Last part.
) Group A Strep:
This disease is pervasive, causing an estimated 25 million cases of suspected illness in the U.S. alone, each year, according to the NIH. It is the second leading cause of pediatric visits, and is substantially a pediatric disease. Almost all cases are either 'strep throat', or impetigo (relatively minor skin infections). Prognosis is good, and antibiotics are the prescribed treatment. Most symptoms resolve themselves within a week. However, Group A Strep(GAS) also causes illnesses with potential devastating consequences that can even prove fatal, these include: the 'flesh eating' disease, rheumatic fever, toxic shock syndrome, and scarlet fever, ect.. Serious, or invasive illnesses, account for an estimated 10,000 cases in the U.S., per year, according to the C.D.C.. Other complications from GAS infection can include: otitis media, sinusitis, mastoiditis, and peritonsillar abscess, and pneumonia. In the developing world, 25% of all cardiovascular disease has been attributed to Group A Strep. In India alone, 6 million children suffer from rheumatic heart disease.
The Case For a Strep A Vaccine:
1) The magnitude of the illness which again causes an estimated 25 million cases of suspected disease in the U.S. alone, according to the NIH. It is the SECOND leading cause of pediatric visits, and is mainly a childhood disease. This makes it a pervasive, and potentially preventable illness, within an age defined target group. Currently there is no vaccine.
2) The SOCIOECONOMIC impact of this disease. The direct costs of diagnosing, and treating 'strep throat', each year, in the U.S. ALONE, is estimated to be approximately US$2 billion according to the NIH. This does not include lost productivity, which since the disease can run for days, with clinically significant symptoms, is substantial. Moreover, since it is recommended patients avoid going to work, or school, for 24 hours after beginning antibiotic treatment, this not only affects working adults stricken with Strep A directly, but also those adults who may have to stay home from work, to take care of a sick child. The socioeconomic costs of serious GAS complications can be life long, substantial, and seriously affect family systems, as they take health, and even lives.
3) The fact that GAS is substantially a CHILDHOOD ILLNESS. The ability to prevent childhood illness is looked upon more favorably by decision makers.
4) According to the NIH's Jordan Report 2000, there has been a RESURGENCE in serious GAS infections, often with complications, even among the healthy.
5) A vaccine could yield a significant REDUCTION IN THE USE OF ANTIBIOTICS, on the order of billions of pills over time, thereby helping to reduce the development of antibiotic resistant microbes. By reducing the number of bacterial throat infections, it is also hoped society can reduce the number of antibiotics inappropriately prescribed when a patient has a viral infection, and antibiotics are of no use. The number of patients contributing to the development of antibiotic resistance by not taking their full prescription should also decrease.
6) GAS infections RESISTANT to treatment by the current antibiotic of choice, for those allergic to penicillin, have also now been found in several parts of the world, according to the NIH, raising increased FEARS of 'superbugs'.
7) Since the classroom is viewed as an 'incubator' for this illness, and acts to spread this disease throughout the rest of society, strategy of inoculating children could significantly reduce all Strep A illness throughout society.
8) Health care priorities. Financial constraints on health care systems are very evident. This may increasingly be the case with the aging of the 'baby boomers', and as new medical technologies become available. Given Strep A is substantially an illness that causes 'sore throats', and skin infections, it would be prudent to free up health care resources, for more important needs.
Further supporting evidence concerning the need for a Group A Strep vaccine comes from the NIH's phase I sponsorship, and funding, of IDB's vaccine, and from the NIH's long standing interest in trying to facilitate the development of a GAS vaccine. In a report by the Institutes of Medicine performed at the request of the NIH, the development of a GAS vaccine, given to infants, was judged 'favorable'. The model was quantitative, and took a "cost-effectiveness approach that makes it possible to compare potential new vaccines on the basis of their anticipated impact on morbidity and mortality and on the basis of the costs for health care, costs for use of the vaccine, and costs for vaccine development," according to the report.
The Science:
Dr. Fran A. Rubin, program officer for group A strep at the National Institute of Allergy and Infectious Diseases, NIH: "We think the science has moved to the point where for the first time in many, many, years we have the potential for a safe and efficacious vaccine." New York Times, July, 1999.
ID Biomedical's Group A Strep vaccine was licensed from the University of Tennessee, where work towards it began approximately thirty year ago. It is based upon the M protein which has been the most sought after target concerning the creation of an effective GAS vaccine. It is responsible for GAS's resistance to immune system engulfment by phagocytosis. The most significant risk concerning the M protein is believed to be the potential production of cross-reactive antibodies. These can potentially cause damage to human organs and/or tissues, and are believed responsible for past GAS vaccine clinical trial failure that resulted in rheumatic fever. The last GAS vaccine trials were conducted approximately 20 years ago, and contributed to a 1979 FDA ban on the license for use of any GAS vaccine. This is the only ban of its' type by the FDA, and is still in effect; however, in a New York Times article from last year, Dr. William M. Egan, acting director of the agency's office of vaccines said: "It probably should be deleted."
Using modern biotechnology, previously unavailable, ID Biomedical hopes to surmount the hurdle of cross-reactivity and alas bring to market a vaccine sought after for decades. In pre-clinical animal studies its' vaccine was shown to produce no evident cross-reactive antibodies while at the same time eliciting those antibodies required for protective immunity. Again, protective immunity was established without any evidence of cross-reactive antibodies. As a further precaution, the antibodies produced were further tested upon certain human organs of cadavers with no evident binding, and therefore, it is believed, ability to cause damage. This preclinical evidence, in conjunction with FDA human clinical trial results to date, which are consistent with preclinical results, speak very highly of the future for this vaccine. Not only does ID Biomedical appear to have overcome the single biggest risk in developing a GAS vaccine, but it has also proven its' vaccine capable of producing the antibodies required for protective immunity in humans. Moreover, all tested subjects produced the required antibodies at a low dose(50 ug). Given the 200 year history of infectious disease vaccines, the thirty years of work on this vaccine, the 50-70 years of research upon Strep A vaccines, the considerable understanding concerning the immunology of Strep A, the good animal models available, the case for this vaccine is very impressive. One should also note that the immune reaction of this vaccine mimics natural infection, further decreasing assumed risk. As a final measure of safety, since ID Biomedical's vaccine is a sub unit vaccine(ie. made up of only a portion of the disease causing organism), it is viewed as safer by the part not used. Whole organism vaccines can potentially cause the same disease they are trying to prevent, and/or, cause the same side affects. Trials are now underway at the 100 ug dosage in conjunction with the NIH, under the FDA. This is to be followed by the 200 ug dosage. Trials using the 26 strain vaccine are anticipated to begin shortly in Canada, and are expected to run concurrently with the 6 strain vaccine trial completion. This should allow for trials on children with the 26 strain vaccine to begin this fall
Concerning efficacy, ID Biomedical's vaccine it is based upon a variable portion of the M protein, not a portion common to all strains. The current vaccine in clinical trials targets only 6 strains. A 26 strain vaccine is undergoing preclinical testing. There are over 100 different strains of GAS. However, since only relatively few of these strains are believed to account for the vast majority of illness, and these strains are relatively stable, unlike the flu, ID Biomedical's vaccine is seen as potentially very effective preventative. In fact, as measured by C.D.C. data, ID Biomedical's 26 strain vaccine is currently 'programmed' against greater than 90% of 'strep throat' infection, and over 95% of invasive disease in the U.S.. Furthermore, it can be programmed against differing strain frequencies in different geographic locations, or in different times, just as the flu vaccine.
MARKET POTENTIAL:
The market for this vaccine is potentially substantial and could be in excess of US$1.5 billion, per year, assuming three inoculations at US$25 per dose, or US$75 in total. This deemed potential is based upon the success of the Hepatitis B vaccine, and studies that have been done specifically with regard to a Strep A vaccine. Given current vaccine prices for vaccines like Prevnar(for Pneumococcus), which is selling for about US$58 per dose, for a four dose regime, or US$232 in total, ID Biomedical's GAS vaccine could have even more potential. Furthermore, if a universal recommendation by the American Pediatric Society is achieved full market penetration can be achieved relatively fast. A recommendation can happen even prior to final FDA approval. It is ID Biomedical's intention to advance this vaccine significantly further through clinical trials before partnering. This should increase the royalty received by ID Biomedical, upon licensing. The royalty rate achieved could be anywhere from 15%-50% plus milestone payments, depending upon a variety of variables. Aviron received a 40% royalty, plus US$400 million in milestone payments for its' flu vaccine, FluMist. Given the cash, and resources, ID Biomedical currently has, it's well positioned to advance this vaccine into the foreseable future. It could be on the market within five years.
COMPETITION:
The NIH lists seven other GAS vaccine approaches in development, including IDB's. Several vaccines have been licensed to commercial interests. The only one to make it past the FDA, and into trials, is ID Biomedical's, which received FDA approval over one year ago, on June 9, 1999. This potentially gives ID Biomedical a significant lead to market relative to the competition, and ability to establish itself first as 'the standard of practice.' This can make it harder for other vaccines to gain market share, should they make it through trials. Given the NIH selected ID Biomedical's vaccine for phase I trial sponsorship on October 27, 1997, and has selected no other since, despite it assisting other vaccine candidates as part of its' Strep A vaccine development program, there is further reason to be confident in IDB's science. ID Biomedical's vaccine is also increasingly proven in humans, while the other candidate vaccines are still speculative in this regard, and appear, as yet, to still have preclinical issues-- this widening gulf could increasingly marginalize some. For more information on Strep A vaccines in development please consult the NIH's Jordan 2000 Report at the end of this report.
II) Tuberculosis:
This is currently the leading killer of all infectious diseases worldwide, and is the leading infectious killer of women of reproductive age. It is highly infectious and spread through the air. It takes an estimated three million lives per year according to the CDC, and is expected to infect an estimated 300 million worldwide according to the NIH, within a decade. 90 million of these cases are expected to become active infections. It is a significant problem with AIDS patients due to their suppressed immune systems, and is significantly a disease of poverty. This plague is increasingly resistant to treatment, and these multi-drug resistant strains are spreading worldwide, raising increasing fears in policy makers. Costs of treating multi-drug resistant cases can be as high as US$250,000, per case, making this illness a significant financial threat. TB has been declared by the World Health Organization a "global emergency". Increasing, and strengthening, calls by the world's wealthy nations are being voiced concerning the need for an effective preventative TB vaccine. According to the C.D.C.:
"In both human and economic terms, prevention of tuberculosis is preferable to treatment of the disease. An effective vaccine strategy is justified in the US by projected reductions in risks for disease from global travelers, treatment costs, patient care costs and program costs. An investment of $800 million over 20 years to develop an effective vaccine would approximate the cost of control and treatment of tuberculosis in the US for a single year, currently estimated to be $700 million (Batelle study, 1995, Arch Int Med, 155:1595-600). The return in health benefits of a vaccine that is 80% effective in preventing tuberculosis over the next 50 years would be to prevent 135 million cases of tuberculosis and 40 million deaths from tuberculosis."
ID Biomedical's vaccine was licensed to Aventis Pasteur in 1995. They are one of the foremost forces in vaccines worldwide. At the time of the deal, it was the largest preclinical biotech deal in Canadian history, and was valued at about US$30 million. Before this deal was signed, the vaccine had demonstrated the ability to safely elicit protective immunity in animals. The following is an abstract on ID Biomedical's vaccine:
Author Horwitz MA ; Lee BW ; Dillon BJ ; Harth G
Address Department of Medicine, School of Medicine, U.C.L.A.
Proc Natl Acad Sci U S A, 92(5):1530-4 1995 Feb 28
Tuberculosis, caused by the intracellular pathogen Mycobacterium tuberculosis, is the world's leading cause of death in humans from a single infectious agent. A safe and effective vaccine against this scourge is urgently needed. This study demonstrates that immunization with the 30-kDa major secretory protein, alone or in combination with other abundant extracellular proteins of M. tuberculosis, induces strong cell-mediated immune responses and substantial protective immunity against aerosol challenge with virulent M. tuberculosis bacilli in the highly susceptible guinea pig model of pulmonary tuberculosis. Protection is manifested by decreased clinical illness including decreased weight loss, reduced mortality, and decreased growth of M. tuberculosis in the lungs and spleens of immunized animals compared with sham-immunized controls. This study demonstrates that purified major extracellular proteins of M. tuberculosis are candidate components of a subunit vaccine against tuberculosis and provides compelling support for the concept that extracellular proteins of intracellular pathogens are key immunoprotective molecules.
New Breakthrough: First Increase in Potency in 100 Years
Published online November 28, 2000
Proc. Natl. Acad. Sci.
Marcus A. Horwitz*, Günter Harth, Barbara Jane Dillon, and Saa Maslea-Gali
Department of Medicine, School of Medicine, University of California, 10833 Le Conte Avenue, Los Angeles, CA 90095
Tuberculosis (TB) continues to ravage humanity, causing 2 million deaths per year. A vaccine against TB more potent than the current live vaccine, bacillus Calmette-Guérin (BCG), is desperately needed. Using two commercially available strains of BCG as host strains, BCG Connaught and Tice, we have constructed two recombinant BCG vaccines stably expressing and secreting the 30-kDa major secretory protein of Mycobacterium tuberculosis (M. tb.), the primary causative agent of TB. We have tested the efficacy of the two strains in the highly susceptible guinea pig model of pulmonary TB, a model noteworthy for its close resemblance to human TB. Animals immunized with the recombinant BCG vaccines and challenged by aerosol with a highly virulent strain of M. tb. had 0.5 logs fewer M. tb. bacilli in their lungs and 1 log fewer bacilli in their spleens on average than animals immunized with their parental conventional BCG vaccine counterparts. Statistically, these differences were highly significant. Paralleling these results, at necropsy, animals immunized with the recombinant BCG vaccines had fewer and smaller lesions in the lung, spleen, and liver and significantly less lung pathology than animals immunized with the parental BCG vaccines. The recombinant vaccines are the first vaccines against TB more potent than the current commercially available BCG vaccines, which were developed nearly a century ago.
According to the vaccines' inventor this vaccine could enter human clinical trials this year. If successful it could ultimately become a universally mandated childhood vaccine. For more information please check the following link.
For some suggested clinical trial timelines for TB vaccines please check the following: Clinical Trial Timelines
For a more detailed account of TB, the need for a vaccine, as well as issues concerning the development of one, please consult the following authoritative document: Blueprint for Tuberculosis Vaccine Development.
III) AIDS:
This illness has quickly risen to become one of, if not the, most notorious infections of our time and currently infects approximately 35 million people world-wide. It slowly destroys the immune system and leaves its' victims vulnerable to opportunistic infections, and cancers. In just a couple decades it has taken an estimated 19 million lives. In 1999 alone another 5.4 million more became infected according to UNAIDS/WHO. But more than just an illness, this illness is emerging as a development and security crisis in sub-Saharan Africa, where most of those suffering live. In this region alone there were an estimated 4 million newly infected just this last year. 95% of world-wide AIDS cases occur in developing nations according to the NIH.
While organizations like the NIH view a preventative vaccine as the best solution for AIDS, discovering one has proven very difficult. Several fundamental issues remain from: the lack of a good animal model, to a solid understanding of the disease, to the HIV mutation rate, to a consensus clarity concerning how to solve these issues. Nevertheless, hope continues, and several different approaches are being backed, with substantial funding provided. Another factor that could help sustain development interest, according to the NIAID: "the World Bank and other philanthropic organizations are working on new ways to ensure a large, profitable market for the successful HIV vaccine.." While ID Biomedical's vaccine is being investigated as a possible preventative, and some researchers believe important clues could be obtained from a therapeutic vaccine concerning the development of a preventative, IDB's current focus is on the creation of a therapeutic vaccine. This would in effect act as an AIDS drug. Of special note, IDB's vaccine has already produced encouraging results in human, small-scale, phase I, trials. It should be approved for, and re-enter, expanded phase I/II human trials on 100 people shortly. This vaccine has been partially backed by the NIH. It is specifically designed to deal with the HIV mutation rate, which is believed to be the highest in nature, and is believed responsible for much of the failure of AIDS drugs. In fact, it is hoped, based upon actual evidence in humans, that IDB's vaccine can cause a substantial reduction in the HIV mutation rate, and thereby extend the longevity of current AIDS drug treatments. It also potentially makes a substantial impact upon a patient's viral load levels, and has reduced it as much as 95% in some individuals. It can also improve the immune system potentially. IDB's vaccine also appears safe, which is a significant issue for current AIDS drugs. It is composed of GP120 surface molecules from seven strains that are attached to an immune stimulating protein. It can be rationally programmed for different geographic areas based upon strain prevalence. As a therapy, in comparison to drugs, it may also only require one inoculation every several months, for instance, instead of taking a pill(s) every day. This could be important for treatment control purposes in many areas of the world, and help save costs. It should prove significantly cheaper than medications. This could help in many poorer areas of the world. Clinical trials are anticipated to take place at NIH affiliated sites, outside the U.S.. The inventor is Dr. Ayre Rubinstein. He is Professor of Paediatrics and Microbiology at Albert Einstein College of Medicine. Dr. Rubenstein is also a director of one of the NIH sponsored Centers for AIDS Research in the U.S.. His research has been given distinction, and awarded, by the US Secretary of Health. Biomira is currently able to manufacture this vaccine to the required trial standards. Currently IDB only has a Memorandum of Agreement on this vaccine. It intends to replace this agreement with a definitive licensing and collaboration agreement in the very near future. There are however many groups competing to be the first with an AIDS vaccine. There are believed to be 70 AIDS vaccines in development. Given the nature of this disease, this vaccine could meet with an accelerated approval process on compassionate grounds. It could be on the market within just a few years. According to a research report by Paradigm Capital this vaccine could eventually bring in US$1 billion, per year, in revenues.
IV) E. coli and Type III Secretion:.
While E coli is a natural part of the intestinal flora of both animals, and humans, some strains can cause illness, and worse. The E coli strain responsible for 'hamburger disease' is one such instance, and is constantly finding its' way into the headlines, as outbreak, after outbreak, occur as a result of contaminated food, or water supplies. 'Hamburger disease', also known as enterohemorrhagic E coli, is estimated to strike an estimated 20,000 individuals, per year, in the U.S. alone, according to the C.D.C.. It is also a significant cost borne by the food industry in terms of surveillance, and wasted food. Most importantly however, the frequency of this illness is believed to be increasing. According to Professor Mac Johnson of the Royal Veterinary College this strain is even starting to be found in pets; however, no instance of it being spread from pets to humans has yet been identified. According to the CDC, this disease "often causes severe bloody diarrhea and abdominal cramps; sometimes the infection causes nonbloody diarrhea or no symptoms. Usually little or no fever is present, and the illness resolves in 5 to 10 days. In some persons, particularly children under 5 years of age and the elderly, the infection can also cause a complication called hemolytic uremic syndrome, in which the red blood cells are destroyed and the kidneys fail. About 2%-7% of infections lead to this complication." Another strain of pathogenic E coli, called enteropathogenic E. coli, is a leading cause of childhood diarreah, and dehydration, world-wide, and takes an estimated 1,000,000 lives.
Whereas other vaccines in development for E coli infection target only specific strains, ID Biomedical's vaccine, based upon the work of Dr. Brett Finlay, of UBC, seeks to prevent E coli illnesses by targeting factor(s) common to different strains. This could potentially provide a more broadly based preventative. According to the NIH's Jordan 2000 Report, a vaccine just for 'hamburger' disease would have relatively limited usefulness due to its' relatively rare occurrence. "Such a vaccine could be useful during a community outbreak to prevent secondary spread or in an institutional or child care environment. If an intimin(or other shared antigens) response could be shown to protect against 'hamburger disease' as well as infection with closely related" enteropathogenic strains, "a stronger case for a vaccine strategy could be made.... particularly if it's shown to be a major cause of diarrheal disease burden in the U.S." Dr. Finlay's work has been published in leading scientific journals from Cell, to Nature, and he himself has been distinguished as one of Canada's leading young scientists. He is also a Howard Hughes Medical Institute, International Research Scholar. The mechanism underlying his work is called the Type III Secretion System, and it is being investigated by ID Biomedical as a potential platform technology for the oral delivery of vaccines, and drugs. "Any number of intestinal infections could be addressed this way," according to the company. If it works, this could prove the basis of a very significant product pipeline for ID Biomedical. IDB's E coli vaccine could be in trials within about 18 months. Since the Type III Secretion System is incorporated into this vaccine, trials upon it could also act as an important 'proof of principle' for this technology.
LINKS:
ID Biomedical's website
Prospectus, and recent financials-- Search ID Biomedical
NIH Jordan 2000 Report
Stock Symbols:
IDBE on the NASDAQ, National Market
IDB on the Toronto Stock Exchange |
