medicines and has over 50 commercial approvals from regulatory authorities worldwide. This experience will help Moderna in supplying the vaccine at a global level.
Following timeline shows the progress of Moderna therapeutics over the time for mRNA-1273-
BARDA (Biomedical Advanced Research and Development Authority) covers a portion of funding for the establishment of manufacturing facilities at Lonza U.S.
On April 16, 2020, Moderna signed an agreement with BARDA in which the later committed up to $483Mn to Moderna for the accelerated availability of mRNA vaccine into the market.
Under the agreement, BARDA will fund Moderna in all the steps required till FDA approval. BARDA will fund Moderna in its late-stage vaccine development trials and will also provide manufacturing support in its fight against the pandemic. Moderna plans to hire approximately 150 members in the U.S. to support its manufacturing scale-up.
Moderna has estimated that by 2020 they will be able to supply millions of doses per month. By 2021, with increased funding and investments, the supply can reach to tens of millions per month if the vaccine shows effective results and proves successful.
If the experimental vaccine trials are successful, mRNA-1273 vaccine has the potential to become Moderna’s first product as well as the first mRNA vaccine which can combat COVID-19.