June 1, 2013 (Vol. 33, No. 11)

Improved Delivery, Adjuvants, Formulations, and Manufacturing among Innovations

The vaccines market is being driven by new antigens, delivery mechanisms, manufacturing methods, targets, and markets. As new entrants near commercialization, industry consolidation is likely, particularly in the adult vaccine segment. In the seasonal and pandemic vaccine market, competition remains stiff.

Frost & Sullivan forecasts a 9.6% CAGR for the European vaccines market through 2018, increasing from $6.36 billion in 2011 to approximately $12.05 billion in 2018. Pediatric vaccines comprise nearly 57% of that market, but the emerging adult vaccines market will likely grow faster, at a CAGR of 11% between 2011 and 2018.

Transparency Market Research estimates the U.S. vaccine market was valued at $12.8 billion in 2012, and predicts a 5.3% CAGR through 2018. Those figures, however, also include animal vaccines (which account for about 20% of the market).

“Nearly 90 percent of new (therapeutic) vaccines are based upon new antigens for dreadful diseases, and the remaining 10 percent include vaccines with new combinations of antigens,” noted Aiswariya Chidambaram, life sciences senior research analyst, Frost & Sullivan.

Such advances are differentiators. In Europe, for example, 22% of vaccine R&D projects include innovations in delivery mechanisms, adjuvants, formulations, or manufacturing methods.

“The expected approval and launch of potential vaccines such as GSK [GlaxoSmithKline]’s Mosquirix™ (malaria), Vaccinogen’s OncoVax® (cancer), Dendreon’s Provenge® (prostate cancer), and Diamyd Medical’s Diamyd® (diabetes) during the next five years is likely to fuel the growth of the European vaccines market significantly,” Chidambaram told GEN.

Within that same time frame, pneumococcal, meningococcal, and influenza vaccines are expected to experience “significant growth rates, driven by unmet medical needs,” she added.

Vaccines are in development for cancer, HIV, and diabetes, as well as malaria, tuberculosis, hepatitis, and even cognitive disorders and allergies. “An increase in the price for vaccines is also expected,” Chidambaram reported.

Almost 90% of new therapeutic vaccines are based on novel antigens for serious diseases, while the remaining 10% include vaccines with new combinations of antigens. [Capifrutta/iStockphoto]

Innovators Arise

The need for big pharma pipeline expansion is a driving force for therapeutic vaccines, triggering mergers and partnership agreements, Chidambaram said. “The European and global vaccines markets are ripe for consolidation, owing to high costs and entry barriers for small participants and technology providers, which propel them to partner.”

For example, in December, Vivalis and Intercell announced plans to merge and form Valneva. “Completion is expected in May,” according to Reinhard Kandera, Intercell CFO. The resulting company’s combined strengths in vaccines and antibodies are expected to make it a solid contender in the therapeutic vaccines market.

The pediatric version of Intercell’s Japanese encephalitis vaccine received European approval this February. An adult version of this cell culture-derived product is already marketed to travelers. “We see 1 to 1.5 percent market penetration, and are aiming for 2.5 percent by mid-2015,” Kandera explained.

A vaccine for Pseudomonas aeruginosa is in Phase III trials and another, for Clostridium difficile, is in Phase I. The company also has three clinical trials for tuberculosis underway with partners.

Bavarian Nordic has eight vaccines in development targeting cancer and infectious disease, according to Anders Hedegaard, president and CEO. “The lead, Prostvac®, targets advanced prostate cancer and is in Phase III trials,” he said. This vaccine is administered after hormone therapy but before chemotherapy. With 550 patients treated to date, Prostvac appears to extend average survival to about 25 months, up from 16.6 months. The Prostvac platform also is being assessed for breast, lung, and ovarian cancers.

“We also have a smallpox vaccine in development for the U.S. government,” Hedegaard added. “Approval is pending in Canada and the EU.”

Dendreon focuses on activated cellular immunology, having developed Provenge as a treatment for metastatic castrate resistant disease. “In patients with prostate specific antigen scores of less than 22.1, we saw overall survival rates 13 months longer than those for patients treated with other therapies,” explained John Johnson, chairman and CEO. Direct-to-consumer advertising is scheduled to begin this quarter.

Emergent BioSolutions focuses on anthrax and tuberculosis vaccines. A Phase II trial began in January for NuThrax™, an anthrax vaccine adsorbed with CPG 7909 adjuvant. According to Daniel Abdun-Nabi, CEO, he expects his firm will release data from a different, Phase Ib, tuberculosis trial this spring. “In 2016, the company plans to transfer its operations to a new manufacturing facility featuring single-use bioreactors,” Nabi added.

“Our anthrax vaccine generates approximately $220 to $230 million in revenue. Total 2012 revenue projections range between $280 and $284 million,” he continued. “We have a contract with the U.S. government to supply nearly 45 million doses through 2016.”

Dynavax Technologies is focusing on Heplisav™, an adult hepatitis B vaccine. “European regulatory review is on track,” noted Dino Dina, M.D., CEO. Approval is considered likely, he said, with a potential PDUFA filing expected soon.

Dr. Dina reported that Heplisav has demonstrated immunogenicity with fewer injections and over a shorter period. He estimated the market for adult hepatitis B vaccines to be around $270 million now, and could be $360 million once Heplisavis is approved. “When diabetics are included, the potential market represents approximately $750 million annually,” he said.

Seasonal and Pandemic Vaccines

The seasonal influenza market is dominated by well-established pharma companies that have approximately 10% of the total market each, according to Ramya Kartikeyan, Ph.D., head of infectious diseases for market analyst GlobalData. “Vaccines have been a prophylactic option for years, which makes the space somewhat more mature than some other infectious disease indications, like HIV,” she said.

Globally, the major prophylactic vaccines providers are Sanofi, GSK, AstraZeneca (MedImmune), Novartis, and CSL Biotherapies, Dr. Kartikeyan reported. A few small, indigenous players are also present. “However,” she added, “new players are poised to enter this competitive space with new vaccines, such as those using recombinant DNA technology.

“The main innovations in this space currently are the development of quadrivalent vaccines, new manufacturing methods, new routes of administration and adjuvants that elicit stronger responses,” Dr. Kartikeyan said.

Quadrivalent Vaccines

GSK and AstraZeneca already have approval and will introduce quadrivalent influenza vaccines in the U.S. and/or European marketplace within the next two years, Dr. Kartikeyan reported. When that occurs, they are expected to usurp trivalent vaccines, which currently account for annual global sales of $2.3 billion. By 2012, annual global sales are expected to approach $3 billion.

As Dr. Kartikeyan explained, adding an extra type B strain to trivalent vaccines increases protection for children, who are more susceptible than adults to type B strains. It also helps health authorities hedge their bets when selecting strains for seasonal vaccines. “It’s a step in the right direction,” Dr. Kartikeyan said, as the industry works toward universal influenza vaccines.

Market Differentiation

“These days, product differentiation is mostly set around offering immunity to at-risk populations or eliciting a stronger immune response through different routes of administration or adjuvants,” Dr. Kartikeyan explained.

“Innovative technology platforms that produce thermostabile, needle-less vaccines using microinjections and antigen-sparing adjuvants are likely to have a major impact on a company’s growth and market position,” Frost & Sullivan’s Chidambaram added.

Consequently, vaccines like AstraZeneca’s intranasal FluMist® and Sanofi’s intradermal Fluzone®, are projected to see rapid adoption. As Dr. Brad Tebbets, analyst, infectious diseases, GlobalData, elaborated, “AstraZeneca has established FluMist as the vaccine of choice for children over two years of age in the U.S. It launched in Europe last year as Fluenz, and received a U.K. contract for a mass vaccination program for two to 17-year-olds. That contract is set to begin in 2014.”

To target the elderly, “Sanofi created Fluzone High-Dose, a Fluzone variation vaccine containing higher concentrations of viral subunits to obtain a stronger immune response,” Dr. Kartikeyan said. Novartis’s solution, Fluad®, uses an adjuvant to similarly stimulate a stronger immune response among the elderly.

Nontraditional Manufacturing

In January, Protein Science’s FluBlok® became the world’s first recombinant influenza vaccine, developed using insect cell culture. Currently approved for people between 18 and 49 years old, approval for all persons 18 and older is expected later this year. Limited supplies are available now, with full availability anticipated for the 2013/2014 flu season.

Novavax has taken another approach, combining insect cell culture and recombinant baculovirus protein nanoparticles, to produce influenza vaccine candidates. The company is targeting seasonal and pandemic flu, as well as respiratory syncytial virus, SARS, malaria, and rabies.

Astellas is in late-stage clinical trials for its recombinant H5N1 influenza vaccine, ASP7373. The vaccine is being produced by cell culture, using the baculovirus expression vector system developed at the University of Minnesota.

In November 2012, Novartis’ Flucelvax® became the first mammalian cell-based flu vaccine approved by the FDA. GSK, Astellas, Sanofi, Baxter International, and AstraZeneca also are developing nontraditional manufacturing methods.

As next-generation vaccines mature, Chidambaram said, “they are likely to provide huge cost-savings and therapeutic benefits, and can significantly reduce vaccine development time.”

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