Bioverativ’s Investigational BIVV009 Demonstrates Safety, Tolerability and Efficacy in Phase 1b Clinical Trial in Cold Agglutinin Disease (CAgD) Patients

ATLANTA--(BUSINESS WIRE)-- Bioverativ (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 59^th 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 Risk
A 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 BIVV009
BIVV009 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 Bioverativ
Bioverativ (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 Harbor
This 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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