Global market growth for vaccines forecasted at 12%
( Edited version published in Genetic Engineering News Dec. 1, 2009)
The potential H1N1pandemic has drawn renewed interest in vaccines.
Vaccines over the last 100+ years have been one of the most important agents for controlling infectious disease beginning with smallpox then polio in the fifties. From a commercial standpoint vaccines have been a low growth business due to safety risks and low prices utilizing technology(virus grown in fertilized chicken eggs) that is ancient with frequent shortages. The production difficulties are more apparent with the current pandemic flu emergency and widespread shortages of H1N1 vaccine.
The recent wave of M&A deals involving vaccines (GEN Oct.15 Blogtech) show more interest by Big Pharma in vaccine products because it is more difficult to discover and get FDA approval for novel drugs. New technologies such as adjuvants, cell culture and engineered antigens now provide an evolving R&D base for novel immunotherapeutic products. And longer term there is the potential of genomics for sequencing organisms and developing immune boosters.
With all the focus on Pandemic Flu and its economical consequences governments and foundations believe vaccines are one of the most effective public health interventions. The Bill and Melinda Gates Foundation (www.gatesfondation.org) has been funding vaccine research since 1998 and committed $2B through 2009. Major developmental programs are for malaria, TB and HIV with a goal of preventing 4 million deaths per year. More than 200 million children have been immunized since inception.
The WHO (www.who.int) lists the following new vaccines that are at or near the commercial stage: Rotavirus, Pneumococcal disease, Human papillomavirus (HPV) and meningococcal meningitis A (Men A) so a significant rollout of new products is underway.
Several bullish forecasts for adult and pediatric vaccines have been published over the past two years.
Kalorama Information published a comprehensive report, Vaccines The World Market, in June of 2009 with profiles of companies and product forecasts. Kalorama reported global sales of $9.9B+ in 2008 for pediatric vaccines with growth forecasted at 16.3% annually through 2013 reaching $21.1B. Among the new pediatric products that will drive sales growth are hepatitis, MMR, combination and Pneumococcal vaccines. The Worldwide Market for adult vaccines was $9.2B in 2008 growing at 14% to reach $17.8B in 2013. New product growth is expected to come from cervical cancer (HPV), influenza, Pneumococcal, and hepatitis.
While Kalorama believes in the growth model they reiterate the lingering concerns about product safety, supply shortages and consumers’ reluctance to immunize.(There are plenty of vaccine opponents out there).
Datamonitor estimates the current market for vaccines by major players in the $19B range.
The leaders in order of market share are Merck, Sanofi, GlaxoSmithKline,Wyeth (Pfizer) and Novartis. Seasonal Flu sales for 2008/2009 are $2.8B growing to the $5B range by 2018/2019. VisionGain states in their Global vaccine Report,“The period of 2008-2013 will be one of the fastest growing segments of the pharmaceutical markets”. Scienta Advisors of Cambridge, MA in a recent report forecasts 12% annual growth from 2008 through 2014 with growth of 8% in the viral vaccine sector and 10% growth in the pediatric bacterial vaccine sector vaccines for meningitis and MRSA. Scienta cites new trends in the market such as fewer competitors and product innovation that translates to higher volume and margins for leaders.
Immunotherapeutic vaccines are also a huge commercial R&D focus for cancer but beyond the scope of this article (see GEN March 1, 2007).
Major Players are 90% of current vaccine sales
GlaxoSmithKline (GSK), Novartis and Astra Zeneca (AZN) have recently made major investments in vaccine products and technology. Leerink Swann estimated orders of $7B for swine flu from all players worldwide. The Wall Street Journal reported that GSK has invested more than $3.2B on R&D, acquisitions and manufacturing and one of the biggest bets on flu vaccines. GSK is also the leading developer of adjuvants starting with the $300M acquisition of Corixa in 2005. GSK markets over 25 vaccines worldwide with a broad pipeline of 20 vaccines for pediatric and adult diseases including herpes and flu. AstraZeneca (AZN) bought vaccine innovator Medimmune two years ago and now are selling the FluMist nasal spray products for seasonal flu A+B. Medimmune is a leader in pediatric health with its RSV vaccine. AZN has a number of collaborations with smaller companies for vaccine and immunotherapy development. Novartis (NVS) has a contract to supply 90 million doses to the U.S. with a recent switch from multdose to single dose due to U.S. consumer concern about the use of trace amounts of thimerosal, a preservative that contains mercury. Has aggressively invested in cell-based manufacturing technology for future vaccines with a $1B plant in Holly Springs N.C. in partnership with HHS, and is forecasting over $500M in sales for Q4. Sanofi-Aventis expects H1N1 sales of about $500M in Q4 and believes that its product can be delivered in one dose.
Immunostimulants have been under development for at least 20 years. Vaccines currently on the U.S. market primarily use aluminum salts but some of the newer vaccines outside the U.S. such as the H1N1 from GSK will use an oil-in-water emulsion and Vitamin E called ASO3. GSK’s Cervarix cervical cancer vaccine for HPV will use the GSK proprietary AS04 adjuvant consisting of an aluminum salt and MPL (monophosphoryl lipid A).
Novartis also has an adjuvant in its H1N1 vaccine called MF59, an oil-in-water emulsion, which can elicit a Th2 antibody response with a lower dose. Pfizer (Coley) and Idera (IDRA) have toll receptors under development for use as adjuvants .
Antigenics’(AGEN) QS-21 adjuvant is now in 15 clinical trials of which four are in Phase III trials. Licensees include GSK and Elan.
Datamonitor published an in-depth report in Q4 2008 called “Stakeholder Opinions: Vaccine Adjuvants uncertainty rule”,that reviews adjuvant technology for both prophylactic and therapeutic vaccines. Datamonitor sees a lower barrier for approval for therapeutic applications such as cancer and thinks that the GSK AS04 performance in the product will have a crucial impact on prospects for future “combination” immunostimulatory adjuvants.
Here are some of the significant new vaccine technologies under development for infectious disease by emerging companies:
Crucell focuses on vaccines and proteins utilizing its proprietary PER.C6 cell line and its AdVac vector technology that has an ability to mediate a strong T-cell immune response. Vaccines under development include Yellow fever, Flu, TB, Malaria, Ebola, Marburg and HIV. Among their strategic partners include Sanofi Pasteur, GSK, Novartis, and JNJ who recently purchased 18% of the Company.
CSL Ltd. (ASX.AX)
CSL is an Australian Company with a broad commercial vaccine product line including H1N1,the Gardasil partnership with Merck and has an extensive biological product R&D. New vaccine programs for Flu are partnered with Merck and Wyeth. The Company has been working on a proprietary adjuvant called Iscomatrix consisting of saponin, cholesterol and phospholipids and is currently in Phase II for Flu.
Inovio is focused on DNA vaccines utilizing SynCon construct technology and electroporation delivery that have both preventive and therapeutic capabilities. Its pandemic flu program is at the pre-clinical stage and the HIV Pennvax-B program is in Phase I.
Ligocyte is a privately held vaccine Company focused on VLP (virus-like particle) comprised of multiple copies of a protein antigen that mimic the native virus. The initial vaccine target will be Norovirus currently in Phase I and formulated with the GSK’s MPL adjuvant.
Novavax is developing recombinant vaccines for infectious disease including H1N1 using proprietary virus-like-particle (VLP) technology. VLP’s build a structure similar to the virus without the gene for replication and trigger a robust immune response. R&D programs include H5N1, RSV, VZV and HIV. The manufacturing process is expected to be higher yielding and less complex than current egg-based manufacturing.
Profectus is a VC funded private Company utilizing “prime boost” technology that delivers plasmid DNA followed by a recombinant Vesicular Stomatitis Virus vector. Viral disease targets include HCV, HPV, HSV-2 and HIV but none in the clinic yet.
PSC is a privately held vaccine Company that has over 25 years experience with a patented baculovirus expression vector system (BEVS) for production of vaccines and proteins. Its FluBlok seasonal influenza vaccine completed Phase III clinical studies and is under review at the FDA.
Vical develops vaccine and immunotherapy products based on DNA delivery technology and the Vaxfectin adjuvant currently in a Phase I trial for H5N1 pandemic influenza. A CMV Phase II trial is also underway for an immunotherapeutic vaccine . Vaxfectin is a cationic lipid formulation that enhances immune response to pDNA vaccines. The lead influenza candidate utilizes two highly conserved virus proteins –nucleoprotein (NP) and ion channel protein (M2)-plus an H5 surface protein.
Heavy R&D investment in vaccine technology over the past 10 years by government, non-profit and commercial organizations will result in new formulations, better delivery systems and new products to control infectious disease. Advances in cell culture and bioreactors combined with recombinant technology such as DNA and VPL vaccines will make manufacturing more cost effective and speed up introduction of new products. Adjuvants can boost the immune response and lower costs. As new vaccine products proliferate and technologies gain clinical and regulatory acceptance smaller innovative biotech companies will undoubtedly advance in the market.
Rod Raynovich www.raygent.com 12/1/09