Pipeline Progress
“Their success is a scientific feat with few parallels. No vaccine has ever been developed so quickly before, never mind readied for widespread use and manufactured at scale.”
That was the verdict of By Jonathan Gardner, Ned Pagliarulo and Ben Fidler in a recent report on coronavirus vaccines in BioPharma Dive.
As of June 1, Moderna has joined Pfizer and BioNTech in asking for full FDA approval of its shot. Scientists, pharmaceutical companies and government officials have moved at incredible speed to develop and bring to market multiple vaccines for the new coronavirus. Several companies have proven that their vaccines can strongly protect against COVID-19. Nearly a dozen shots from developers in the U.S., U.K., Germany, China and Russia have now been cleared by regulators around the world.
Developers include Moderna, CanSino Biologics, Inovio, Sinovac, BioNTech/Pfizer, University of Oxford/AstraZeneca, Sinopharm/Beijing Institute, Novavax, Gamaleya Research Institute, CureVac, Clover Biopharmaceuticals, Johnson & Johnson, Sanofi/GlaxoSmithKline and Merck & Co.
While efficacy estimates indicate protection from symptomatic COVID-19, there are some differences between clinical trial measurements. Not all estimates are directly comparable, and vaccines may not protect against new variants. Estimates for Pfizer, Moderna, Gamaleya, Novavax, J&J, Sinovac and AstraZeneca come from a single trial, but AstraZeneca also has data available from other, smaller studies. Governments invested huge amounts of money into vaccine research and development and to prepare to make and distribute the billions of doses necessary to curb the pandemic.
Immunization campaigns in process could determine whether the virus recurs year after year or is ultimately stopped. Doses of authorized vaccines remain in short supply worldwide, however, and access has involved lucrative deals struck between drugmakers and wealthy countries.
What enabled some companies to cross the finish line faster was messenger RNA technology. This drug-making approach uses genetic instructions to teach cells to make proteins. It can be used to build a vaccine more easily than traditional methods. In the case of Moderna’s coronavirus vaccine, the evolution went from a computer design in January 2020 to human study in just three months, making it the first U.S. company to reach that point. Phase 1 results came in late May, as well as the beginning of a mid-stage trial. A Phase 3 study started on July 27. Four months later, there were strongly positive results that showed that the vaccine was 94 percent effective in preventing COVID-19.
While initial supplies were limited to several tens of millions of doses, Moderna and its partners ramped up production quickly. The U.S. contracted to buy another 100 million doses from Moderna on February, bringing its total on order to 300 million. Moderna and contract manufacturer Catalent agreed to expand their work together, dedicating a high-speed production line through June 2023. There are questions about how long the protection from the first generation of mRNA vaccines will last, and whether they will be equally protective against virus variants first identified in South Africa and Brazil. There may be a need for booster shots. Moderna is testing a booster designed to counter the South African variant and a shot combining both of them. Early results from an ongoing study showed the first two concepts appear to work as intended, raising antibody levels against the variants, but not as high as they were against the original virus. On June 1, Moderna began the process of formally asking the FDA for full approval of its shot, an important step that will allow the vaccine to remain available once the COVID-19 emergency ends.
While Moderna was pushing forward with messenger RNA technology, BioNTech of Germany started work on an mRNA vaccine for the coronavirus and agreed to partner with Pfizer in March 2020, even before their legal teams had produced a contract. The partnership won clearance from the U.K. drugs regulator for their shot just eight months later, followed quickly by authorization in Canada on December 9 and an emergency clearance from the FDA on December 11. Authorities in the EU granted conditional authorization on December 21.
Pfizer and BioNTech had advanced four prototypes, each with subtle differences, before choosing one to take into late-stage testing. A Phase 2/3 trial that started on July 28 enrolled 44,000 volunteers in three months. Trial data showed a better-than-expected 95 percent efficacy in preventing COVID-19 with minimal side effects (injection site pain, fatigue and fever). In March, use of the vaccine in Israel confirmed the efficacy (97 percent against symptomatic COVID-19). Results also showed protection against asymptomatic infection. The shot was completely effective in a study of 12- to 15-year-olds. On May 10, the FDA authorized the vaccine’s use in that age group.
In May Pfizer became the first developer to seek a full U.S. approval of a coronavirus shot. A positive FDA decision would clear post-pandemic use. Pfizer is projecting $26 billion in sales for the vaccine’s first year on the market, a record number for a pharmaceutical product. The spread of virus variants raised questions about whether Pfizer and BioNTech vaccine will remain as strongly effective. Positive results released from a study in Qatar indicated that the shot was still 75 percent effective against the South African variant and provided near-complete protection against severe disease. Pfizer and BioNTech are looking at a second booster shot and a variant-specific vaccine.
Pfizer and BioNTech have contracted to supply the U.S. with 300 million doses, the most recent order coming February 12. They have agreed to supply the EU with up to 1.8 billion doses through 2023. Lucrative supply deals like those with the U.S. and Europe have resulted in huge sales for both companies. Pfizer expects $26 billion in revenue from the shot this year, a historically large sum equivalent to more than half its overall sales in 2020. Pfizer and BioNTech have had help from Sanofi, Novartis and Merck KGaA in producing and filling vials of their vaccine.
Johnson&Johnson was the first among larger drugmakers to pursue a coronavirus vaccine, announcing its plans in January 2020 plans to develop one using the same technology that underpins several other of its experimental vaccines. Initially, J&J was going to begin a clinical study in September 2020, but the company sped up its plans, securing help from the U.S. government through Operation Warp Speed. An initial study began in late July. On September 23, J&J began a global Phase 3 study.
J&J was going to recruit 60,000 volunteers but reduced its enrollment target after cases of COVID-19 began to accelerate rapidly in the U.S. during the late fall. On December 17, the drugmaker announced the study had been fully enrolled with approximately 45,000 participants. In January 2021, data from the study showed that a single dose of J&J’s vaccine was 66 percent effective in preventing moderate or severe COVID-19. Efficacy was higher among participants recruited in the U.S., but lower in volunteers in Latin American and South Africa, where more virulent variants of SARS-CoV-2 are prevalent.
Nonetheless, the J&J shot can be given via one injection and shipped at normal refrigerator temperatures. On February 27, the U.S. FDA granted it emergency authorization, making it the third vaccine available in the country. European regulators followed with a conditional authorization on March 11. Reports of blood clots near the brain combined with low platelet counts caused the FDA and CDC to recommend pausing use of J&J’s shot on April 13, causing J&J to delay the vaccine’s rollout in Europe. There were few cases of blood clots, but they concerned regulators because the symptoms were similar to a side effect linked to AstraZeneca’s vaccine, which uses a similar technology. On April 23 a CDC panel decided that the benefit of protecting against COVID-19 outweighed the risk of the rare side effect. The FDA cleared vaccinations to continue.
J&J plans to supply 1 billion doses of its vaccine, with 200 million set to go to the U.S. The company delivered 20 million doses to the U.S. by the end of March and expects to deliver the rest by the end of June. Europe bought 200 million doses, an order Catalent is helping to fill by reserving two production lines at a plant in Italy. The Biden administration helped to broker a deal involving Merck & Co., which agreed to help J&J make its vaccine and fill vials for shipping. Officials expect the collaboration could expand the number of doses produced, but production hit a setback in March and April. As of June 1, the factory was still not authorized to ship out the vaccine because of an investigation into contamination.
Many other companies around the world are working on vaccines. Some are in use in other countries. In any case, the speed of getting the vaccines developed, manufactured and distributed has been nothing short of remarkable.
