New Study Published in Cephalalgia Identifies Mechanistic Differences Among CGRP Migraine Treatments

In vitro findings suggest specific classifications for calcitonin gene-related peptide (CGRP) pathway-based therapeutics based on mechanisms

TEL AVIV, Israel--(BUSINESS WIRE)-- Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA)highlights results from the in vitro study “Migraine Therapeutics Differentially Modulate the CGRP Pathway,” which were published online by Cephalalgia, a monthly journal published on behalf of the International Headache Society. These results will also be featured in a future print issue of the journal. This study demonstrated marked differences in the mechanism of blocking the calcitonin gene-related peptide (CGRP) ligand versus the CGRP receptor.

This newly-published study evaluates three distinct mechanistic classes of drugs based on receptor binding, signaling and drug internalization: (1) Monoclonal antibodies against the CGRP ligand, (2) The monoclonal antibody against the CGRP receptor and (3) ‘Gepants’, small molecule inhibitors of the CGRP receptor.

“This in vitro study explored these mechanistic differences by comparing the tested compounds in the same experimental analyses, and found that the different ways to target the CGRP pathway may have a different biologic impact,” said Steffen Nock, Senior Vice President of Global Biologics, Teva. “For instance, fremanezumab in particular, as a monoclonal antibody against the CGRP ligand, is targeted and specific in its mechanism.”

AJOVY® (fremanezumab-vfrm) injection is a fully humanized IgG2ΔA monoclonal antibody that specifically and solely targets CGRP, a key neuropeptide involved in the pathophysiology of migraine. Since 2018, multiple CGRP pathway-based therapeutics have been approved by the U.S. Food and Drug Administration (FDA). These in vitro study data indicate that CGRP receptor targeting therapeutics bind at multiple receptors and prevent the subsequent signaling of several peptides, while AJOVY selectively binds to only CGRP, suggesting that its mechanism is specific while other receptor targeting treatments have potential for an off-target binding.

Importantly, this in vitro research found that an agent that targets the CGRP receptor versus the ligand, also bind to the human amylin AMY1 receptor, affecting signaling and undergoing internalization at both receptors suggesting a potential difference in their biologic function.

Clinical implications of these findings are unknown, but the in vitro studies provide insights into potential mechanistic differences. This study was supported by Teva, and all authors are full-time Teva employees.

AJOVY is the first and only long-acting anti-CGRP subcutaneous injection approved in the U.S. and EU for the preventive treatment of migraine in adults that offers both quarterly and monthly dosing options.1+±

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 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

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; delays in launches of new generic products; the increase in the number of competitors targeting generic opportunities and seeking U.S. market exclusivity for generic versions of significant products; our ability to develop and commercialize biopharmaceutical products; competition for our specialty products, including AUSTEDO®, AJOVY and COPAXONE®; our ability to achieve expected results from investments in our product pipeline; our ability to develop and commercialize additional pharmaceutical products; 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; 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 optimization efforts; our ability to attract, hire and retain highly skilled personnel; manufacturing or quality control problems; interruptions in our supply chain; disruptions of information technology systems; breaches of our data security; variations in intellectual property laws; challenges associated with conducting business globally, including political or economic instability, major hostilities or terrorism; costs and delays resulting from the extensive pharmaceutical regulation to which we are subject or delays in governmental processing time due to travel and work restrictions caused by the COVID-19 pandemic; the effects of reforms in healthcare regulation and reductions in pharmaceutical pricing, reimbursement and coverage; 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; and our prospects and opportunities for growth if we sell assets;
  • compliance, regulatory and litigation matters, including: failure to comply with complex legal and regulatory environments; increased legal and regulatory action in connection with public concern over the abuse of opioid medications and our ability to reach a final resolution of the remaining opioid-related litigation; scrutiny from competition and pricing authorities around the world, including our ability to successfully defend against the U.S. Department of Justice criminal charges of Sherman Act violations; potential liability for patent infringement; product liability claims; failure to comply with complex Medicare and Medicaid reporting and payment obligations; compliance with anti-corruption sanctions and trade control laws; 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 this press release and in our Annual Report on Form 10-K for the year ended December 31, 2020, 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. AJOVY (fremanezumab-vfrm) injection, for subcutaneous use [prescribing information]. Teva Pharmaceuticals USA, Inc.: North Wales, PA; 2020.
    + “Long-acting” defined as efficacy measured over a 12-week period following a 675 mg (225 mg x 3) SC dose.
    ± 225 mg monthly administered as one subcutaneous injection, or 675 mg every three months (quarterly), which is administered as three subcutaneous injections.

IR Contacts
United States
Kevin C. Mannix (215) 591-8912

Yael Ashman 972 (3) 914-8262

PR Contacts
United States
Doris Li (973) 265-3752

Yonatan Beker 972 (54) 888 5898

Source: Teva Pharmaceutical Industries Limited

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