Teva announces new positive AJOVY®▼ (fremanezumab) real world data from its migraine prevention study, PEARL and welcomes updated European Headache Federation guidelines on the use of CGRP mAbs

• Real-world observational study data presented at Migraine Trust International Symposium (MTIS) demonstrate sustained effectiveness of AJOVY▼(fremanezumab) in reducing migraine attacks^[i]
• Data from various real world observational studies have been incorporated in the recent update to the European Headache Federation’s (EHF) migraine guideline which now suggests the use of calcitonin gene related peptide pathway monoclonal antibodies (CGRP-mAbs) as first-line rather than third-line treatment for migraine prevention^[ii]

Amsterdam, Netherlands, 8^th September 2022: Teva Pharmaceuticals Europe B.V. today announces further positive AJOVY▼ (fremanezumab) interim results¹ from its Pan-European Real World study (PEARL),^[iii] presented at the Migraine Trust International Symposium (MTIS) in London, UK.  AJOVY▼ (fremanezumab) is indicated for the prevention of migraine in adults with at least 4 migraine days per month.^[iv]

The PEARL 2^nd interim analysis¹ shows that more than half of patients (56%) with episodic or chronic migraine included in the study had their monthly-migraine-days (MMDs) reduced by 50% or more over the six month period from the start of treatment with fremanezumab. The analysis showed that the mean change in MMDs was -8 days at Month 6, -8.5 days at Month 9 and -8.3 days at Month 12.¹

These positive outcomes in the 2^nd interim analysis¹ are important as it shows treatment effectiveness in larger patient numbers (n=574) and for longer treatment duration (up to 12 months) compared to the 1^st interim analysis (n=389 / up to 9 months).^[v]

The study may also be particularly relevant to clinicians due to its broad and diverse patient cohort, who come from 11 countries and 87 study centers. The patient group includes migraine patients with various comorbidities, multiple previous preventive treatments and also a range of reimbursement settings which is important for treatment access in Europe.  

Real world data from various observational studies conducted in relation to the use of CGRP-mAbs has supported the consensus laid out in the latest European Headache Federation (EHF) guideline²  published in June 2022.

According to these new guidelines: “After the publication of the previous guidelines, CGRP mAbs became available in Europe and real-world observational studies confirmed the effectiveness of those drugs outside randomized clinical trials (RCTs). Tolerability and safety profiles were confirmed to be excellent and the adherence to treatment was not reported as a critical issue as it was with oral treatments”. ²

Within the Expert Consensus Statements the Guideline Committee now suggests that CGRP mAbs may be used as a first line treatment option for migraine prevention. The authors state: “There are no reasons on clinical grounds to postpone the initiation of this treatment. However, first line treatment option should be carefully chosen by physicians considering the patient’s history, comorbidities, and burden of the disease. Headache experts must be able to choose, after discussion with the patient, the therapy that is most appropriate”. ²

Furthermore, the Expert Consensus Statement within the guideline supports longer treatment duration with CGRP mAbs. In the earlier EHF guideline (2019),^[vi]  treatment duration had been recommended for 6-12 months before a treatment pause. The EHF 2022 guideline suggests considering a pause after 12-18 months of continuous treatment and if deemed necessary, treatment should be continued as long as needed.²

PEARL, a 24-month study³, should shed more light on how patients respond to fremanezumab in the long term in a real world setting in Europe and how they are affected by stopping and restarting their treatment.

Commenting on the PEARL study findings, Professor Messoud Ashina, PEARL Coordinating Investigator from the Danish Headache Center and Department of Neurology in Rigshospitalet Glostrup, Denmark and one of the authors of the EHF migraine guideline said: “In this second analysis from the PEARL study, we see further evidence of fremanezumab effectiveness in a large number of patients from multiple countries.
The real world effectiveness and safety profile of CGRP mAbs has contributed to the guideline’s recommendation for earlier use of this class of medicines in the prevention of migraine.”

Dr. Danilo Lembo, Vice President Medical Affairs Teva Europe, said: “Teva welcomes the recent update of the EHF guideline where expert consensus has resulted in important recommendations for migraine prevention. Over the 24 month duration of the PEARL study, further data aims to shed light on the long term effectiveness of fremanezumab in real world clinical practice. Currently, access to preventive migraine treatments in Europe is not optimal with a recent study from the European Migraine and Headache Alliance showing that 40% of patients needed more than five years to access migraine treatments.^[vii]   Further changes are needed in healthcare systems to reduce the burden of migraine.”

References:

[i] Ashina et al. Effectiveness of Fremanezumab for the Preventive Treatment of Migraine: Second Interim Analysis of the Observational PEARL Study. Presented at the Migraine Trust International Symposium (MTIS); 8-11 September 2022; London, United Kingdom. MTIS-PO-054

[ii] Sacco et al. European Headache Federation guideline on the use of monoclonal antibodies targeting the calcitonin gene related peptide pathway for migraine prevention – 2022 update. The Journal of Headache and Pain (2022) 23:67. https://doi.org/10.1186/s10194-022-01431-x

[iii] Ashina et al. PEARL study protocol. The two year Pan-European Real World (PEARL) prospective, observational study of AJOVY® (fremanezumab). Pain management, 11(6), 647–654. (v0.1)

[iv] Ajovy EU SmPC  https://www.ema.europa.eu/en/documents/product-information/ajovy-epar-product-information_en.pdf [last accessed 31 Aug 2022]

[v] Ashina et al. Effectiveness of fremanezumab for preventive treatment of migraine: the observational PEARL study. Presented at the 8th Congress of the European Academy of Neurology (EAN); Vienna, Austria 2022 June 25-28. EPR-035

[vi] Sacco et al. European headache federation guideline on the use of monoclonal antibodies acting on the calcitonin gene related peptide or its receptor for migraine prevention. The Journal of Headache and Pain (2019) 20: 20:6  https://thejournalofheadacheandpain.biomedcentral.com/articles/10.1186/s10194-018-0955-y#Sec33

[vii] KPMG, prepared for the European Migraine and Headache Alliance (EMHA). “Access to Care” project: final assessment. July 2021. [online] Available at: https://www.emhalliance.org/wp-content/uploads/ATC-EMHA-Dossier.pdf [last accessed 31 Aug 2022]