New Data Presented at 29th ECTRIMS Congress Reinforce the Clinical Profile of Investigational Laquinimod on Disease Progression and Inflammation in Relapsing-Remitting Multiple SclerosisOctober 4, 2013 15:30 (CEST)
Pooled Data Analysis of Phase III ALLEGRO and BRAVO Studies Add to our Understanding of Investigational Laquinimod for Relapsing-Remitting Multiple Sclerosis (RRMS)
Jerusalem & Lund, Sweden, October 4, 2013 - Teva Pharmaceutical Industries Ltd. (NYSE: TEVA) and Active Biotech (NASDAQ OMX NORDIC: ACTI) announced today the presentation of post-hoc analyses of the Phase III ALLEGRO and BRAVO studies supporting that once-daily, oral laquinimod may have an effect on both inflammation and the broader underlying mechanisms associated with disease progression in relapsing-remitting multiple sclerosis. Various new laquinimod data will be featured in 16 scientific posters and presentations at the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in Copenhagen, Denmark, October 2-5, 2013.
"Several post-hoc analyses of the pooled data from the ALLEGRO and BRAVO Phase III studies demonstrates that the trend of efficacy results was maintained in the analysis of data pooled from the two studies, and is consistent with the proposed mechanism of action for laquinimod, " said Dr. Michael Hayden, President of Global R&D and Chief Scientific Officer for Teva Pharmaceutical Industries Ltd. "Teva remains committed to the laquinimod clinical development program in MS and in other diseases characterized by a neurodegenerative pathology, and to addressing the needs of these patients worldwide."
Results from a post-hoc subgroup analysis of pooled data from the Phase III double-blind ALLEGRO and BRAVO studies showed there were some patients who experienced disease progression without experiencing a relapse during the studies. Regardless of treatment arm and despite relapse status, 12 percent of patients studied experienced disability progression after two years; of those patients who progressed, approximately one-third did not experience a relapse. Results specific to treatment with laquinimod showed that both relapsing and relapse-free patients treated with laquinimod experienced less disease progression than those treated with placebo. Overall, laquinimod reduced three-month confirmed disability progression by 26.7 percent in relapsing patients (P=0.058) and 38.9 percent in relapse-free patients (P=0.036) compared to placebo.
"We have made significant progress in understanding the pathology of multiple sclerosis however it remains a complex and often unpredictable disease," said Professor Giancarlo Comi, Director of the Department of Neurology and Institute of Experimental Neurology at the San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Italy. "When patients show disease progression but do not experience a relapse, it suggests that disability progression and relapses are not solely mediated through a common pathway. The data presented at ECTRIMS support the notion that laquinimod may have an effect not only on acute inflammatory attacks but also on broader underlying mechanisms."
Results of this and additional post-hoc analyses of the pooled data from the ALLEGRO and BRAVO Phase III studies reinforcing the novel clinical profile of laquinimod on disease progression and inflammation will be presented at the ECTRIMS Congress as follows:
· Disease progression in relapse-free patients treated with laquinimod, Friday, October 4, 15:30 - 17:00 CET (P1036, Poster Session: Long-term treatment monitoring)
· Bayesian analysis of laquinimod's effect on relapses and disability, Thursday, October 3, 14:30 - 17:00 CET (P606, Poster Session: Tools for detecting therapeutic response)
· Evaluating the relationship between laquinimod's effects on relapse and disability progression, Friday, October 4, 15:30 - 17:00 CET (P1080, Poster Session: Tools for detecting therapeutic response)
· The risk of disability progression is associated with multiple sclerosis functional composite (MSFC) scores in the laquinimod phase 3 trials, Friday, October 4, 15:30 - 17:00 CET (P1057, Poster Session: Long-term treatment monitoring)
Both the ALLEGRO and BRAVO studies found that laquinimod demonstrated a tolerable clinical profile compared to placebo. The overall frequencies of adverse events, including incidence of infections, were comparable to those observed in the placebo group. The most commonly reported adverse events were headaches, nasopharyngitis and back pain. The incidence of liver enzyme elevation was higher in laquinimod treated patients; however, these elevations were transient, asymptomatic and reversible.
ABOUT THE ALLEGRO STUDY
ALLEGRO was a two-year, multi-national, multi-center randomized, double blind, placebo-controlled study designed to evaluate the efficacy, safety and tolerability of laquinimod in MS patients. The study was conducted at 139 sites in 24 countries and enrolled 1,106 MS patients. Patients were randomized to receive a once-daily oral dose of 0.6 mg laquinimod or matching placebo. The primary outcome measure was the number of confirmed relapses; secondary measures included confirmed disability progression and changes in MRI active lesions.
In the ALLEGRO study, laquinimod showed a statistically significant 23 percent reduction in annualized relapse rate (p=0.0024), the primary endpoint, along with a significant 36 percent reduction in the risk of confirmed disability progression, as measured by Expanded Disability Status Scale (EDSS) (p=0.0122). Treatment with laquinimod was also associated with a significant reduction in brain tissue loss, as measured by a 33 percent reduction in progression of brain atrophy (p<0.0001).
Eighty percent of laquinimod and 77 percent of placebo patients completed the two-year study. Patients who completed the ALLEGRO study were offered to join an open-label extension phase, in which they are being treated with laquinimod 0.6 mg daily.
ABOUT THE BRAVO STUDY
BRAVO was a two-year, multi-national, multi-center, randomized, double-blind, parallel-group, placebo-controlled study designed to compare the safety, efficacy and tolerability of a once-daily oral dose of 0.6 mg laquinimod over placebo and to provide a descriptive comparison of the risk-benefit profiles of laquinimod and interferon beta-1a. The primary outcome measure was to assess the efficacy of 0.6 mg daily dose of laquinimod as measured by the relapse rate. Secondary outcome measures included impact on the accumulation of disability and brain atrophy. The BRAVO study completed enrollment in June 2009, recruiting more 1,331 patients at 153 sites worldwide, including in the U.S., Europe, Russia, Israel and South Africa.
Results showed that the BRAVO study did not achieve its primary endpoint of reducing the annualized relapse rate (p=0.075).
Laquinimod is an oral, investigational, CNS-active immunomodulator with a novel mechanism of action being developed for the treatment of relapsing-remitting MS (RRMS). The global Phase III clinical development program evaluating oral laquinimod in MS includes two pivotal studies, ALLEGRO and BRAVO. A third Phase III laquinimod trial, CONCERTO, is evaluating two doses of the investigational product (0.6mg and 1.2mg) in approximately 1,800 patients for up to 24 months. The primary outcome measure will be time to confirmed disability progression as measured by the EDSS.
In addition to the MS clinical studies, laquinimod is currently in Phase II of development for Crohn's disease and lupus nephritis. Further studies are planned to determine the effectiveness of laquinimod in treating patients with Huntington's disease and Alzheimer's disease.
Teva Pharmaceutical Industries Ltd. (NYSE: TEVA) is a leading global pharmaceutical company, committed to increasing access to high-quality healthcare by developing, producing and marketing affordable generic drugs as well as innovative and specialty pharmaceuticals and active pharmaceutical ingredients. Headquartered in Israel, Teva is the world's leading generic drug maker, with a global product portfolio of more than 1,000 molecules and a direct presence in about 60 countries. Teva's branded businesses focus on CNS, oncology, pain, respiratory and women's health therapeutic areas as well as biologics. Teva currently employs approximately 46,000 people around the world and reached $20.3 billion in net revenues in 2012.
ABOUT ACTIVE BIOTECH
Active Biotech AB (NASDAQ OMX NORDIC: ACTI) is a biotechnology company with focus on autoimmune/inflammatory diseases and cancer. Projects in or entering pivotal phase are laquinimod, an orally administered small molecule with unique immunomodulatory properties for the treatment of multiple sclerosis, TASQ for prostate cancer as well as ANYARA for use in cancer targeted therapy, primarily of renal cell cancer. In addition, laquinimod is in Phase II development for Crohn's and Lupus. Further projects in clinical development comprise the two orally administered compounds, 57-57 for SLE & Systemic Sclerosis and RhuDex(TM) for RA. Please visit http://www.activebiotech.com for more information.
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This release contains forward-looking statements, which express the current beliefs and expectations of management. Such statements are based on management's current beliefs and expectations and involve a number of known and unknown risks and uncertainties that could cause our future results, performance or achievements to differ significantly from the results, performance or achievements expressed or implied by such forward-looking statements. Important factors that could cause or contribute to such differences include risks relating to: our ability to develop and commercialize additional pharmaceutical products, competition for our innovative products, especially Copaxone® (including competition from innovative orally-administered alternatives, as well as from potential purported generic equivalents), competition for our generic products (including from other pharmaceutical companies and as a result of increased governmental pricing pressures), competition for our specialty pharmaceutical businesses, our ability to achieve expected results through our innovative R&D efforts, the effectiveness of our patents and other protections for innovative products, decreasing opportunities to obtain U.S. market exclusivity for significant new generic products, our ability to identify, consummate and successfully integrate acquisitions, the effects of increased leverage as a result of recent acquisitions, the extent to which any manufacturing or quality control problems damage our reputation for high quality production and require costly remediation, our potential exposure to product liability claims to the extent not covered by insurance, increased government scrutiny in both the U.S. and Europe of our agreements with brand companies, potential liability for sales of generic products prior to a final resolution of outstanding patent litigation, our exposure to currency fluctuations and restrictions as well as credit risks, the effects of reforms in healthcare regulation and pharmaceutical pricing and reimbursement, any failures to comply with complex Medicare and Medicaid reporting and payment obligations, governmental investigations into sales and marketing practices (particularly for our specialty pharmaceutical products), uncertainties surrounding the legislative and regulatory pathways for the registration and approval of biotechnology-based products, adverse effects of political or economical instability, corruption, major hostilities or acts of terrorism on our significant worldwide operations, interruptions in our supply chain or problems with our information technology systems that adversely affect our complex manufacturing processes, any failure to retain key personnel or to attract additional executive and managerial talent, the impact of continuing consolidation of our distributors and customers, variations in patent laws that may adversely affect our ability to manufacture our products in the most efficient manner, potentially significant impairments of intangible assets and goodwill, potential increases in tax liabilities, the termination or expiration of governmental programs or tax benefits, environmental risks and other factors that are discussed in our Annual Report on Form 20-F for the year ended December 31, 2012 and in our other filings with the U.S. Securities and Exchange Commission. Forward-looking statements speak only as of the date on which they are made and the Company undertakes no obligation to update or revise any forward-looking statement, whether as a result of new information, future events or otherwise.
Active Biotech's Safe Harbor Statement in Accordance with the Swedish Securities Market Act:
This press release contains certain forward-looking statements. Such forward-looking statements involve known and unknown risks, uncertainties and other important factors that could cause the actual results, performance or achievements of the company, or industry results, to differ materially from any future results, performance or achievement implied by the forward-looking statements. The company does not undertake any obligation to update or publicly release any revisions to forward-looking statements to reflect events, circumstances or changes in expectations after the date of this press release.
Active Biotech is obligated to publish the information contained in this press release in accordance with the Swedish Securities Market Act. This information was provided to the media for publication 3:30 pm CET on October 4, 2013.
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