-- Development of StaphVAX and Altastaph to Continue --
-- Company to Hold Conference Call on March 21 at 5:00 PM, Eastern Time --
BOCA RATON, Fla., March 21 /PRNewswire-FirstCall/ -- Nabi
Biopharmaceuticals (Nasdaq: NABI) 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.
SOURCE Nabi Biopharmaceuticals
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Related links:
http://www.nabi.com
http://www.nabi.com/pipeline/index.php
Audio:http://audioevent.mshow.com/294370
CONTACT:
Thomas E. Rathjen, Vice President, Investor
Relations, Nabi Biopharmaceuticals, +1-561-989-5800
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