Teva Announces New Analysis of Consistency in Migraine Days Over the Course of a Dosing Regimen for AJOVY® (fremanezumab-vfrm) Injection Published in Headache

Rhea-AI Summary

Teva Pharmaceutical Industries Ltd. announced results from a post hoc analysis of a long-term study on AJOVY® (fremanezumab-vfrm) for chronic and episodic migraine treatment. The analysis involved 1,043 patients, comparing migraine days during different dosing regimens. Findings showed no significant variation in migraine days between initial and final weeks of dosing. The mean weekly migraine days were 4.0 for chronic migraine and 2.3 for episodic migraine at baseline. No new safety signals were identified, and AJOVY remains the only long-acting anti-CGRP injection approved for both quarterly and monthly dosing.

Positive

• The analysis includes 1,043 patients, reinforcing the robustness of the AJOVY data.
• No new safety signals were identified, indicating the treatment's reliability.
• AJOVY is the first long-acting anti-CGRP injection with flexible dosing options.

Negative

• The study's post hoc nature limits definitive conclusions from the results.
• No significant reduction in migraine days between dosing periods raises concerns about efficacy over time.

TEL AVIV, Israel--(BUSINESS WIRE)--Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA) today announced results from a post hoc analysis of a long-term, open-label extension study assessing migraine days at the beginning and end of quarterly and monthly dosing intervals of AJOVY^® (fremanezumab-vfrm) injection. The results were published in the October issue of Headache: The Journal of Head and Face Pain.

“We are proud to share this analysis and demonstrate our continued commitment to advancing the understanding of treatment options for patients living with migraine,” said Denisa Hurtukova, MD, Vice President, Head of North America Medical Affairs, Teva. “This analysis helps us better understand patients’ experience with AJOVY, as well as the impact of quarterly and monthly dosing options.”

The post hoc analysis compared migraine days in the initial and final weeks of quarterly or monthly dosing regimens of AJOVY during up to 15 months of treatment. The analysis included 1,043 patients with chronic migraine (CM) (n=611) and episodic migraine (EM) (n=432) who were initially enrolled in the pivotal placebo controlled HALO CM and EM studies and then continued in the long-term, 12-month, multicenter, randomized, parallel group Phase 3 study with double blind dosing regimens. Patients received AJOVY either quarterly or monthly.

“Utilizing patients within each dosing group as their own control, we were able to analyze whether there was variability in migraine days over the course of a dosing regimen. For all time intervals analyzed, the frequency of migraine days was the same in the beginning and end of the dosing period,” said Joshua M. Cohen, MD, MPH, FAHS, Global Medical Therapeutic Area Lead for Migraine & Headache, Teva.

“This is an important analysis for the migraine community since clinical symptoms often return or worsen before the next dose of many preventive migraine medications is due,” said Andrew Blumenfeld, MD, Headache Center of Southern California, The Neurology Center, Carlsbad, CA. “Migraine can be a debilitating disease, so evaluating migraine days throughout a dosing regimen can be significant for healthcare providers when considering treatment options. Whenever the brain is exposed to a migraine attack, there is the possibility of increased sensitization with progressive worsening of the frequency of migraine. A key clinical goal is to limit the amount of time the brain is exposed to migraine to reduce this risk and the number of migraine days impacting a patient before their next dose.”

The mean weekly number of migraine days at baseline was 4.0 for patients with CM taking quarterly or monthly AJOVY. For patients with EM, the mean weekly number of migraine days at baseline in the quarterly and monthly AJOVY groups were both 2.3 days.

The analysis found:

Mean number of weekly migraine days in weeks 1-2 versus weeks 11-12 with quarterly dosing1*
	First Quarter		Second Quarter
	Weeks 1-2	Weeks 11-12	Weeks 1-2	Weeks 11-12
CM	2.8	2.7	2.5	2.5
EM	1.5	1.3	1.2	1.1
CM: n=348 first quarter, n=283 second quarter; EM: n=262 first quarter, n=195 second quarter

Mean number of weekly migraine days during weeks 1-3 versus week 4 at months 3, 6, 9 and 15 with monthly dosing1*
	Month 3		Month 6		Month 9		Month 15
	Weeks 1-3	Week 4	Weeks 1-3	Week 4	Weeks 1-3	Week 4	Weeks 1-3	Week 4
CM	2.6	2.6	2.3	2.4	2.1	2.1	2.0	1.8
EM	1.2	1.2	1.0	1.0	1.0	1.0	0.8	1.0
CM: n=334 month 3, n=264 month 6, n=250 month 9, n=223 month 15; EM: n=251 month 3, n=191 month 6, n=180 month 9, n=155 month 15

For all post hoc analyses, no determination of statistical significance can be made, and no conclusions should be drawn. No new safety signals were identified in this population that were inconsistent with the known safety profile of AJOVY.

AJOVY is the first and only long-acting anti-CGRP subcutaneous injection approved in the US and EU for the preventive treatment of migraine in adults that offers both quarterly and monthly dosing options.^2+±

U.S. Important Safety Information about AJOVY^® (fremanezumab-vfrm) injection

Contraindications: AJOVY is contraindicated in patients with serious hypersensitivity to fremanezumab-vfrm or to any of the excipients.

Hypersensitivity Reactions: Hypersensitivity reactions, including rash, pruritus, drug hypersensitivity, and urticaria were reported with AJOVY in clinical trials. Most reactions were mild to moderate, but some led to discontinuation or required corticosteroid treatment. Most reactions were reported from within hours to one month after administration. If a hypersensitivity reaction occurs, consider discontinuing AJOVY and institute appropriate therapy.

Adverse Reactions: The most common adverse reactions (≥5% and greater than placebo) were injection site reactions.

Please click here for full U.S. Prescribing Information for AJOVY^® (fremanezumab-vfrm) injection.

Information for Europe about AJOVY^® can be found here.

Adverse events should be reported.

This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse events.

Reporting forms and information can be found at https://www.hpra.ie. Adverse events should also be reported to Teva – please refer to local numbers.

About Teva

Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA) has been developing and producing medicines to improve people’s lives for more than a century. We are a global leader in generic and specialty medicines with a portfolio consisting of over 3,500 products in nearly every therapeutic area. Around 200 million people around the world take a Teva medicine every day, and are served by one of the largest and most complex supply chains in the pharmaceutical industry. Along with our established presence in generics, we have significant innovative research and operations supporting our growing portfolio of specialty and biopharmaceutical products. Learn more at 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 AJOVY^®, 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:

• The commercial success of AJOVY;
• our ability to successfully compete in the marketplace, including: that we are substantially dependent on our generic products; 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; competition for our specialty products, especially COPAXONE^®, our leading medicine, which faces competition from existing and potential additional generic versions, competing glatiramer acetate products and orally-administered alternatives; the uncertainty of commercial success of AJOVY or AUSTEDO^®; competition from companies with greater resources and capabilities; delays in launches of new products and our ability to achieve expected results from investments in our product pipeline; ability to develop and commercialize biopharmaceutical products; efforts of pharmaceutical companies to limit the use of generics, including through legislation and regulations and the effectiveness of our patents and other measures to protect our intellectual property rights;
• our substantial indebtedness, which may limit our ability to incur additional indebtedness, engage in additional transactions or make new investments, 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: uncertainty regarding the magnitude, duration, and geographic reach of the COVID-19 pandemic and its impact on our business, financial condition, operations, cash flows, and liquidity and on the economy in general; interruptions in our supply chain, including due to potential effects of the COVID-19 pandemic on our operations and business in geographic locations impacted by the pandemic and on the business operations of our customers and suppliers; adequacy of and our ability to successfully execute and maintain the activities and efforts related to the measures we have taken or may take in response to the COVID-19 pandemic and associated costs therewith; effectiveness of our restructuring plan announced in December 2017; challenges associated with conducting business globally, including adverse effects of the COVID-19 pandemic, political or economic instability, major hostilities or terrorism; our ability to attract, hire and retain highly skilled personnel; our ability to develop and commercialize additional pharmaceutical products; compliance with anti-corruption sanctions and trade control laws; manufacturing or quality control problems; disruptions of information technology systems; breaches of our data security; variations in intellectual property laws; significant sales to a limited number of customers; our ability to successfully bid for suitable acquisition targets or licensing opportunities, or to consummate and integrate acquisitions; our prospects and opportunities for growth if we sell assets and potential difficulties related to the operation of our new global enterprise resource planning (ERP) system;
• compliance, regulatory and litigation matters, including: our ability to successfully defend against the DOJ criminal charges of a Sherman Act violations; increased legal and regulatory action in connection with public concern over the abuse of opioid medications in the U.S. and our ability to reach a final resolution of the remaining opioid-related litigation; costs and delays resulting from the extensive governmental regulation to which we are subject or delays in governmental processing time including due to modified government operations due to the COVID-19 pandemic and effects on product and patent approvals; the effects of reforms in healthcare regulation and reductions in pharmaceutical pricing, reimbursement and coverage; governmental investigations into S&M 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 Quarterly Reports on Form 10-Q for the first and second quarters of 2020 and our Annual Report on Form 10-K for the year ended December 31, 2019, including in the sections captioned "Risk Factors” and “Forward Looking Statements.” 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.

1. Data on file. Parsippany, NJ: Teva Pharmaceuticals USA, Inc.

2. AJOVY(fremanezumab-vfrm) injection Current Prescribing Information. North Wales, PA: Teva Pharmaceuticals USA, Inc.

* Study design: Of the patients who rolled over from the HALO studies, 611 from the HALO CM study (quarterly, n=306; monthly, n=305) and 432 from the HALO EM study (quarterly, n=217; monthly, n=215) had received AJOVY^® (fremanezumab-vfrm) injection during the respective HALO study and were included in post hoc analyses during the long-term, open-label extension study¹

⁺ “Long-acting” defined as efficacy measured over a 12-week period following a 675 mg (225 mg x 3) SC dose.²

^± 225 mg monthly administered as one subcutaneous injection, or 675 mg every three months (quarterly), which is administered as three subcutaneous injections.