Lev Presents Results of Phase III Study Supporting Safety and Efficacy of Cinryze (C1 inhibitor) as Prophylactic Therapy for HAE
The multi-center study observed the effect of Cinryze on the frequency of HAE attacks, which are characterized by disfiguring and painful swelling of the extremities, face, abdomen, urogenital tract and - most dangerously - laryngeal tract. In the 24 week, double-blind, placebo controlled study, 22 patients who met the diagnostic criteria for HAE and who had a history of at least two attacks per month were randomized to receive 12 weeks of either Cinryze or a placebo. After 12 weeks, the study arms were switched so that the patients on the placebo arm were given Cinryze for 12 weeks and vice versa. All patients were eligible to receive open label Cinryze for acute attacks.
The primary endpoint was met with a 52% reduction in the number of attacks in the Cinryze(TM) group (p<0.0001). Secondary endpoints in the study also showed highly significant differences in favor of Cinryze, including a 66% reduction in days of swelling (p<0.0001) and decreases in the average severity of attacks (p=0.0008) and average duration of attacks (p=0.0004). No safety issues were identified.
"Patients with hereditary angioedema live with the constant threat of severe and potentially life-threatening angioedema attacks," said Bruce Zuraw, MD, Program Director of the Allergy and Immunology Fellowship Program at the University of California at San Diego and the study's primary investigator. "Current therapeutic options for preventing these attacks are not universally effective and are frequently accompanied by undesirable side effects. The results of this study provide evidence that C1 inhibitor replacement therapy is an effective new approach for preventing angioedema attacks. This could represent an important advance in hereditary angioedema treatment in the United States."
The current means of preventing HAE attacks - treatment with anabolic steroids - is not disease specific and does not affect the pathophysiology of HAE - C1 inhibitor deficiency. Anabolic steroids also carry the risk of significant adverse effects, such as liver toxicity and virilization, and are not a realistic option for a large segment of the population, including women and children.
Additionally, Cinryze(TM) was well tolerated with an adverse event profile no different from placebo. The most common adverse reactions observed were injection site rash and lightheadedness. No drug-related serious adverse events (SAEs), no immunogenicity and no decrease in efficacy have been observed.
"We are pleased that this study corroborates the years of clinical evidence supporting the prophylactic use of C1 inhibitor replacement therapy in European patients with hereditary angioedema, said Joshua Schein, chief executive officer of Lev. "With this validation, we hope to secure FDA approval so we can begin providing this life-saving therapy to the thousands of U.S. patients who need it."
Lev's Cinryze is the only product currently being developed for prophylactic treatment of HAE.
Another abstract presented at the AAAAI meeting focused on the mechanism of bradykinin generation in HAE. In that presentation, Allen Kaplan, MD, Professor of Medicine at the Medical University of South Carolina, demonstrated that therapy with purified C1 inhibitor should prevent bradykinin formation, increased fibrinolytic activity, and activation of the classical complement pathway. Lev believes that these findings further support the use of Cinryze as replacement therapy for HAE.
About Hereditary Angioedema
HAE is a rare, severely debilitating, life-threatening genetic disorder caused by a deficiency of C1 inhibitor, a human plasma protein. This condition is the result of a defect in the gene controlling the synthesis of C1 inhibitor. C1 inhibitor maintains the natural regulation of the contact, complement, and fibrinolytic systems, that when left unrestricted, can initiate or perpetuate an attack by consuming the already low levels of endogenous C1 inhibitor in HAE patients. Patients with C1 inhibitor deficiency experience recurrent, unpredictable, debilitating, and potentially life threatening attacks of inflammation affecting the larynx, abdomen, face, extremities and urogenital tract.
There are estimated to be 10,000 people with HAE in the United States and currently, there are no approved therapies for acute HAE attacks in the U.S.
For more information on HAE, visit the U.S. HAE Association's website at: www.haea.org.
Cinryze is a C1 inhibitor replacement therapy that treats the underlying cause of hereditary angioedema (HAE) - a deficiency of the C1 inhibitor plasma protein that mediates swelling. Cinryze offers both acute and prophylactic treatment of HAE attacks.
C1 inhibitor replacement therapy has been used to safely and effectively treat and prevent HAE attacks in Europe for 35 years.
An advisory committee to the U.S. Food and Drug Administration will meet on May 2, 2008 to review Lev's Biologics License Application (BLA) for Cinryze.
About Lev Pharmaceuticals, Inc.
Lev is a biopharmaceutical company focused on developing and commercializing therapeutic products for the treatment of inflammatory diseases. Lev's lead product candidate, Cinryze (C1 inhibitor), is being developed as a replacement therapy for both the acute and prophylactic treatment of hereditary angioedema (HAE), also known as C1 inhibitor deficiency. Cinryze has been granted orphan drug status for the acute and prophylactic treatment of HAE, potentially securing, upon approval, market exclusivity for seven years. Additionally, Lev is in the process of prioritizing its C1 inhibitor development platform for the treatment of selective other diseases and disorders in which inflammation is known or believed to play an underlying role.
For more information about Lev, C1 inhibitor, or HAE, please contact Lev directly at 212-682-3096, or visit Lev's website at www.levpharma.com.
Forward Looking Statements
This press release contains forward-looking statements that involve substantial risks and uncertainties. All statements, other than statements of historical facts, included in this press release regarding our plans and objectives of management are forward-looking statements. We may not actually achieve the plans, intentions or expectations disclosed in our forward-looking statements and you should not place undue reliance on our forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements we make. Various important factors could cause actual results or events to differ materially from the forward-looking statements that we make, including risks related to new information arising out of clinical trial results, the risk that the safety and/or efficacy results of existing clinical trials for Cinryze will not support approval for a biologics license, the risk that the FDA may require us to conduct additional clinical trials for Cinryze the risk that the FDA may interpret data differently than we do or require more data or a more rigorous analysis of data than expected, the risk that the FDA will not approve a product for which a biologics license has been applied, our heavy dependence on the success of Cinryze, our dependence on our suppliers, our dependence on third parties to manufacture Cinryze, obtaining regulatory approval to market Cinryze, market acceptance of Cinryze, maintaining the orphan drug status associated with Cinryze, the risks associated with dependence upon key personnel, and our ability to obtain additional funding to support our business activities. These and other risks are described in greater detail in the "Risk Factors that May Affect Results" section of our filings with the SEC. Our forward-looking statements do not reflect the potential impact of any future acquisitions, mergers, dispositions, joint ventures or investments we may make. We do not assume any obligation to update any forward-looking statements.
Posted: March 2008