COVID-19 vaccines and the pandemic's third year

Pfizer and BioNTech on Nov. 4 released updated clinical trial results for their omicron-adapted booster shot for COVID-19. The new data, which detail immune responses after one month, follow earlier data evaluating the vaccine after seven days.

According to Pfizer and BioNTech, booster vaccination in adults between 18 and 55 years old raised antibody levels against the BA.4 and BA.5 omicron variants by nearly 10-fold compared to pre-booster levels. The additional shot raised antibody levels more than 13-fold in adults over 55 years old, the companies said.

Uptake of the boosters remain slow and the companies don’t yet have evidence showing relative effectiveness between their new shot and the old one on outcomes like infection and disease. New omicron substrains, meanwhile, are gaining prevalence, a development that Pfizer and BioNTech said they were monitoring.

Pfizer and BioNTech’s updated booster was quickly made ready in time for a campaign by the Biden administration to encourage vaccination before the flu and winter season. The Food and Drug Administration’s authorization came based on limited preclinical data, as well as trial results from a similar, but different reformulation of the companies’ original shot.

Pfizer and BioNTech initially shared seven-day immune response data in mid-October, but they did not reveal specific data.

The latest results provide more details supporting the added protection offered by the new booster. In adults over the age of 55, the bivalent booster increased omicron antibodies by substantially more than Pfizer and BioNTech’s original vaccine, which drove a 2.9-fold increase in antibody levels.

However, more data are still needed, such as to compare the relative increase in antibodies in younger adults, as well as in children. Other smaller studies have found little comparative advantage between the new booster and the original shot, although the FDA has cautioned they may be too small to support any conclusions.

The additional data could help encourage more people to get the booster. But since its authorization by the FDA in August, only 8.4% of those eligible for the shot have received it.

The slow uptake has made for greater uncertainty around future sales of both Pfizer’s and Moderna’s COVID-19 vaccines, which have earned the companies tens of billions of dollars in 2022. The U.S. government no longer plans to buy the shots in bulk in 2023, thereby shifting sales onto the private market. In response, both companies are considering a higher price, although executives have emphasized that people who are insured wouldn’t have to pay out of pocket.

Meanwhile, the Centers for Disease Control and Prevention is monitoring omicron’s prevalence in new COVID-19 cases, as well as the rise of several subvariants. According to recent estimates from the agency, the substrains BQ.1, BF.7 and BQ1.1 are gaining ground, with BQ.1 accounting for about 14% of new cases.

“In the next step and as part of our science-based approach we will continue to evaluate the cross-neutralization of the adapted vaccine against new variants and sublineages,” said BioNTech CEO, Urgur Sahin, in the companies’ Nov. 4 statement. “Our goal is to provide broader immunity against COVID-19 caused by SARS-CoV-2, including Omicron and other circulating strains.”

Pfizer and BioNTech will continue to evaluate the immunogenicity and safety of the bivalent shot in children between the ages of six months and 11 years in a Phase 1/2/3 trial.

Novavax on Nov. 8 disclosed results from a late-stage clinical trial testing updated versions of its COVID-19 vaccine, weeks after the data were originally expected to be available.

Study results showed a bivalent booster targeting the BA.1 and BA.5 omicron strains of the coronavirus failed to raise antibody levels by more than Novavax’s current vaccine or a monovalent vaccine aimed solely at BA.1.

The trial tested the three shots in adults aged 18 to 64 years old who were previously vaccinated with three doses of Pfizer’s or Moderna’s COVID-19 vaccines. It sought to determine whether the two redesigned Novavax booster shots could raise antibodies against omicron by more than the company’s original version.

The booster shot aimed just at BA.1 did, raising antibody levels against that strain by more than the original candidate and meeting the study’s threshold for success. But the bivalent vaccine did not, nor did it perform better than the BA.1-targeting candidate.

Novavax’s statement did not contain specific data on how the reformulated shots performed against BA.5, but the company said neither produced a better immune response than its original prototype against that strain, which is currently the most prevalent in the U.S.

The vaccine company, which arrived on the U.S. market well behind Pfizer, Moderna and Johnson & Johnson, described the data as supportive of its existing vaccine and the “broad immune response” it generates.

“The data we've collected here supports the continued and future use of our current vaccines as a booster,” Filip Dubovsky, Novavax’s chief medical officer, said in a call with reporters Nov. 7. “The study achieved its strain change endpoint, allowing for various vaccines to be pushed forward if they're eventually needed.”

“We saw no benefit demonstrated for the bivalent vaccine utilizing our technology,” he added. “This may be different from other vaccine technologies.”

Novavax’s shot uses a more traditional vaccine technology than do Pfizer’s and Moderna’s, which rely on messenger RNA to generate an immune response to the coronavirus.

The Centers for Disease Control and Prevention in October said the Novavax shot could be used as an initial booster following primary vaccination for those who cannot or will not receive Pfizer’s or Moderna’s vaccine.

But the focus has shifted to second booster shots, specifically the new omicron-targeting vaccines from Pfizer and Moderna. Uptake of those boosters has been slow in the U.S., while fewer than 50,000 people have received Novavax’s currently authorized vaccine.

Dubovsky noted in the call that the restriction on use of the shot as only an initial booster has limited its uptake.

It is unclear how Novavax will proceed with its omicron-targeting booster candidates. Dubovsky said the company will continue studying the shots and gather antibody levels against other variants.

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By Catalent Biologics

The COVID-19 pandemic has posed major challenges to the pharma industry, including the pressing needs to compress the timeline to achieve regulatory approval and to proactively establish a global supply network capable of delivering billions of doses around the world. The challenges and risks associated with this undertaking are high, and it's all-hands-on-deck for the sponsor companies, contract providers, and suppliers who are collaborating and innovating to help combat coronavirus. 

We interviewed Bernie Clark, Vice President, Marketing and Strategy, Catalent Biologics, to learn about new vaccine developments and strategies in response to the COVID-19 pandemic.

What are the challenges associated with reducing vaccine development timelines?

Clark: One challenge is that you're taking everything from process development, small-scale clinical production, scale-up through process performance qualification (PPQ), stock build, and eventual commercial launch and compressing it down to months rather than years. It's unprecedented. The overlap of these manufacturing phases stresses the importance of innovation and collaboration between partners and having the experience necessary for rapid scale-up.

How is the industry addressing these challenges?

Clark: Typically, a sponsor company would plan for small-scale manufacturing to supply clinical trials, and as the vaccine progresses through the clinic, the sponsor would begin manufacturing scale-up in anticipation of commercial needs. But in order to meet the compressed timelines, sponsors are looking to remove commercial scale-up from the critical path, and they are investing at risk in capacity and resources as early as the pre-clinical stage to be ready to meet demand if the vaccine is approved. It is common for small/virtual biotechs and mid-sized pharma companies to partner with Contract Development and Manufacturing Organizations (CDMOs) to provide needed clinical and commercial-scale manufacturing. But to address this urgent public health crisis, even large pharma companies are looking for partners to help supplement their global networks. 

What should a vaccine developer look for in a partner to manage these unprecedented challenges?

Clark: Developers should look for partners who have the resources, experience, and proven track record in supplying safe and reliable products to patients. It is important a partner employs the necessary expertise, demonstrates a stable supply chain, and houses the technology capable of manufacturing millions to billions of vaccine doses. A manufacturing partner is there to help you avoid delays by leveraging proven processes based on proven protocols and quality systems, which is critical given such aggressive timelines.

How is Catalent maintaining operational continuity during the pandemic?

Clark: Catalent continues to leverage its expertise, credentials, and commitment to "patient first" to produce safe and effective pharmaceutical products in the midst of the COVID-19 pandemic. Early in the pandemic, Catalent was designated an essential business owing to our global manufacture and shipment of essential medicines. Catalent immediately looked to the health and safety of our employees and the continued reliable supply to our partners, and ultimately to patients. The company launched a COVID-19 response team of principal leaders who report directly to our CEO. Many employees began working remotely, and management introduced a range of measures for essential employees to reduce the risk of infection, including staggered shifts, enhanced social distancing, and further use of personal protective equipment. Visits to our sites have been closely controlled, and employee travel severely restricted. We continue to monitor the status of employees and operations and provide regular communications, including pertinent health and safety information, to all our employees. Catalent continues to partner with companies from small or virtual innovators to mid- and large- pharma, to supply their non-COVID-19-related therapies to patients as well. From early on, Catalent surveyed deep into our supply chain looking for risks, delays, or concerns that could impact ongoing obligations to production and clinical supply. We continue to monitor vendors and have built stocks as a precaution where necessary.

How is Catalent contributing to COVID-19 treatments and vaccines?

Clark: Catalent is partnering with multiple companies in the development, manufacturing, and supply of over 50 programs related to COVID-19 vaccines, antivirals, diagnostics, and treatments, including Johnson & Johnson, AstraZeneca, Moderna, Humanigen, Arcturus Therapeutic, Spicona, Ennaid Therapeutics, and ViralClear. 

Catalent is also working with sponsor companies to repurpose drugs that are already approved or in clinical trials to determine if they may be effective in improving the outcome of patients with COVID-19.  Repurposed drugs can advance much quicker to patients, and that aspect has special relevance in fighting a pandemic.

Conclusion

Catalent continues to put the "Patient First" and do everything possible to keep our employees safe and healthy while reliably delivering for our customers. Our focus on innovation, flexibility, and collaboration allows us to solve problems creatively while adhering to industry norms and enable our partners to rapidly develop and manufacture COVID-19 vaccines and treatments while simultaneously continuing to provide other critical medicines to patients.

Pfizer is considering hiking the price of its COVID-19 vaccine by roughly four times what it currently charges as it prepares for sales in the U.S. to shift from government contracts to the private market.

The pharmaceutical company is targeting between $110 and $130 per adult vaccine dose after that transition, said Angela Lukin, Pfizer’s head of global primary care and U.S. president, on an analyst and investor call Oct. 20.

“We feel confident that this range will be seen as highly cost effective and definitely one that will help to enable and ensure appropriate access and reimbursement to the vaccine,” Lukin said on the call. Discussions with insurers are still in early stages, she added.

In recent contracts with Pfizer, the U.S. government has been paying an effective price of around $25 to $30 a dose for the company’s vaccine, which remains the most widely used of the available options in the country. However, with federal COVID-19 funds drying up, the Biden administration has planned to stop buying vaccine doses in bulk and shift distribution to the private market, likely by early 2023.

Lukin said that Pfizer expects people with government insurance like Medicare and Medicaid, or who are covered via commercial plans will not have to pay out of pocket to get vaccinated.

The pricing described by Lukin is higher than what investors have been expecting, according to analysts from SVB Securities and Cantor Fitzgerald, and above the $64 to $100 per dose range previously sketched out by competitor Moderna in September.

Shares in Pfizer climbed by more than 4% in the morning Oct. 21, while Moderna stock jumped nearly 6%.

The price hike could open up Pfizer to new criticism of its vaccine pricing, which has remained an issue throughout the pandemic even at the prices it currently charges for government sales. Umer Raffat, an analyst at Evercore ISI, called Pfizer's plans "a mistake," noting that, while such a move makes it more likely the company meets Wall Street estimates, it is "clearly bad optics.”

On the call, Lukin defended Pfizer’s planned pricing as cost effective for the vaccine’s value. She also said the transition to private market sales would mean higher costs as the company switches to a single-dose vial and handles commercial distribution.

“While a commercial marketplace presents new complexities,” Lukin added, “we are confident we have the capabilities to make this transition successful.”

Pfizer earned more than $22 billion from sales of its COVID-19 vaccine, branded as Cominarty, over the first six months of 2022. It has forecast annual sales reaching $32 billion in 2022.

But the company, as well as rival Moderna, face slowing demand for shots in the U.S. According to data from the Centers for Disease Control and Prevention, fewer than 20 million people have received either company’s updated booster shots, which are reformulated to better protect against the omicron variant. Less than one third of children between ages 5 and 11 have completed their initial two dose series, while only 3.5% of children aged 2 to 4 years old have.

Pfizer’s Lukin said the company is planning to support commercial marketing with communication through TV, radio, digital and social channels about booster dose eligibility and the importance of staying up to date on vaccination.

Moderna on Nov. 3 cut its sales forecast for its COVID-19 vaccine as third quarter revenue fell short of analysts’ expectations.  

In a quarterly earnings report, Moderna said its vaccine, known as Spikevax and the biotechnology company’s only marketed product, generated $3.1 billion in sales over the last three months. Those numbers came in below projections that Wall Street analysts had already reduced from $4.4 billion to $3.3 billion over the last month. 

Moderna also trimmed its vaccine sales projections for the year, cutting a prior estimate of $21 billion to between $18 and $19 billion. Multiple countries have deferred vaccine contracts into next year, resulting in anywhere from $2 billion and $3 billion in revenue that won’t be received this year, Moderna said. 

Moderna’s earnings are in contrast to Pfizer, which increased its vaccine revenue forecast by $2 billion when it reported earnings last month. Pfizer now expects $34 billion in annual sales from its shot, Comirnaty, after the vaccine generated $22 billion during the first half of the year.

Both Moderna and Pfizer are preparing to sell their vaccines in the private market, as the U.S. government doesn’t plan to continue the bulk purchases that have turned the shots into some of the industry’s most lucrative products. They’re doing so as demand for COVID-19 vaccines has cooled amid a slow rollout for the new booster shots tailored to versions of the omicron variant. 

Pfizer has already said it may hike the price of its shot to between $110 and $130 per dose, nearly four times its current price tag. Angela Lukin, Pfizer’s head of global primary care and U.S. president, defended the company’s plan on a recent conference call, noting that “people will not see any difference and the system will get the benefit of a cost-effective product.”

Lukin added that people covered by government and commercial insurance won’t have to pay out of pocket for the shots. 

Moderna hasn’t yet said what it will charge when vaccine sales move to the private market. In September, the company indiciated it was considering charging between $64 and $100 per dose. 

In a bid to expand its access to messenger RNA technology, CSL Seqirus on Nov. 2 agreed to a licensing deal that may be worth billions of dollars for San Diego biotechnology company Arcturus Therapeutics.

The CSL vaccine unit will pay $200 million upfront to license Arcturus’ technology and know-how to develop mRNA vaccines for COVID-19, influenza, pandemic preparedness and three other unspecified respiratory infections. Arcturus is also eligible for more than $4.3 billion in payments if certain developmental and commercial milestones are reached. 

CSL will take the lead on development and marketing, giving Arcturus a 40% net profit share for vaccines approved to fight COVID-19 and “up to double-digit” royalties on others, Arcturus said. The combination of expertise between the two companies may be especially helpful in offering a COVID-19 booster shot, CSL said in its own release.

Vaccine makers like CSL are eyeing the extraordinary success of Pfizer, BioNTech and Moderna in developing mRNA vaccines against COVID-19 in less than a year when the pandemic broke out.

CSL has seen some success with its own vaccine candidates in preclinical studies, but the deal with Arcturus gives the company access to technology that’s been proven on a larger scale. The COVID-19 vaccine developed by Arcturus using its self-amplifying mRNA technology succeeded in a pivotal study in Vietnam earlier this year and is now being evaluated as a booster.

Arcturus also recently received a vote of confidence from the U.S. government in the form of a $63.2 million grant. The Biomedical Advanced Research and Development Authority award doles out cash over three years to support the company’s work on a vaccine that could be used for rapid response to an influenza pandemic.

The CSL deal offers further validation of the Arcturus technology and improves chances for the eventual success of other experimental vaccines, Cantor Fitzgerald analyst Pete Stavropoulos wrote in a note to investors. “CSL is a well-established vaccine developer with an established global commercialization footprint,” he wrote.

CSL’s Seqirus unit is particularly active in flu vaccines. The company’s products include Fluad Quadrivalent for people aged 65 and older, a group that’s particularly vulnerable to the flu.

Moderna on Aug. 26 sued rival COVID-19 vaccine developers Pfizer and BioNTech, alleging that it pioneered and patented the messenger RNA technology used in their top-selling shot.

The suit, filed in U.S. and German courts, claims that Pfizer and BioNTech’s vaccine, known as Comirnaty, infringes on patents issued to Moderna between 2010 and 2016. 

"We are filing these lawsuits to protect the innovative mRNA technology platform that we pioneered, invested billions of dollars in creating, and patented during the decade preceding the COVID-19 pandemic," said Moderna CEO Stéphane Bancel, in a statement.

Moderna isn’t seeking to have Comirnaty removed from the market, or an injunction against future sales. Instead, the company wants compensation for all alleged use of its intellectual property by Pfizer and BioNTech in developed countries after March 2022.  

Early in the pandemic when vaccine supply was limited, Moderna pledged not to pursue patent claims in developed nations or any low- and middle-income countries. It recently changed that stance, however. While the company won’t ever pursue legal action in the 92 countries that are covered in the international vaccine alliance Covax, Moderna argued that vaccine supply hasn’t been a barrier to access for much of the world since March 2022.

Afterwards, the company “expected companies such as Pfizer and BioNTech to respect its intellectual property rights” and “consider a commercially reasonable license” from Moderna. “Pfizer and BioNTech have failed to do so,” the company said. 

Moderna believes Pfizer and BioNTech used its patent-protected technologies in two ways. One involves a chemical modification that both vaccines have and keep the shots from stimulating an unwanted immune response in humans. Moderna alleges its scientists began developing that modification in 2010 and, in 2015, were the first to test it in people. 

Moderna also claims Pfizer and BioNTech “copied” the company in designing a shot that teaches the body to recognize the full-length “spike” protein on the novel coronavirus. Moderna alleged that its scientists developed that approach when they created a vaccine for another coronavirus, Middle East Respiratory Syndrome, or MERS, years before the pandemic.  

These discoveries and other research “enabled us to produce a safe and highly effective COVID-19 vaccine in record time after the pandemic struck,” Bancel added, in the statement.

In a statement, Pfizer said it was surprised by the lawsuit because its vaccine was based on proprietary intellectual property owned by BioNTech. “We remain confident in our intellectual property supporting the Pfizer/BioNTech vaccine and will vigorously defend against the allegations of the lawsuit,” the statement said.

The history of intellectual property disputes among RNA drug developers suggests the lawsuit won’t amount to a significant payout, according to SVB Securities analyst Mani Foroohar. The most likely outcome “would be modest royalties paid by both companies, with little net favorable financial impact for anyone but the law firms involved," Foroohar wrote in a note on Aug. 26.

Moderna itself has been the target of lawsuits over vaccine-related intellectual property. Arbutus Biopharma and Genevant Sciences claimed that Moderna’s vaccine violated six of their patents related to the delivery technology involved in the shot. 

Meanwhile, the biotech also got in a dust-up with the National Institutes of Health over whether its scientists deserved to be named on a Moderna-owned vaccine patent.

Moderna and Pfizer remain locked in a race to get more vaccines to market. Both are seeking Food and Drug Administration authorization of updated booster shots that target the currently circulating versions of omicron.