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Moderna COVID-19 vaccine

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Moderna COVID-19 vaccine
Vaccine description
TargetCOVID-19
Vaccine typemRNA
Clinical data
Routes of
administration		Intramuscular injection
Legal status
Legal status

mRNA-1273 is a COVID-19 vaccine candidate developed by NIAID, BARDA and Moderna given by intramuscular injection.

Design and Phase I-II trials

In January 2020, Moderna announced development of an RNA vaccine, named mRNA-1273, to induce immunity to SARS-CoV-2.[1][2][3] Moderna's technology is a nucleoside-modified messenger RNA (modRNA) compound named mRNA-1273, which induces immunity to SARS-CoV-2 by encoding a prefusion stabilized spike (S) protein naturally present on the surface of SARS-CoV-2 particles. From the announcement, Moderna's shares rose dramatically, and the CEO and other corporate executives began large program sales of their shareholdings.[4]

In March 2020, the Phase I human trial of mRNA-1273 began in partnership with the US National Institute of Allergy and Infectious Diseases.[5] In April, the U.S. Biomedical Advanced Research and Development Authority (BARDA) allocated up to $483 million for Moderna's vaccine development.[6] Plans for a Phase II dosing and efficacy trial to begin in May were approved by the FDA.[7] Moderna signed a partnership with Swiss vaccine manufacturer Lonza Group,[8] to supply 300 million doses per annum.[9]

On May 25 2020, Moderna began a Phase IIa clinical trial recruiting 600 adult participants to assess safety and differences in antibody response to two doses of its candidate vaccine, mRNA-1273, a study expected to complete in 2021.[10] In June 2020, Moderna entered a partnership with Catalent in which Catalent will fill and package the vaccine candidate. Catalent will also provide storage and distribution.[11]

On July 9, Moderna announced an in-fill manufacturing deal with Laboratorios Farmacéuticos Rovi, in the event that its vaccine is approved.[12]

On 14 July 2020, Moderna scientists published preliminary results of the Phase I dose escalation clinical trial of mRNA-1273, showing dose-dependent induction of neutralizing antibodies against S1/S2 as early as 15 days post-injection. Mild to moderate adverse reactions, such as fever, fatigue, headache, muscle ache, and pain at the injection site were observed in all dose groups, but were common with increased dosage. [13][14] The vaccine in low doses was deemed safe and effective in order to advance a Phase III clinical trial using two 100-μg doses administered 29 days apart.[13]

In July 2020, Moderna announced in a preliminary report that its Operation Warp Speed candidate had led to production of neutralizing antibodies in healthy adults in Phase I clinical testing.[13][15] "At the 100-microgram dose, the one Moderna is advancing into larger trials, all 15 patients experienced side effects, including fatigue, chills, headache, muscle pain, and pain at the site of injection."[16] The troublesome higher doses were discarded in July from future studies.[16]

Criticisms

In May 2020, after releasing partial and non-peer reviewed results for only 8 of 45 candidates in a preliminary pre-Phase I stage human trial direct to stock markets, the CEO announced on CNBC an immediate $1.25 billion rights issue to raise funds for the company, at a $30 billion valuation.[17] while Stat said, "Vaccine experts say Moderna didn't produce data critical to assessing COVID-19 vaccine".[18]

On July 7, disputes between Moderna and government scientists over the company's unwillingness to share data from the clinical trials were revealed.[19]

Phase III trials

Moderna and the National Institute of Allergy and Infectious Diseases began a Phase III trial in the United States on 27 July with a plan to enroll and assign 30,000 volunteers to two groups — one group receiving two 100-μg doses of mRNA-1273 vaccine and the other receiving a placebo of 0.9% sodium chloride.[20] As of 7 August, over 4,500 volunteers had enrolled.

In September 2020, Moderna published the detailed study plan for the clinical trial.[21] On 30 September, CEO Stéphane Bancel said that, if the trial is successful, the vaccine might be available to the public as early as late March or early April 2021.[22] As of October 2020, Moderna had completed the enrollment of 30,000 participants needed for its Phase III trial.[23]

On 16 November 2020, Moderna announced preliminary data from its Phase III clinical trial, indicating 94% efficacy in preventing COVID-19 infection.[24][25] Side effects included flu-like symptoms, such as pain at the injection site, fatigue, muscle pain, and headache.[24] The Moderna results were not final – as the trial is not scheduled to conclude until late-2022[26] – and were not peer-reviewed or published in a medical journal.[24] The US National Institutes of Health announced on 15 November 2020 that overall trial results were positive.[27]

It remains unknown whether the Moderna vaccine candidate is safe or effective in people under age 18, how long it provides immunity, whether it requires a booster shot,[24] or whether it is effective in people of color.[28] The Moderna news followed preliminary results from the Pfizer-BioNTech vaccine candidate, BNT162b2, with Moderna demonstrating similar efficacy, but requiring storage at the temperature of a standard medical refrigerator of 2–8 °C (36–46 °F) for up to 30 days or −20 °C (−4 °F) for up to 4 months, whereas the Pfizer candidate requires ultracold freezer storage at −70 °C (−94 °F).[24]

In November 2020, Nature reported that "While it's possible that differences in LNP formulations or mRNA secondary structures could account for the thermostability differences [between Moderna and BioNtech], many experts suspect both vaccine products will ultimately prove to have similar storage requirements and shelf lives under various temperature conditions".[29]

Since September 2020, Moderna has used Roche Diagnostics' Elecsys® Anti-SARS-CoV-2 S test, approved by the US FDA on November 25, 2020. According to an independent supplier of clinical assays in microbiology, "this will facilitate the quantitative measurement of SARS-CoV-2 antibodies and help to establish a correlation between vaccine-induced protection and levels of anti-receptor binding domain (RBD) antibodies". The partnership was announced by Roche on December 9, 2020.[30]

Purchase commitments

On 11 August 2020, the US government signed an agreement to buy 100 million doses of Moderna's anticipated vaccine,[31] which the Financial Times said Moderna planned to price its vaccine between $50–60 per course.[32] On November 2020, Moderna has stated that it will charge governments who purchase its vaccine between $25 and $37 per dose while the EU is seeking a price of under $25 per dose for the 160 million doses it plans to purchase from Moderna.[33][34]

In late 2020, Moderna also obtained purchase agreements for mRNA-1273 with the European Union for 160 million doses and with Canada for up to 56 million doses.[35][36]

Emergency use authorization

During October-December 2020, mRNA-1273 was under evaluation for emergency use authorization (EUA) which would enable rapid rollout of the vaccine in the United Kingdom, the European Union, Canada, and the United States.</ref>[37][38][39][40]

On 18 December 2020, mRNA-1273 was approved by the United States FDA under an emergency use authorization.[41] This is the first product from Moderna that has been approved by the FDA.[42]

Patent litigation

The PEGylated lipid nanoparticle (LNP) drug delivery system of mRNA-1273 has been the subject of ongoing patent litigation with Arbutus Biopharma, from whom Moderna had previously licensed LNP technology.[43][44] On September 2020, Nature Biotechnology reported that Moderna had lost a key challenge in the ongoing case.[45]

See also

References

  1. ^ Steenhuysen, Julie; Kelland, Kate (24 January 2020). "With Wuhan virus genetic code in hand, scientists begin work on a vaccine". Reuters. Archived from the original on 25 January 2020. Retrieved 26 January 2020.
  2. ^ Karen Carey (26 February 2020). "Increasing number of biopharma drugs target COVID-19 as virus spreads". BioWorld. Archived from the original on 27 February 2020. Retrieved 1 March 2020.
  3. ^ Gwen Everett (27 February 2020). "These 5 drug developers have jumped this week on hopes they can provide a coronavirus treatment". Markets Insider. Archived from the original on 16 November 2020. Retrieved 1 March 2020.
  4. ^ Pendleton, Devon; Maloney, Tom (18 May 2020). "MIT Professor's Moderna Stake on the Brink of Topping $1 Billion". Bloomberg News. Retrieved 18 May 2020. CEO Bancel, other Moderna executives have been selling shares
  5. ^ "NIH clinical trial of investigational vaccine for COVID-19 begins". National Institutes of Health (NIH). 16 March 2020. Archived from the original on 19 March 2020. Retrieved 18 March 2020.
  6. ^ Kuznia, Robert; Polglase, Katie; Mezzofiore, Gianluca (1 May 2020). "In quest for vaccine, US makes 'big bet' on company with unproven technology". CNN. Archived from the original on 13 May 2020. Retrieved 2 May 2020.
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  8. ^ Kyle Blankenship (1 May 2020). "Moderna aims for a billion COVID-19 shots a year with Lonza manufacturing tie-up". FiercePharma. Archived from the original on 16 November 2020. Retrieved 9 May 2020.
  9. ^ "Swiss factory rushes to prepare for Moderna Covid-19 vaccine". SWI swissinfo.ch. Archived from the original on 16 November 2020. Retrieved 7 October 2020.
  10. ^ Clinical trial number NCT04405076 for "Dose-Confirmation Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of mRNA-1273 COVID-19 Vaccine in Adults Aged 18 Years and Older" at ClinicalTrials.gov
  11. ^ Staff, Reuters (25 June 2020). "Moderna eyes third quarter for first doses of potential COVID-19 vaccine with Catalent deal". Reuters. Archived from the original on 16 November 2020. Retrieved 6 November 2020. {{cite news}}: |first= has generic name (help)
  12. ^ Lee, Jaimy. "Moderna signs on for another COVID-19 vaccine manufacturing deal". MarketWatch. Archived from the original on 16 November 2020. Retrieved 9 July 2020.
  13. ^ a b c Lisa A Jackson; mRNA-1273 Study Group (July 2020). "An mRNA Vaccine against SARS-CoV-2 — Preliminary Report". The New England Journal of Medicine. 383 (20): 1920–1931. doi:10.1056/NEJMoa2022483. PMC 7377258. PMID 32663912.{{cite journal}}: CS1 maint: numeric names: authors list (link)
  14. ^ Lisa A Jackson; mRNA-1273 Study Group (July 2020). "Supplementary appendix for 'An mRNA Vaccine against SARS-CoV-2 — Preliminary Report'" (PDF). The New England Journal of Medicine. doi:10.1056/NEJMoa2022483. PMC 7377258. PMID 32663912. Archived (PDF) from the original on 14 July 2020. Retrieved 15 July 2020.{{cite journal}}: CS1 maint: numeric names: authors list (link)
  15. ^ Yun Li (14 July 2020). "Dow futures jump more than 200 points after Moderna says its vaccine produces antibodies to coronavirus". CNBC. Archived from the original on 16 November 2020. Retrieved 15 July 2020.
  16. ^ a b Herper, Matthew; Garde, Damian (14 July 2020). "First data for Moderna Covid-19 vaccine show it spurs an immune response". Boston Globe Media. statnews.com. Archived from the original on 14 July 2020. Retrieved 15 July 2020.
  17. ^ Hiltzik, Michael (19 May 2020). "Column: Moderna's vaccine results boosted its share offering – and it's hardly a coincidence". The Los Angeles Times. Archived from the original on 16 November 2020. Retrieved 19 May 2020.
  18. ^ Branswell, Helen (19 May 2020). "Vaccine experts say Moderna didn't produce data critical to assessing Covid-19 vaccine". Stat. Archived from the original on 16 November 2020. Retrieved 19 May 2020.
  19. ^ Taylor, Marisa; Respaut, Robin (7 July 2020). "Exclusive: Moderna spars with U.S. scientists over COVID-19 vaccine trials". Reuters. Archived from the original on 16 November 2020. Retrieved 10 July 2020.
  20. ^ Palca, Joe (27 July 2020). "COVID-19 vaccine candidate heads to widespread testing in U.S." NPR. Archived from the original on 11 October 2020. Retrieved 27 July 2020.
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  22. ^ Mascarenhas, Lauren (1 October 2020). "Moderna chief says Covid-19 vaccine could be widely available by late March". CNN. Archived from the original on 16 November 2020. Retrieved 2 October 2020.
  23. ^ Correspondent, Elizabeth Cohen, CNN Senior Medical. "First large-scale US Covid-19 vaccine trial reaches target of 30,000 participants". CNN. Archived from the original on 16 November 2020. Retrieved 23 October 2020. {{cite web}}: |last= has generic name (help)CS1 maint: multiple names: authors list (link)
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  25. ^ Zimmer, Carl (20 November 2020). "2 Companies Say Their Vaccines Are 95% Effective. What Does That Mean? You might assume that 95 out of every 100 people vaccinated will be protected from Covid-19. But that's not how the math works". The New York Times. Retrieved 21 November 2020.
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  30. ^ "Moderna Use Roche Antibody Test During Vaccine Trials". rapidmicrobiology.com. Retrieved 13 December, 2020.
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  32. ^ "Moderna pitches virus vaccine at about $32-$37 per course". Financial Times. 5 August 2020. Archived from the original on 16 November 2020. Retrieved 29 July 2020.(subscription required)
  33. ^ "Donald Trump appears to admit Covid is 'running wild' in the US". The Guardian. 22 November 2020. ISSN 0261-3077. Retrieved 22 November 2020. Moderna told the Germany [sic] weekly Welt am Sonntag that it will charge governments between $25 and $37 per dose of its Covid vaccine candidate, depending on the amount ordered.
  34. ^ Guarascio, Francesco (24 November 2020). "EU secures 160 million doses of Moderna's COVID-19 vaccine". Reuters. Retrieved 25 November 2020.
  35. ^ "Coronavirus: Commission approves contract with Moderna to ensure access to a potential vaccine". European Commission. 25 November 2020. Retrieved 4 December 2020.
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  41. ^ Jr, Berkeley Lovelace (19 December 2020). "FDA approves second Covid vaccine for emergency use as it clears Moderna's for U.S. distribution". CNBC. Retrieved 19 December 2020.
  42. ^ Lee, Jaimy. "Moderna nears its first-ever FDA authorization, for its COVID-19 vaccine". MarketWatch. Retrieved 19 December 2020.
  43. ^ Auth, Dorothy R.; Powell, Michael B. (14 September 2020). "Patent Issues Highlight Risks of Moderna's COVID-19 Vaccine". New York Law Journal. Retrieved 1 December 2020.
  44. ^ Vardi, Nathan (29 June 2020). "Moderna's Mysterious Coronavirus Vaccine Delivery System". Forbes. Retrieved 1 December 2020.
  45. ^ "Moderna loses key patent challenge". Nature Biotechnology. 38 (1009): 1009. 2020. doi:10.1038/s41587-020-0674-1. PMID 32887970. S2CID 221504018. Retrieved 1 December 2020.
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