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Teva Announces Publication of Phase III Trial Data of Fremanezumab for the Preventive Treatment of Episodic Migraine in the Journal of the American Medical Association

Update: Ajovy (fremanezumab-vfrm) Now FDA Approved - September 14, 2018

JERUSALEM--(BUSINESS WIRE)--May 15, 2018-- Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA) today announced the publication of data from the Phase III HALO study evaluating the efficacy, safety, and tolerability of both quarterly (every three months) and monthly subcutaneous dosing regimens of fremanezumab for the prevention of episodic migraine (EM). These pivotal data were published online today by The Journal of the American Medical Association (JAMA). Fremanezumab is a monoclonal antibody that selectively targets CGRP (calcitonin gene-related peptide), a neuropeptide involved in the pathophysiology of migraine. The study evaluated the use of both quarterly and monthly dosing regimens of subcutaneous fremanezumab, compared with placebo in patients with EM (defined as 14 migraine headache days or less per month) who had previously failed multiple medication classes.

"The results of the HALO study are encouraging and provide insight into the effect of targeting the underlying biological mechanisms of migraine," said Tushar Shah, M.D., Senior Vice President, Head of Specialty Clinical Development at Teva. "Acute migraine treatments were permitted in this study, and a subset of patients were allowed to continue treatment with existing preventive migraine therapies while using fremanezumab. Results from this trial may offer insight into helping patients achieve their treatment goals including those patients who continue to experience disabling migraine."

The HALO EM trial met its primary endpoint demonstrating that fremanezumab significantly reduced monthly migraine days for both quarterly and monthly dosing regimens:

  • The baseline mean number of monthly migraine days was 8.9, 9.2, and 9.1 days in the monthly dosing, quarterly dosing, and placebo groups, respectively. During the 12-week period after the first dose, fremanezumab treatment significantly reduced monthly migraine days to 4.9 days for monthly (P < 0.001) and 5.3 days for quarterly (P < 0.001) dosing compared with 6.5 days for placebo.
    Response rates of ≥50% reduction in monthly average number of migraine days were also significantly greater in monthly (47.7%, P < 0.001) and quarterly (44.4%, P < 0.001) dosing compared with placebo (27.9%).
    Additionally, the baseline mean number of monthly days of any acute headache medication use was 7.7, 7.9, and 7.7 days in the monthly, quarterly, and placebo groups, respectively. Fremanezumab significantly reduced monthly days of any acute headache medication use to 4.4 days for monthly (P < 0.001) and 4.6 days for quarterly (P < 0.001) dosing compared with 5.8 days for placebo.

The mean change in the Migraine Disability Assessment (MIDAS) score was also measured. The MIDAS questionnaire assesses headache-related disability based on lost days of activity over the previous three months, with scores of 0–5 (little or no disability), 6–10 (mild disability), 11–20 (moderate disability), and ≥21 (severe disability). Baseline mean MIDAS scores were 38.0, 41.7, and 37.3 points in the monthly, quarterly, and placebo groups, respectively. MIDAS scores improved with fremanezumab to 12.6 points for monthly (P < 0.001) and 14.6 points for quarterly (P = 0.002) dosing compared with 19.4 points for placebo. The multicenter, randomized, double-blind, placebo-controlled, parallel-group study enrolled 875 patients and consisted of a screening visit, 28-day pre-treatment period, 12-week treatment period, and final evaluation at week 12. The most common adverse events in patients treated with fremanezumab were injection site pain, induration, and erythema.

"With this publication in JAMA, all Phase II and Phase III studies of fremanezumab have now been published in prominent peer-reviewed medical journals which highlights the importance of these data for the migraine community," said Daniel McBryan, M.D., Head of Global Medical Affairs at Teva. "With millions of people suffering from migraine headaches that are often debilitating, these results demonstrate the potential of fremanezumab as another treatment option for patients in need."

About Fremanezumab

Fremanezumab is an investigational therapy currently under review by the U.S. Food and Drug Administration (FDA) as a quarterly or monthly injection for the preventive treatment of migraine in adults.

Fremanezumab is a monoclonal antibody targeting the CGRP (calcitonin gene-related peptide) ligand, currently being investigated as a preventive treatment for migraine. With limited availability of preventive treatment options, fremanezumab represents a potential new option to address a significant unmet medical need.

About the HALO Clinical Research Program

The Phase III HALO EM and CM studies were 16-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group studies to compare the safety, tolerability, and efficacy of four dose regimens of subcutaneous fremanezumab compared to placebo in adults with episodic and chronic migraine. The studies consisted of a screening visit, a 28-day run-in period, and a 12-week (84-day) treatment period, including a final evaluation at week 12 (end-of-treatment [EOT] visit, four weeks [28 days] after the final dose of study drug).

In the EM study, 875 patients were enrolled (294, 291, 290 patients in the placebo, quarterly, and monthly dose groups, respectively). Patients were randomized in a 1:1:1 ratio to receive subcutaneous injections of fremanezumab at 225 mg for three months (monthly dose regimen), fremanezumab at 675 mg at initiation followed by placebo for two months (quarterly dose regimen), or three monthly doses of matching placebo. The primary efficacy endpoint of the EM study was the mean change from baseline (28-day run-in period) in the monthly average number of migraine days during the 12-week period after the first dose of fremanezumab.

In the CM study, 1,130 patients were randomized (around 376 patients per treatment group). Patients were randomized in a 1:1:1 ratio to receive subcutaneous injections of fremanezumab at 675 mg at initiation followed by monthly 225 mg for two months (monthly dose regimen), fremanezumab at 675 mg at initiation followed by placebo for two months (quarterly dose regimen), or three monthly doses of matching placebo. The primary efficacy endpoint of the CM study was the mean change from baseline (28-day run-in period) in the monthly average number of headache days of at least moderate severity during the 12-week period after the first dose of fremanezumab.

About Migraine

Migraine is an unpredictable neurological condition with symptoms such as severe head pain and physical impairment that can impact quality of life and productivity. There are two clinical manifestations of migraine – chronic, where patients suffer 15 or more headache days per month, and episodic, where patients have 14 or less headache days per month. Worldwide, approximately 90% of people diagnosed with migraine have episodic migraine and 10% have chronic migraine.

With more than 1 billion people affected worldwide, migraine is the third most prevalent illness in the world and the 6th most disabling illness in the world. In the U.S., EU5 and Japan, nearly 75 million people suffer from episodic and chronic migraine – more than 38 million in the U.S. alone. Of the approximately 40% of patients suffering from migraine for whom prevention is appropriate, only 13% are currently receiving therapy. There remains a significant medical need for treatments designed specifically to prevent migraine. According to recent analysis, the economic burden for migraine patients reaches approximately $78 billion per year in the U.S.

About Teva

Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA) is a leading global pharmaceutical company that delivers high-quality, patient-centric healthcare solutions used by millions of patients every day. Headquartered in Israel, Teva is the world's largest generic medicines producer, leveraging its portfolio of more than 1,800 molecules to produce a wide range of generic products in nearly every therapeutic area. In specialty medicines, Teva has a world-leading position in innovative treatments for disorders of the central nervous system, including pain, as well as a strong portfolio of respiratory products. Teva integrates its generics and specialty capabilities in its global research and development division to create new ways of addressing unmet patient needs by combining drug development capabilities with devices, services and technologies. Teva's net revenues in 2017 were $22.4 billion. For more information, visit www.tevapharm.com.

Cautionary Note Regarding Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 regarding Fremanezumab, which are based on management's current beliefs and expectations and are subject to substantial risks and uncertainties, both known and unknown, that could cause our future results, performance or achievements to differ significantly from that expressed or implied by such forward-looking statements. Important factors that could cause or contribute to such differences include risks relating to: challenges inherent in product research and development, including uncertainty of clinical success and obtaining regulatory approvals; our ability to successfully compete in the marketplace, including: that we are substantially dependent on our generic products; competition for our specialty products, especially COPAXONE®, our leading medicine, which faces competition from existing and potential additional generic versions and orally-administered alternatives; competition from companies with greater resources and capabilities; efforts of pharmaceutical companies to limit the use of generics including through legislation and regulations; consolidation of our customer base and commercial alliances among our customers; the increase in the number of competitors targeting generic opportunities and seeking U.S. market exclusivity for generic versions of significant products; price erosion relating to our products, both from competing products and increased regulation; delays in launches of new products and our ability to achieve expected results from investments in our product pipeline; our ability to take advantage of high-value opportunities; the difficulty and expense of obtaining licenses to proprietary technologies; and the effectiveness of our patents and other measures to protect our intellectual property rights; our substantially increased indebtedness and significantly decreased cash on hand, which may limit our ability to incur additional indebtedness, engage in additional transactions or make new investments, and may result in a further downgrade of our credit ratings; and our inability to raise debt or borrow funds in amounts or on terms that are favorable to us; our business and operations in general, including: failure to effectively execute the restructuring plan announced in December 2017; uncertainties related to, and failure to achieve, the potential benefits and success of our new senior management team and organizational structure; harm to our pipeline of future products due to the ongoing review of our R&D programs; our ability to develop and commercialize additional pharmaceutical products; potential additional adverse consequences following our resolution with the U.S. government of our FCPA investigation; compliance with sanctions and other trade control laws; manufacturing or quality control problems, which may damage our reputation for quality production and require costly remediation; interruptions in our supply chain; disruptions of our or third party information technology systems or breaches of our data security; the failure to recruit or retain key personnel; variations in intellectual property laws that may adversely affect our ability to manufacture our products; challenges associated with conducting business globally, including adverse effects of political or economic instability, major hostilities or terrorism; significant sales to a limited number of customers in our U.S. market; our ability to successfully bid for suitable acquisition targets or licensing opportunities, or to consummate and integrate acquisitions; and our prospects and opportunities for growth if we sell assets; compliance, regulatory and litigation matters, including: costs and delays resulting from the extensive governmental regulation to which we are subject; the effects of reforms in healthcare regulation and reductions in pharmaceutical pricing, reimbursement and coverage; governmental investigations into sales and marketing practices; potential liability for patent infringement; product liability claims; increased government scrutiny of our patent settlement agreements; failure to comply with complex Medicare and Medicaid reporting and payment obligations; and environmental risks; other financial and economic risks, including: our exposure to currency fluctuations and restrictions as well as credit risks; potential impairments of our intangible assets; potential significant increases in tax liabilities; and the effect on our overall effective tax rate of the termination or expiration of governmental programs or tax benefits, or of a change in our business; and other factors discussed in our Annual Report on Form 10-K for the year ended December 31, 2017, including in the section captioned "Risk Factors," and in our other filings with the U.S. Securities and Exchange Commission, which are available at www.sec.gov and www.tevapharm.com. Forward-looking statements speak only as of the date on which they are made, and we assume no obligation to update or revise any forward-looking statements or other information contained herein, whether as a result of new information, future events or otherwise. You are cautioned not to put undue reliance on these forward-looking statements.

Source: Teva Pharmaceutical Industries Ltd.

Posted: May 2018

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