Teva Halts Ajovy Development for Cluster Headache Amid Disappointing Phase III Results

Because the futility analysis of the Phase III ENFORCE study in patients with episodic cluster headache indicated that the drug was unlikely to meet the primary endpoint—the mean change from baseline in the average number of weekly cluster headache attacks during the 4-week treatment period—Teva announced on April 23 that it is discontinuing the clinical development program for fremanezumab (brand name Ajovy) for the treatment of cluster headache.

It is reported that the program also includes a long-term safety study and a previous study on chronic cluster headache. The chronic cluster headache study was discontinued in June 2018, but research into other indications for fremanezumab continues, including the treatment of post-traumatic headache (currently under investigation in Phase II clinical trials).

Dr. Tushar Shah, Senior Vice President and Global Head of Professional Clinical Development at Teva, stated, “We thank the patients and researchers for their significant contributions to this study. Despite the current results, we continue to evaluate whether fremanezumab treatment may provide clinical benefits for other conditions, given the role of anti-calcitonin gene-related peptide (CGRP) therapy in pathophysiology.”

Fremanezumab is a humanized monoclonal antibody that binds to the calcitonin gene-related peptide (CGRP) ligand and blocks its interaction with receptors. It has been studied for the treatment of cluster headaches or post-traumatic headaches. On September 14, 2018, the U.S. FDA approved Ajovy (fremanezumab-vfrm) injection, developed by Teva Pharmaceutical Industries Ltd. of Israel, making it the second CGRP monoclonal antibody approved globally. This medication is administered via monthly or quarterly injections for the preventive treatment of migraine in adults.

Anti-CGRP Market: Ajovy’s Future Looks Bleak

On December 17, 2018, Teva announced positive results from the Phase IIIb FOCUS clinical study, which evaluated the efficacy and safety of fremanezumab for the preventive treatment of migraine in adult patients. This was the first study conducted in patients with both chronic and episodic migraine, demonstrating the drug’s efficacy in a patient population that is difficult to treat and requires additional therapeutic options. (See: Teva Announces Latest Phase IIIb Clinical Results for CGRP Inhibitor in Migraine Prevention)

Yet such brilliance seems unable to offset the looming shadows facing Ajovy. Over the past year and a half, Teva has undergone a painful restructuring. According to Endpoint News, a foreign media outlet, the approval of Ajovy marked one of the company’s rare R&D highlights. The recent failure in the study on episodic cluster headache may deliver another blow to Teva, further narrowing the marketing scope for this migraine medication.

Geoffrey Porges, an analyst at Leerink, previously forecast that the anti-CGRP migraine drug market would reach total sales of $6.89 billion by 2025, with Aimovig (erenumab, Amgen/Novartis), the first FDA-approved drug in this class, ranking first with $2.87 billion in sales and capturing a 40% market share, while Ajovy and Emgality (galcanezumab, Eli Lilly) competed for second place. However, on October 17, 2018, Express Scripts (ESI) included Aimovig and Emgality in its list of recommended anti-CGRP migraine drugs while excluding Ajovy, a move that undoubtedly marginalized Ajovy in the U.S. market and hindered its sales growth.

Industry insiders stated that Teva’s losses in this therapeutic area are likely to become gains for its competitors. Eli Lilly has recently submitted a priority review application for Emgality for the treatment of cluster headache and has already obtained some positive clinical data.

Meanwhile, the anti-CGRP market is seeing an influx of additional competitors. On March 11, 2019, Allergan submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for ubrogepant for the treatment of acute migraine in adults, with a Prescription Drug User Fee Act (PDUFA) target date in the fourth quarter of 2019. This drug could become the world’s first oral small-molecule CGRP antagonist for migraine. On March 13, Biohaven announced that it would submit an NDA to the FDA for its oral small-molecule CGRP antagonist rimegepant in the second quarter of 2019, expecting it to become the second such oral therapy globally.

On April 22, Alder BioPharmaceuticals announced that the FDA had accepted the Biologics License Application (BLA) for eptinezumab for the prevention of migraine. If approved, the drug would be launched in the first quarter of 2020 and become the first quarterly intravenous infusion therapy for migraine prevention.

In such a crowded competitive landscape for anti-CGRP drugs, Teva’s clinical trial failure in one migraine indication could result in the loss of a market worth hundreds of millions, or even billions, of dollars in the future.

Article reference:

Teva Announces Update on Fremanezumab Clinical Development for use in Episodic Cluster Headache

https://www.businesswire.com/news/home/20190423005570/en/Teva-Announces-Update-Fremanezumab-Clinical-Development-Episodic/

U.S. Food and Drug Administration Accepts Biologics License Application for Eptinezumab

https://www.tmcnet.com/usubmit/2019/04/22/8942551.htm

FDA Accepts Biologics License Application for Eptinezumab in the Prevention of Migraine

https://med.sina.com/article_detail_103_1_64947.html

2018: Antibody Drugs Achieve Significant Success in the Migraine Field as CGRP Receptor Antagonists Challenge the Market

https://med.sina.com/article_detail_103_1_56658.html

Aimovig and Emgality Listed on ESI Preferred Drug Formulary

https://med.sina.com/article_detail_103_2_54533.html

World’s First CGRP Small-Molecule Migraine Drug Ubrogepant Submits Marketing Application

https://med.sina.com/article_detail_103_2_62708.html

FDA Accepts Biologics License Application for Eptinezumab in the Prevention of Migraine

https://med.sina.com/article_detail_103_1_64947.html

Source: Sina Medical News