BOCA RATON, Fla., March 21 /PRNewswire-FirstCall/ -- Nabi Biopharmaceuticals announced today that it will continue development of its Gram-positive program, led by StaphVAX(R) [Staphylococcus aureus Polysaccharide Conjugate Vaccine] and Altastaph(R) [Staphylococcus aureus Immune Globulin Intravenous (Human)]. Today’s decision was based on important conclusions from an outside advisory panel’s review of the company’s assessment of the StaphVAX confirmatory Phase III clinical study results. The assessment revealed marked differences in the effectiveness of the lot of vaccine used in this study compared to the lot used in the previous Phase III clinical study.
On November 1, 2005, Nabi Biopharmaceuticals announced that this study had failed to meet its primary endpoint. Because these results were not consistent with previous positive clinical data for StaphVAX, the company developed an investigation plan and formed an outside advisory panel of experts to conduct an assessment to determine the factors that led to the unexpected results. This panel was tasked with three main objectives: review and revise the plan; analyze the data; and provide direction for the future development of the company’s Gram-positive infections program.
In collaboration with the panel, Nabi Biopharmaceuticals reached two important conclusions related to the future development of StaphVAX and Altastaph:
1. The quality or functional characteristics of the antibodies generated by the vaccine used in the confirmatory clinical study was inferior to those antibodies generated by vaccine lots used in previous and subsequent clinical studies.
2. Medical factors associated with kidney disease in dialysis patients impaired their immune response to the vaccine. When considered in combination with an increase in the virulence of the bacteria, these factors also contributed to the observed lack of protection in this study population.
Thomas H. McLain, chairman, chief executive officer and president, Nabi Biopharmaceuticals, stated, “Today’s announcement marks a new beginning for our Gram-positive program, which is much enhanced by the knowledge we’ve gained about the bacteria and immune response. Moving forward, we have a clear development pathway on which to readily advance our vaccine and antibody products toward commercialization.”
Conclusion #1: Quality of Antibody Important to Confer Protection Against Bacteria
As background, the first Phase III clinical study used a vaccine produced at small scale in Nabi Biopharmaceuticals’ own research and development pilot manufacturing facility. The confirmatory Phase III study used a vaccine produced at large scale by a contract manufacturer. Subsequent bridging and immunogenicity clinical studies completed in 2005 used vaccine lots produced by a second contract manufacturer, Cambrex Bio Science Baltimore, Inc. (Cambrex). Nabi Biopharmaceuticals moved production to Cambrex because their facility was configured to be licensable for Europe.
The results of a series of experiments have demonstrated that the quality of the antibodies generated by the vaccine used in the confirmatory Phase III study was inferior to the antibodies generated by the vaccine manufactured by Nabi Biopharmaceuticals used in the first Phase III clinical study. This assessment was based on data from functional antibody assays and confirmed through a series of animal protection model studies. As an example, healthy animals dosed with the vaccines or with human antibodies generated from vaccines manufactured by Nabi Biopharmaceuticals were 100 percent protected from challenge against Type 8 S. aureus bacteria. In contrast, only 30 to 50 percent of the animals dosed with the vaccine or human antibodies from the lot used in the confirmatory Phase III study were protected against subsequent challenge with Type 8 S. aureus bacteria.
Also of significance, Nabi Biopharmaceuticals further substantiated this outcome through experiments using lots of vaccine produced by the second contract manufacturer, Cambrex. A series of clinical immunogenicity studies in dialysis and surgical patients, as well as healthy adults dosed with Cambrex-manufactured StaphVAX, were completed in 2005. Experiments using antibodies from patients in these studies demonstrated a protection benefit that was similar to the vaccine produced by Nabi Biopharmaceuticals. Animals dosed with these antibodies were 100 percent protected from challenge with the bacteria.
Next Steps: Build New Intellectual Property Position; Employ New Assay to Release Vaccine Lots
Data from the company’s review have defined subtle, but what are now understood to be significant changes in elements of the manufacturing process for the lot used in the confirmatory Phase III study. These changes resulted in differences in the capsular polysaccharide structure itself that are believed to be important for producing high-quality and high-affinity antibodies. Nabi Biopharmaceuticals is already engaged in the process of seeking to secure additional intellectual property rights as a result of these findings. The analysis of these factors will continue as we work in collaboration with a sub-group of the assessment panel, who are experts in capsular polysaccharide conjugate vaccines. As the company advances this new learning about the structure of vaccines to prevent Gram-positive bacterial infections, it will also seek to bolster its intellectual property position to protect the innovative mechanism of action common to its vaccine and antibody products under development.
It is also important to note that as part of completing this assessment, Nabi Biopharmaceuticals has developed a new laboratory assay capable of distinguishing these findings about antibody quality. This new assay will be used to ensure that future vaccine and antibody product lots generate antibodies of optimal quality prior to initiating additional clinical studies.
Conclusion #2: Optimal Protection Related to Virulence of Bacteria and Patients’ Immune System
As background, the level and functional activity of antibodies needed to achieve protection from infection is dependent on two factors, the virulence of the bacteria and the strength of the patient’s immune system. In designing a clinical study program in dialysis patients, it was widely understood that this was a difficult study population because of the underlying factors associated with kidney disease, including uremia and diabetes, which compromise the function of the human immune system. In addition, the ability of a vaccine to prevent infection in dialysis patients is made more challenging because they are at continuous and prolonged risk for infection. Because S. aureus bacteria often colonize at the dialysis access site, antibodies generated by a vaccine in these dialysis patients could be viewed as functioning more as a treatment of an active infection, rather than preventing a new infection. High levels of optimal antibodies in the first Phase III clinical study may have compensated for the virulence and the continuous challenge posed by the bacteria at the dialysis access site, as well as the impaired immune response in these patients.
The results from the confirmatory Phase III study indicated that these considerations were of even greater significance. The analysis of the bacteria from the confirmatory Phase III study supports that the virulence of the bacteria may have become even more significant in the period since the first Phase III clinical study was conducted in 1999 and 2000. In the confirmatory trial, these bacteria would be expected to have further weakened the function of the immune system in these patients through the release of higher levels of toxins. When combined with the sub-optimal quality of the antibodies generated by the vaccine used in the confirmatory Phase III study, these factors account for the lack of protection observed in this trial.
Clinical Development Program: Strategic Direction and Next Steps Working with the assessment advisory panel, Nabi Biopharmaceuticals has reached a series of decisions related to the future clinical development of its Gram-positive infection programs.
First, future vaccine and antibody development should incorporate additional antigens to the bacteria and to toxins released by the bacteria for the widest and best protection.
Second, future clinical studies of the vaccine should be focused on larger at-risk patient populations who are healthier and more immune competent.
Third, development of antibody products should advance more rapidly, focused initially in treating patients with active infections, and preventing infection in high-risk, but healthier groups, in the hospital.
Finally, the factors related to the bacteria and the infections caused by the bacteria from this assessment have underscored the need for a continuum of care options for patients at risk for Gram-positive bacterial infections. Vaccines can be used to prevent infection and recurrence of infection in patients at long-term risk. Antibody products are needed to prevent infection in patients at immediate risk and to treat healthcare-associated bacterial infections, which continue to increase. The panel affirmed the importance of both vaccine and antibody products to combat these infections.
Mr. McLain continued, “Hospital- and community-associated bacterial infections continue to represent serious public health challenges. Our unique knowledge base and experience in this area has been strengthened by what we have learned from the confirmatory Phase III study analysis and our work with this respected panel of objective experts. Over the last four months we have expanded our understanding of the bacteria itself; advanced our knowledge about the manufacture of these products; and added to our intellectual property position. We are positioned to realize the value from these innovative programs. Our excitement about this outcome is being bolstered by the increase in public policy sentiment supporting the need for new prevention and treatment approaches based on innovative applications of vaccine and antibody technologies.”
Partnering to Develop Vaccines Program; Nabi Biopharmaceuticals to Fund Advancing the Antibody Program
Mr. McLain continued, “Based on the conclusions reached in working with the advisory panel, we believe that collaboration with a partner to develop and commercialize our Gram-positive vaccine candidates in larger at-risk populations will maximize the return from this important application of our technology platform. We believe the assessment and review have affirmed the commercial potential for a next-generation StaphVAX product and will enhance interest we have received from pharmaceutical companies in partnering on our vaccine programs.”
Partnering the vaccine programs will build upon the research, development, clinical study and market research experience Nabi Biopharmaceuticals has developed in this specialized area. An ideal partner would contribute additional experience and expertise in vaccine development and commercialization, as well as the financial resources to advance these programs. Further, since 2000, the incidence of S. aureus infections in the community has continued to increase as the bacteria have become more virulent. A partner with the relevant vaccine expertise can support broadening the use of the vaccine to prevent infections in populations such as children, the elderly, athletes and prisoners who are at increasing risk for community- acquired S. aureus infections.
The Altastaph opportunity is particularly relevant to Nabi Biopharmaceuticals’ business strategy. As an antibody product, Altastaph not only represents a significant commercial opportunity, but it also leverages all elements of the value chain within Nabi Biopharmaceuticals. That strong alignment extends from product development, to donor stimulation, antibody collection and manufacturing, and finally through the commercialization of specialized products in the hospital setting.
The conclusions drawn from assessment panel also support the importance of Nabi Biopharmaceuticals’ next-generation Altastaph product. Consistent with the objectives outlined for the company’s Gram-positive program earlier in 2006, Nabi Biopharmaceuticals plans to fund its development through a Phase II proof-of-concept study. This is based on three key considerations:
First, the development of a multi-valent antibody product should be faster than a multi-valent vaccine. The expected timeline advantages acknowledge important differences in terms of manufacturing and clinical studies.
Second, the cost of the development program should be less than for a vaccine development program. The target populations for an antibody product are well-defined. The size of clinical studies is expected to be in the hundreds versus the thousands required for a vaccine efficacy study.
Finally, development of an antibody product should not only provide important proof for a complementary vaccine approach, but it can also enhance the development and testing of vaccine candidates.
It is also important to recognize that the clinical potential for Nabi Biopharmaceuticals’ antibody product in this area was demonstrated previously. The results from a Phase I/II study in adults with active S. aureus infection were announced in January 2005. The Altastaph used in that study had been manufactured with antibodies from a lot of StaphVAX produced in Nabi Biopharmaceuticals’ research and development pilot manufacturing facility.
The company plans to expand the antigens for this product in its proof-of- concept study. The study will be initiated in first half of 2007 for S. aureus Types 5, 8 and 336 and S. epidermidis PS-1. This next-generation product will be developed to demonstrate the treatment and prevention benefits of the antibody formulation in at-risk patients in the hospital setting. The company will work with its advisory panel to define the study population and the design of the trial. In the future there is also the potential to conduct combination studies with the antibody product dosed to treat infections in the hospital and the vaccine dosed at discharge to address the long-term risk for recurrence of infection.
Program Overview and Milestones
In 2006, the company will be able to fund efforts to advance the immediate next steps in developing multi-valent vaccine and antibody products in earlier-stage clinical studies.
These next-generation programs are being designed to study antigens to S. aureus Types 5, 8 and 336 and S. epidermidis Type PS-1. Such an approach will address the strains responsible for essentially 100 percent of healthcare- associated S. aureus infections today, as well as the cause of an estimated 70 percent of healthcare-associated S. epidermidis infections. This is important because broader coverage with optimal antibodies will expand the patient population, increase the effectiveness of those antibodies and also reduce the size and cost of future clinical studies. The company will also advance the ongoing development of other important antigens to address other strains of bacteria and toxins associated with infections, including the Panton Valentine Leukocydin, which can cripple the immune system in patients infected with strains producing this toxin. These next-generation advancements will be important in assuring that there are effective means for preventing and treating Gram-positive infections as these bacteria continue to become more virulent.
Next-generation StaphVAX
Approach: Develop a vaccine that will provide the broadest protection to the most vulnerable patients. Initially advance a vaccine with antigens to S. aureus Types 5, 8 and 336 and S. epidermidis PS-1. Advance and fold in additional antigens to the bacteria and toxins released by the bacteria. To advance the vaccine program’s clinical development, Nabi Biopharmaceuticals will partner with a company that possesses complementary resources and expertise to help fund this program.
Clinical Milestones:
-- 2H 2006: Initiate an immunogenicity study with a multi-valent vaccine, including antigens to S. aureus Types 5, 8 and 336 and S. epidermidis PS-1. Advance early development of additional antigens including S. epidermidis GP-1 and Panton Valentine Leukocydin.
-- 2007: With a partner, initiate a prevention study in a broader array of patients at risk for Gram-positive infections.
Next-generation Altastaph
Approach: Develop an antibody to treat for patients with persistent S. aureus and S. epidermidis infections and those who don’t optimally respond to an antibiotic; a prophylaxis for patients (e.g., ICU patients; emergency surgery patients; and neonates) who are at risk for S. epidermidis and S. aureus infections; and a combination antibody and vaccine regimen designed to prevent recurrence of these infections in hospital patients.
Clinical Milestones:
-- 1H 2006: Initiate a donor stimulation study to support the manufacture of a clinical lot of the next-generation Altastaph antibody product based on S. aureus Types 5, 8, 336 and S. epidermidis PS-1 antigen.
-- 1H 2007: Initiate a proof-of-concept study with next-generation Altastaph, funded by Nabi Biopharmaceuticals.
In advancing these programs, Nabi Biopharmaceuticals will continue to work with its current outside advisory panel, but plans to expand it to include a greater number of relevant experts in the fields of conjugate polysaccharide vaccines and infectious disease.
About the conference call
The live webcast can be accessed at http://audioevent.mshow.com/294370 or via the Nabi Biopharmaceuticals website at http://www.nabi.com . If you do not have Internet access, the U.S./Canada call-in number is 866-467-0407 conference code 6892493, and the international call-in number is 706-679-1697 conference code 6892493. An audio replay will be available for U.S./Canada callers at 800-642-1687 conference code 6892493, and for international callers at 706-645-9291 conference code 6892493.
An archived version of the webcast will be available at the same Internet address through March 28, 2006. The audio replay will also be available through March 28, 2006. The press release will be available on the company’s website at http://www.nabi.com .
About Nabi Biopharmaceuticals
Nabi Biopharmaceuticals leverages its experience and knowledge in powering the immune system to develop and market products that fight serious medical conditions. The company has three products on the market today: PhosLo(R) (calcium acetate), Nabi-HB(R) [Hepatitis B Immune Globulin (Human)], and Aloprim(TM) (allopurinol sodium) for Injection. Nabi Biopharmaceuticals is focused on developing products that address unmet medical needs and offer commercial opportunities in our core business areas: Gram-positive bacterial infections, hepatitis, kidney disease (nephrology) and nicotine addiction. For a complete list of pipeline products, please go to: http://www.nabi.com/pipeline/index.php . The company is headquartered in Boca Raton, Florida. For additional information about Nabi Biopharmaceuticals, please visit our website at: http://www.nabi.com .
Statements in this press release about the company that are not strictly historical are forward-looking statements and include statements about our products in development, the market for such products, clinical trials and studies, intellectual property position, and alliances and partnerships. You can identify these forward-looking statements because they involve our expectations, beliefs, plans, projections, or other characterizations of future events or circumstances. These forward-looking statements are not guarantees of future performance and are subject to risks and uncertainties that may cause actual results to differ materially from those in the forward- looking statements as a result of any number of factors. These factors include, but are not limited to, risks relating to the company’s ability to advance the development of products currently in the pipeline or in clinical trials; maintain the human and financial resources to commercialize current products and bring to market products in development; obtain regulatory approval for its products in the U.S., Europe or other markets; successfully develop, manufacture and market its products; realize future sales growth for its biopharmaceutical products; secure patent positions and prevail in patent litigation; raise additional capital on acceptable terms; and re-pay its outstanding convertible senior notes when due. Many of these factors are more fully discussed, as are other factors, in the company’s Annual Report on Form 10-K for the fiscal year ended December 31, 2005 filed with the Securities and Exchange Commission.
Audio: http://audioevent.mshow.com/294370Nabi Biopharmaceuticals
CONTACT: Thomas E. Rathjen, Vice President, Investor Relations, NabiBiopharmaceuticals, +1-561-989-5800
