By Bernarda Tundzhay, Reporter, London
Biopharmaceutical Report I
Novavax’s (NASDAQ:NVAX) NanoFlu influenza vaccine has garnered lukewarm expert predictions for its market uptake, with experts noting it does not seem to be a major improvement upon Sanofi’s (EPA:SAN) Fluzone.
Despite high expert and analyst expectations for positive Phase III results and subsequent FDA approval, NanoFlu’s similarity to Fluzone in terms of its components is a low bar for market advantage,
experts said. NanoFlu’s performance in the market will depend on other flu vaccines in the pipeline, with additional stiff competition from the long-entrenched Fluzone, experts added.
A price premium may be warranted if the Phase III demonstrates superiority, but the vaccine may run into higher costs anyway due to its production, experts noted. Novavax needs to offer discounts to secure a spot on the market, one expert said.
Experts expect that results from the Phase III will be consistent with the Phase II, which showed improved immune responses due to NanoFlu’s more efficient technology compared to traditional immune vaccine technology. The Phase II and Phase III use the same comparator, further underscoring expert expectations of positive data.
Top-line immunogenicity and safety data for the 2,650-patient, randomized, observer-blinded, active controlled Phase III trial (NCT04120194) are expected in 1Q20, according to analysts. A 27 June company press release indicated an upcoming licensure and future BLA via the accelerated approval pathway. Novavax did not return requests for comment.
NanoFlu’s peak sales were estimated at USD 783m globally, according to one analyst report. Novavax’s market cap is USD 111.36m.
Dampened market uptake expectations
As NanoFlu uses the same recombinant hemagglutinin(HA) protein nanoparticle as other flu vaccines, it is not a major improvement over what is already on the market, but rather it a me-too product, said Dr Peter Palese, chair, Department of Microbiology, Icahn School of Medicine, Mount Sinai, New York.
However, NanoFlu is unique in that it is produced in the SF9 insect cell baculovirus system, which is dissimilar to the traditional chicken embryo used for vaccines. While NanoFlu is an improvement in terms of production versus the current vaccines on offer(eggmade trivalent/quadravalent vaccines), that is a low bar for market success, a postdoctoral
Whether or not NanoFlu becomes the future influenza market leader will depend on the success of more revolutionary vaccines moving through Phase I/II trials, the scientist added. NanoFlu’s Phase II trial results have not been “mind-blowing”, as several
candidate vaccines have reported similar results, such as BiondVax’s (NASDAQ:BVXV) M-001, he said. BiondVax’s website states M-001 leads to an immune response in a wide range of influenza strains.
If M-001 does succeed, it would be the first universal vaccine, said Dr James Cook, clinical professor of Medicine, Division of Infectious Diseases, Loyola University Medical Center, Illinois. This would make it a major competitor for NanoFlu or other investigational vaccines, he added. M-001 has the theoretical advantage of being effective against a wide range of types of influenza and should not have to be reformulated each year to be effective against emerging influenza strains due to its design, said Cook. NanoFlu is likely to face the same problem regarding emerging influenza strains as any other vaccine made of antigens/protein sequences defined by known, circulating influenza strains, said Cook.
These vaccines might be less effective against a new strain that could emerge during the influenza season if that strain has mutations of one or more HA sequences, as occurred at the end of the 2018–2019 influenza season, said Cook.
Even if NanoFlu were to demonstrate superiority versus Fluzone in its Phase III, it would not automatically be a market leader, as Fluzone has been FDA approved since 1987, said Rhonda Simoff, vice president, Strategic Solutions, The American Journal of Managed Care. Fluzone costs USD 17 per 10 dose vial, and NanoFlu cannot be priced any higher than that, said Randy Vogenberg, principal, Institute for Integrated Healthcare and Access Market Intelligence, Greenville, South Carolina.
If NanoFlu does demonstrate superiority in its Phase III, which is designed as a noninferiority trial, it can add on a 25% premium, Simoff added. However, based on public information, it seems likely that NanoFlu will be more expensive than Fluzone to produce, thus leading to a higher sticker price, Vogenberg said. The typical range of drug discounts NanoVax can offer insurers for greater market access is 30–60%, Vogenberg said.
Positive Phase III, FDA approval expected
Experts expect the Phase III results will be positive based on Phase II data showing that NanoFlu demonstrated superiority against Fluzone with a 45% increase against
vaccine-homologous virus, A/Singapore (p<0.001), 22% increase against a historic drifted virus, A/Switzerland (p=0.014) and 42% increase against a forward drifted virus, A/Wisconsin (p<0.001).
The Phase III should have consistent results, as the technology used in NanoFlu is more efficient than the traditional immune vaccines technology, said Dr Amesh Adalja, senior scholar, Johns Hopkins Center for Health Security, Baltimore. Because the Phase III noninferiority benchmark will be passed due to the same comparator being used as the Phase II, FDA approval is likely, said Cook.
The trial’s 21–28 day primary efficacy endpoint timeframe is relevant to see the peak titer induced by the vaccine, Adjala said. After 28 days, the immune response would be expected to wane, he said. The saponin-based Matrix-M adjuvant of NovaVax’s NanoFlu demonstrated good tolerability in the Phase II, experts agreed, adding they expect a similar safety profile for the Phase III. There may be some mild adverse effects, such as shoulder pain or fever, Palese said, noting this type of vaccine is very unlikely to cause any adverse effects.
Bernarda Tundzhay Ahmed is a BSc Medical Physiology graduate from the University of Leicester and a recent MSc Finance and Accounting postgraduate. She has done excessive research in physiology and pharmacology, molecular and cellular pharmacology and neuroscience, mainly focusing on anticonvulsants and dopamine metabolism inhibitors in cocaine addiction treatments.