- Phase 1b results achieve primary and
secondary endpoints in CAgD cohort
- Six of six primary CAgD patients had an
increase in hemoglobin of 4 g/dl or more, and remained
transfusion-free during treatment
- Largest CAgD natural history study to date
quantifies increased risk of thromboembolic events
Bioverativ Inc. (NASDAQ: BIVV), a global biopharmaceutical
company dedicated to transforming the lives of people with rare
blood disorders, today presented data demonstrating that BIVV009,
its first-in-class monoclonal antibody currently in Phase 3
clinical development for the treatment of cold agglutinin disease
(CAgD), was generally well tolerated, rapidly halted hemolysis, and
improved anemia in six of six severely anemic primary CAgD patients
in a Phase 1b clinical trial. The data were shared in an oral
presentation at the 59th Annual Meeting of the American Hematology
Society.
CAgD is a rare blood disease that results in the premature
destruction of red blood cells (hemolytic anemia) by the body’s
immune system. There are currently no approved treatments for the
disease. BIVV009 has been designed to block the classical
complement pathway – a key pathway that triggers the immune system
to remove damaged cells. It is believed that this approach may
limit the immune system from mistakenly removing red blood cells
and potentially interrupt the CAgD disease process. BIVV009 was
awarded Breakthrough Therapy Designation by the U.S. Food and Drug
Administration based on earlier data from the Phase 1b study.
Primary and secondary outcome measures were achieved in the six
patients with primary CAgD in the study. Hemoglobin levels
increased in all six patients (median >4g/dl), eliminating the
need for transfusions while on treatment. Endpoints included
tolerability, pharmacokinetic profile supporting biweekly dosing,
classical complement pathway inhibition as evidenced by decreased
total complement activity, and improved biomarkers associated with
rapid hemolysis resolution and corresponding improvement in
hemoglobin levels.
Hemolysis and anemia recurred upon clearance of BIVV009 from
circulation (3-4 weeks following the final dose), and efficacy was
restored in all patients upon re-exposure to BIVV009 during a
subsequent Named Patient Program. Maintenance therapy has
demonstrated a sustained response for more than 18 months,
including control of hemolysis. Safety data through December 21,
2016 demonstrated that BIVV009 was generally well tolerated. Five
of 6 patients (83.3%) in the primary CAgD group experienced at
least one adverse event (AE); no AE was reported by more than one
patient. One unrelated, serious AE occurred in a patient with CAgD
who was hospitalized for a pre-existing condition. There were no
serious AEs assessed as related to BIVV009 by the investigator.
“These Phase 1 results reinforce our confidence in the potential
for BIVV009 to make a real difference in the lives of CAgD
patients, who today have no approved treatments to manage their
disease,” said Joachim Fruebis, Senior Vice President of
Development, Bioverativ. “These data show that BIVV009 has the
potential to address patients’ anemia as well as the underlying
hemolysis, which, based on early data may contribute to the
increased thromboembolic risk observed in CAgD patients.”
Natural History Study Reveals Increased Thromboembolic Event
RiskA separate poster presentation provided the results of the
largest retrospective study of CAgD natural history to date,
evaluating clinical characteristics and the occurrence rate of
thromboembolic (TE) events, such as stroke. A review of
de-identified patient information related to claims, medications,
laboratory results, procedures and clinical results over a 10-year
period in the United States identified 814 CAgD patients, which
were compared with a 7,960-member cohort matched for age, gender,
race, region and other measures.
The analysis found a statistically significant 55% overall
increased rate of thromboembolic events in CAgD patients vs.
matched controls (31% vs. 20%), as well as a statistically
significant higher frequency of multiple thromboembolic events. The
risk of thromboembolic events correlated with biomarkers of
hemolysis, bilirubin and lactate dehydrogenase (LDH) levels, but
not with anemia severity.
The review also showed that hemolysis was not resolved in 90% of
patients receiving treatment with rituximab, as demonstrated by
persistently elevated levels of bilirubin and LDH within 12 months
of the last dose. Rituximab is an unapproved but commonly used
treatment option for CAgD, and the only therapy included in the
analysis.
The natural history study also showed:
- Nearly 10% of all CAgD patients had
venous TE events vs. 3% of matched comparisons
- 25% of all CAgD patients had cerebral
TE events vs. 16% of matched comparisons
- 8% of CAgD patients had arterial TE
events vs. 5% of matched comparisons
- All TE event measurements were
statistically significant when compared to matched comparisons
“For the first time, we have been able to quantify the true
frequency of thromboembolic events for CAgD patients, a
complication that, until now, has been underappreciated due to the
rarity of the disease,” said Catherine Broome, M.D., Associate
Professor, Georgetown University. “The data in this study also
provide much needed clarity that markers of hemolysis, and not
severity of anemia, predict an increased risk of these
life-threatening events. This can help us better manage patients
and highlights the need for new treatments that can rapidly control
hemolysis in CAgD patients.”
About BIVV009BIVV009 is a first-in-class, humanized,
monoclonal antibody that is designed to target C1s, a serine
protease within the C1-complex in the complement pathway of the
immune system, and directly impact the central mechanism of CAgD.
With a unique mechanism of action and high target specificity,
BIVV009 is designed to selectively inhibit disease processes in the
classical complement pathway while maintaining activity of the
alternative and lectin complement pathways, which are important for
immune surveillance and other functions.
About Cold Agglutinin Disease (CAgD)CAgD is a
debilitating autoimmune hemolytic anemia in which autoantibodies
target red blood cells, leading to red blood cell destruction via
complement activation initiated by the C1 complex, causing chronic
anemia, severe fatigue, and potentially fatal thrombotic events.
There are no approved therapies for CAgD, which occurs in
approximately 16 people per million, affecting an estimated 10,000
people in the United States and Europe. Symptom onset typically
begins around age 60, and treatment is aimed at normalizing
hemoglobin levels through blood transfusions, steroids, or
off-label immunotoxic therapy. However, current treatment options
are often intensive, incomplete, or nondurable, leaving patients
dependent upon frequent transfusions, which can lead to chronic
iron overload.
About BioverativBioverativ (NASDAQ:BIVV) is a global
biotechnology company dedicated to transforming the lives of people
with hemophilia and other rare blood disorders through world-class
research, development and commercialization of innovative
therapies. Launched in 2017 following separation from Biogen Inc.,
Bioverativ builds upon a strong heritage of scientific innovation
and is committed to actively working with the blood disorders
community. The company’s mission is to create progress for patients
where they need it most and its hemophilia therapies when launched
represented the first major advancements in hemophilia treatment in
more than two decades. For more information, visit
www.bioverativ.com or follow @bioverativ on Twitter.
Bioverativ Safe HarborThis press release contains
forward-looking statements, including statements about the
potential benefits, safety and clinical effects of BIVV009. These
forward-looking statements may be accompanied by such words as
“anticipate,” “believe,” “could,” “estimate,” “expect,” “forecast,”
“intend,” “may,” “plan,” “potential,” “project,” “target,” “will”
and other words and terms of similar meaning. You should not place
undue reliance on these statements. Drug development and
commercialization involve a high degree of risk, and only a small
number of research and development programs result in
commercialization of a product. Results in early stage clinical
trials may not be indicative of full results or results from later
stage or larger scale clinical trials and do not ensure regulatory
approval. Factors which could cause actual results to differ
materially from Bioverativ's current expectations include:
uncertainties relating to the initiation, enrollment and completion
of stages of clinical trials; reliance on third parties for aspects
of clinical trials; unexpected concerns may arise from data,
analysis or results obtained during clinical trials or post hoc
analysis of studies; regulatory authorities may require additional
information or further studies, or may fail or refuse to approve or
may delay approval of product candidates; or Bioverativ may
encounter other unexpected hurdles; and other risks and
uncertainties associated with Bioverativ’s drug development and
commercialization activities described in the Risk Factors section
of Bioverativ’s filings with the Securities and Exchange
Commission. These statements are based on Bioverativ’s current
beliefs and expectations and speak only as of the date of this
press release. Bioverativ does not undertake any obligation to
publicly update any forward-looking statements.
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Bioverativ Inc.Media Contact:Tracy Vineis, +1
781-663-4376media@bioverativ.comorInvestor Relations Contact:Samuel
Chase, +1 781-663-4360IR@bioverativ.com
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