PRNewswire (Apr 28, 10:12 AM) MERIDEN, Conn., April 28 /PRNewswire/ -- Protein Sciences Corporation, a world leader in developing the next generation of human and veterinary vaccines, announced today that a double blinded Phase II(b) clinical trial of FluBlOk(TM) met its two primary endpoints. The trial compared three different doses of FluBlOk, Protein Sciences' patented protein-based influenza vaccine that is produced using cell culture, with a standard dose of a licensed egg- grown influenza vaccine. Data analysis shows that FluBlOk was safe and statistically more immunogenic against the H3 influenza strain when administered at higher doses than the current licensed influenza vaccine. The H3 strain(1) causes the majority of the 20,000 to 50,000 excess influenza- related deaths each year in the U.S., more than 90% of which occur in the elderly. The trial was sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and conducted in 399 elderly subjects at three NIAID Vaccine Treatment Evaluation Units.
FluBlOk is like the licensed vaccines in that it contains antigens (hemagglutinin proteins) that are related to three strains of the influenza virus. However, its critical differences summarized below mean that FluBlOk presents a solution to a multitude of issues associated with egg-grown influenza vaccines. FluBlOk's antigens are manufactured through recombinant methods in cell culture. No eggs, live influenza viruses or biocontainment facilities are used in the development or manufacturing process. FluBlOk consists of three antigens stored in buffered salt water and does not contain preservatives such as thimerosal or adjuvants. New FluBlOk vaccines can be quickly and safely developed to address emerging pandemic viruses, as evidenced by Protein Sciences' achievement in developing and manufacturing a vaccine for the 1997 Hong Kong "Bird" flu in just eight weeks, and late appearing influenza viruses such as A Fujian in 2003-2004. In addition, FluBlOk represents a viable alternative to the licensed influenza vaccines for people who cannot take the licensed vaccines because of hypersensitivity to eggs or concern about thimerosal, a mercury-containing compound that is used as a preservative in most influenza vaccines.
The first clinical endpoint of the study was to show that FluBlOk is safe even at doses that contain up to nine times more active ingredient than the licensed egg-grown vaccines. FluBlOk was well tolerated at all dose levels and had a slightly lower rate of minor side effects than the licensed vaccine, which was also well tolerated.
The second clinical endpoint was to show that at least 20% more elderly subjects receiving high doses of FluBlOk achieve antibody levels that are believed to be associated with better protection against an H3 influenza virus than subjects receiving the licensed vaccine. Historically, 30% to 50% of elderly subjects vaccinated with the licensed vaccines achieve protective titers and therefore the goal was to show that 50% to 70% (20% more) of subjects vaccinated with FluBlOk would achieve protective titers. The groups receiving the two highest doses of FluBlOk exceeded the 20% goal -- 77% and 97%, respectively, of the subjects achieved protective titers. All groups vaccinated with FluBlOk achieved a higher Geometric Mean Titer (GMT), a common measure of vaccine effectiveness, than the group that received the licensed vaccine. The two higher dose groups had significantly higher GMTs, close to five times as high for the highest dose, and even the lowest dose had a 33% higher GMT than the group that received the licensed vaccine. A dose/response effect was shown in all groups. The study also showed that subjects who received FluBlOk achieved antibody titers against the normally less dangerous H1 and B influenza strains that were comparable to the licensed vaccine.
The trial was conducted in 399 elderly subjects (aged 64 to 89 years) and compared a licensed 2003-2004 egg-grown vaccine with three different doses of FluBlOk containing the same hemagglutinin antigens. The licensed vaccine contained approximately 15 micrograms of each of the three antigens and the three FluBlOk doses contained approximately 15 micrograms, 45 micrograms and 135 micrograms of each antigen, respectively.
The study was conducted by Dr. John Treanor (Principal Investigator), Dr. Robert Couch and Dr. Gilbert Schiff at the Vaccine Treatment and Evaluation Units of the University of Rochester, Baylor College of Medicine and the Cincinnati Children's Hospital Medical Center, respectively and was 100% monitored.
The Principal Investigator of the trial, John Treanor, M.D., Associate Professor of Medicine, and of Microbiology and Immunology, School of Medicine and Dentistry, University of Rochester stated, "We have recognized that there is a critical need to develop alternatives to egg-grown influenza vaccines for many years. The technology used for this vaccine is a promising step in this direction, and the finding of potentially enhanced immune responses in the elderly is an exciting additional bonus."
Drs. Manon M.J. Cox, Chief Operating Officer of Protein Sciences, stated, "We are very excited about these results and extremely grateful to NIAID for sponsoring the trial and the clinical investigators for their exceptional work under considerable time pressure. We and our advisors are convinced that the results clearly justify moving into Phase III, and we are gearing up to conduct a placebo-controlled field study this fall. Approximately 1,400 subjects have taken FluBlOk in six Phase I and II clinical trials that showed safety and efficacy in healthy adults and the elderly. She added, "We have decided to proceed with the 3x45 micrograms dose. However, because of the clear dose/response effect shown by the trial we will be evaluating lower and higher doses in various populations. In addition, because our manufacturing costs are projected to be at or below the licensed egg-grown vaccine and previous Phase I and II clinical trials show that the side effects of FluBlOk are significantly lower than the licensed vaccine we will pursue further testing in healthy adults because we believe we could have the product that will be attractive to this population, a market segment that has largely eluded the licensed egg-grown vaccines including FluMist(R)."
About Protein Sciences. Founded in 1983, Protein Sciences is a vaccine company focused primarily on using modern technology to make the next generation of safer and more effective human and animal vaccines. The Company has a pipeline of patented products that includes two influenza vaccines that have completed Phase II(b) human clinical trials, one of which, FluBlOk(TM) will enter pivotal Phase III trials in the fall of 2004, and a SARS vaccine and erythropoietin that have completed animal tests and will enter human testing soon. All products are recombinant proteins that are made using the Company's patented protein expression technology, the baculovirus protein expression system (BEVS), in which it is the world leader. Protein Sciences also has service businesses that are driven by its BEVS technology including GeneXpress(R) (developing and manufacturing vaccines, therapeutics and diagnostics for customers) and manufacturing and selling proteins related to HIV/AIDS, SARS, influenza and pandemic influenza for research use. The Company has developed all of its products and businesses internally and retains commercial rights to its major products. Website: http://www.proteinsciences.com/.
Background Information on Influenza and Influenza Vaccines
* Influenza is the most common cause of medically attended acute
respiratory illness in the U.S. often involving fever, chills, muscle
weakness, cough, sore throat, nasal congestion, headache and general
malaise.
* Up to 20% of the population in the United States becomes infected with
viral influenza each year. Field studies indicate the infection rate
ranges from a low of 10% in persons over age 65 to a high of 36% in
children aged one to eighteen. At the peak of a typical epidemic,
roughly 9% to 22% of all physician office visits are for flu-like
symptoms. Children are also a major factor in spreading influenza to
other population segments, including those at high risk of contracting
the disease. (2)
* According to the Centers for Disease Control and Prevention and the
American Lung Association, 20 to 50 million people are infected annually
in the U.S., causing 70 million lost work days(3) and 38 million lost
school days per year. The annual burden of the disease to society has
been estimated at $15 billion.
* Influenza is a serious disease resulting in an average of 110,000
hospitalizations and 20,000 to 50,000 deaths annually. Over 90% of
influenza-related deaths occur in people over age 65. More than 18,000
(>90%) of excess deaths (i.e., the number of influenza-related deaths
above a projected baseline of expected deaths) and approximately 48,000
of the pneumonia and influenza hospitalizations per year occur among
persons who are at highest risk for influenza related complications.(4)
Children under age five and women in the third trimester of pregnancy
are also at higher risk for serious complications.(5)
* Influenza related deaths can result from pneumonia as well as from
exacerbations of cardiopulmonary conditions and other chronic diseases.
A recent study has concluded that influenza plays a role in heart
attacks and stroke in the elderly and that influenza vaccination can
significantly reduce such diseases.(6)
Pandemics and Late Appearing Strains
* When new strains emerge, the consequences can be particularly
devastating. For example, the "Asian" flu's appearance in 1957 caused
approximately 70,000 deaths in the United States. During influenza
epidemics from 1969-1970 through 1994-1995, the estimated overall number
of influenza associated hospitalizations in the United States ranged
from approximately 16,000 to 220,000/epidemic. An average of
approximately 114,000 influenza related excess hospitalizations occurred
per year, with 57% of all hospitalizations occurring among persons aged
<65 years. Since the 1968 influenza A (H3N2) virus pandemic, the
greatest numbers of influenza associated hospitalizations have occurred
during epidemics caused by type A (H3N2) viruses, with an estimated
average of 142,000 influenza associated hospitalizations per year.
* In studies of influenza epidemics occurring from 1972-1973 through 1994-
1995, excess deaths occurred during 19 of 23 influenza epidemics
(unpublished data, Influenza Branch, Division of Viral and Rickettsial
Diseases [DVRD], National Center for Infectious Diseases [NCID], CDC,
1998). During those 19 influenza seasons, estimated rates of influenza
associated deaths ranged from approximately 30 to >150 deaths/100,000 in
persons aged > or equal to 65 years (unpublished data, Influenza Branch,
DVRD, NCID, CDC, 1998). From 1972-1973 through 1994-1995, >20,000
influenza associated deaths were estimated to occur during each of 11
different U.S. epidemics, and >40,000 influenza associated deaths were
estimated for each of 6 of these 11 epidemics (unpublished data,
Influenza Branch, DVRD, NCID, CDC, 1998).
* The CDC has estimated the possible effects of the next influenza
pandemic in the United States and analyzed the economic impact of
vaccine based interventions.(7) Using death rates, hospitalization
data, and outpatient visits, they estimated 89,000 to 207,000 deaths;
314,000 to 734,000 hospitalizations; 18 to 42 million outpatient visits;
and 20 to 47 million additional illnesses. Patients at high risk (15% of
the population) would account for approximately 84% of all deaths. The
estimated economic impact would be US$71.3 to $166.5 billion, excluding
disruptions to commerce and society. At $21 per vaccinee, CDC projected
a net savings to society if persons in all age groups are vaccinated. At
$62 per vaccinee and at gross attack rates of 25%, they project net
losses if persons not at high risk for complications are vaccinated.
Vaccinating 60% of the population would generate the highest economic
returns but may not be possible within the time required for vaccine
effectiveness, especially if two doses of vaccine are required.
Market for Current Licensed Influenza Vaccines
* Because of the low immunogenicity of existing vac cines, the potential
for side effects and the public perception that the vaccine is unsafe
and ineffective, the rate of vaccination is low, especially in high-risk
groups-the elderly and children-despite the fact that studies show that
annual vaccination even with traditional vaccines has significant
benefits that outweigh the risks for all age groups.(8)
* The U.S. Department of Health and Human Services set a national
objective of increasing influenza and pneumococcal vaccination levels to
> or equal to 60% among non-institutionalized, high-risk persons,
including those aged > or equal to 65 years by 2000.(9) This goal was
met for influenza vaccinations during the 199899 influenza season;
however, influenza vaccination levels may have reached a plateau.
* The total influenza market is approximately $1.5 billion annually
worldwide.(10) Analysts believe that the potential market for a modern
human influenza vaccine exceeds $4 billion annually for the right
product(11), and potentially twice that under certain conditions.
* The FDA estimates that approximately 80 million influenza vaccine doses
were administered in the United States in 2001. It is estimated that
approximately an equal number of doses were sold abroad. The CDC
estimates that 93 million doses of influenza vaccination were on hand
for the 2002-2003 season in the United States.(12)
* In the 2003-2004 influenza season:
* 83 million doses of vaccine were sold. Manufacturers plan to
produce 90 million doses for the 2004-2005 season but may reduce if
the orders do not come through.
* Aventis shipped 43 million doses of influenza vaccine in the United
States, giving it nearly 50% of the market.(13)
* PowderJect (Evans) (now Chiron) produced 38.6 million doses in
2003-2004, up from 25.6 million doses the year before. (14,15)
Chiron plans to produce 50 million doses for the 2004-2005 season.
* Wyeth, which departed the market in 2002, manufactured 24 million
doses (24% market share).
* Approximately 15% of the vaccine was not sold or administered in
2002-2003.
* Currently Aventis and Evans (now Chiron), both based outside the U.S.,
are the only suppliers of influenza vaccine to the U.S. market.(16)
MedImmune/Wyeth entered the market in 2003 but sales of FluMist(R) were
negligible.
Opportunities for Increasing the Influenza Vaccine Market
* The U.S. Advisory Committee on Immunization Practices (ACIP) recommends
that 185 million Americans should receive influenza vaccines (compared
to approximately 80 million who currently receive vaccinations),
including 83 million "at risk" individuals and 102 million who should be
vaccinated (health care personnel, household contacts with at risk
individuals and individuals aged 50-64) but excluding healthy adults
outside the target group (101 million) who may wish to be immunized. In
addition, a survey in the United Kingdom showed that almost one third of
those at risk from flu due to asthma or diabetes had never been
immunized.(17)
* A new national objective has been set > or equal to 90% influenza and
pneumococcal vaccination among the elderly by 2010, up 50% from the year
2000 target.(18) However, the CDC acknowledges that new strategies and
additional resources to implement adult vaccination activities may be
needed, including a modern vaccine.(19)
* Approximately 35 million persons in the United States are aged > or
equal to 65 years.(20)
* The U.S. Census bureau projects that the over 65 population in the
United States will grow as follows (in millions):
Year 65 and Over Population
2005 35,064
2010 37,387
2015 41,948
2020 47,338
2045 70,319
The United States ranks 32nd among nations with high populations aged 65
and older. Italy and Sweden rank first and second, and developing
countries are aging faster than developed countries. The world's
population age 65 and older is growing by an unprecedented 800,000
people per month.(21)
* Vaccination is recommended for persons aged 50-64 years because this
group has an increased prevalence of persons with high-risk conditions.
Approximately 43 million persons in the United States are aged 50-64
years, and 10-14 million (24%-32%) have > or equal to 1 high-risk
medical conditions (unpublished data, NIP, CDC, 2002). Influenza vaccine
has been recommended for this entire age group to increase the low
vaccination rates among persons in this age group with high-risk
conditions. Persons aged 50-64 years without high-risk conditions also
receive benefit from vaccination in the form of decreased rates of
influenza illness, decreased work absenteeism, and decreased need for
medical visits and medication, including antibiotics. Further, 50 years
is an age when other preventive services begin and when routine
assessment of vaccination and other preventive services has been
recommended.(22)
* There are 15-18 million adults aged 18-49 years and 8 million children
aged 6 months-17 years that have > or equal to 1 medical conditions that
are associated with an increased risk for influenza related
complications (unpublished data, NIP, CDC, 2002). Among children aged
04 years, hospitalization rates have ranged from approximately
500/100,000 population for those with high-risk conditions to
100/100,000 population for those without high-risk conditions. Within
the 04 age group, hospitalization rates are highest among children aged
0-1 years and are comparable to rates found among persons aged > or
equal to 65 years.
* Experts have concluded that very few of the 70 million children in the
United States under age 18 receive the annual influenza vaccine.
* Preparing for an influenza pandemic would require 280 to 575 million
doses of vaccine with a lead time of no more than four or five
months.(23)
FOOTNOTES:
(1) The H3 strain in the 2003-2004 influenza vaccine was A Panama and in
the 2004-2005 vaccine it will be changed to A Fujian.
(2) Prevention and Control of Influenza, Recommendations of the Advisory
Committee on Immunization Practices (ACIP), Morbidity and Mortality
Weekly Report (MMWR), April 12, 2002/ Vol. 51 / No 1. RR3
(3) Adams PF et. al. Current estimates from the National Health Interview
Survey, 1996 National Center for Health Statistics. Vital Health Sta.
10(200) 1999
(4) Updated recommendations from the Advisory Committee on Immunization
Practices in response to delays in supply of influenza vaccine for the
200001 season. Centers for Disease Control, MMWR 2000;49:88892
(5) American Medical Association ("AMA") website.
(6) Influenza Vaccination and Reduction in Hospitalizations for Cardiac
Disease and Stroke among the Elderly, Nichol K.L. et. Al., N Engl J
Med 2003; 348:13221332, Apr 3, 2003
(7) The Economic Impact of Pandemic Influenza in the United States:
Priorities for Intervention, Meltzer, M.I. et. al., Emerging
Infectious Diseases, Centers for Disease Control, Atlanta, GA, Vol. 5,
No. 5, September October, 1999.
(8) The New England Journal of Medicine October 6, 1995.
(9) Public Health Service. Healthy people 2000: national health promotion
and disease prevention objectives - healthy people 2000 review 1998-
1999. Washington, DC: US Department of Health and Human Services,
Public Health Service, 1999; DHHS publication no. (PHS) 99-1256.
(10) Financial Times "Antiviral Drugs and Vaccines, Technology and
Markets" 1996.
(11) The New York Times, January 31, 1997.
(12) AMA website.
(13) Aventis, Form 20F for the year 2002, p. 24.
(14) Med Ad News, p.4.
(15) Infectious Disease News, April 16, 2003
(http://www.infectiousdiseasenews.com/).
(16) Ibid.
(17) Med Ad News, January 2003, p. 4
(18) Influenza and Pneumococcal Vaccination Levels Among Persons Aged > or
equal to 65 Years United States, 2001, CDC, MMWR, November 15, 2002 /
51(45); 1019-1024.
(19) Updated Recommendations From the Advisory Committee on Immunization
Practices in Response to Delays in Supply of Influenza Vaccine for
the 2000-2001 Season. CDC Weekly, October 06, 2000 / 49(39);888-892.
(20) United States Census - 2000.
(21) An Aging World: 2001. U.S. Census Bureau and the National Institute
on Aging (NIA).
(22) ACIP recommendations for annual vaccination for people at high risk
from influenza are:
* Persons aged > or equal to 65 years (36 million);
* Residents of nursing homes and other chronic care facilities that
house persons of any age who have chronic medical conditions (39.5
million);
* Children and adults who have chronic disorders of the pulmonary or
cardiovascular systems, including asthma (12.5 million);
* Women who will be in the second or third trimester of pregnancy
during the influenza season (2 million).
* Children aged 6 to 23 months (5.5 million)
* Persons aged 6 months to 18 years who are receiving long-term
aspirin therapy and therefore might be at risk for developing Reye
syndrome after influenza;
* Children and adults who have required regular medical follow-up or
hospitalization during the preceding year because of chronic
metabolic diseases (including diabetes mellitus), renal
dysfunction, hemoglobinopathies, or immunosuppression (e.g., caused
by medications or human immunodeficiency virus).
(23) Department of Health and Human Services, FY 2004 Budget, Departmental
Magazine.
Protein Sciences Corporation
CONTACT: Manon Cox of Protein Sciences Corporation, +1-203-686-0800,Ext. 308
Web site: http://www.proteinsciences.com/
