A review of the current treatment drugs and modalities demonstrated that the established hypothesis of the CGRP panel in the therapy of migraine headaches is short on its translational efficacy. A critical look at the “Full prescribing information contents” reveals a lack of information about the mechanisms of action of those drug molecules! All is to convince of the short-term safety of their drugs. Where is the primary potential action tissue or cell?

The impact felt by market analysis is the continuous suffering of migraine headaches and further sales erosion throughout the industry as patients and investors tried to understand the long-term effect of biosimilar entry, particularly on the innocent pediatric population. A critical review of the literature revealed that over the past 20 years, scientists and pharmaceutical manufacturers have tried to convince the world of the therapeutic value of new biosimilars — CGRP monoclonal antibodies and receptor blockers —despite no significant therapeutic value for these biologics. In addition, this line of drugs made no difference to Triptans or Non-Steroidal Anti-Inflammatory Drugs. Effective marketing of daily flourishing new biosimilars on the market in scientific journals & conferences, television, and radio is far from the reality of effectively preventing and aborting migraine symptoms. Not even closer to a cure. Patients and physicians are astonished by the frequent modification of the treatment of migraine headaches by the defender of the CGRP hypothesis and their blooming monoclonal antibody products in the migraine treatment market. CGRP-related drugs do not demonstrate any action in the neuroinflammatory process, in neutralizing the TNF-α inhibition, or neutralizing the activated NF-κB anywhere in the central and peripheral nerve system. Utilization of CGRP drug lines is not suitable for the eradication and relief of migraine and cluster headaches. CGRP drugs, by in-depth analysis of their results, are unfit for the marketed scientific expectations. The reality proved that CGRP drugs are not advantageous to NSAIDs or triptans.

Non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin and ibuprofen, are routinely marketed for headache relief and belong to a class of medications known as cyclooxygenase (COX) inhibitors. These agents inhibit the activity of COX-1 and COX-2, enzymes pivotal in the biosynthesis of prostaglandins—lipid compounds that mediate inflammation, pain, and fever.

• COX-1: Constitutively expressed; involved in maintaining gastrointestinal and renal function.
• COX-2: Inducible; upregulated during inflammation and contributes to pain signaling.

By inhibiting these enzymes, Aspirin and Ibuprofen reduce prostaglandin synthesis. This leads to short-term analgesia and anti-inflammatory effects, particularly beneficial in conditions like craniofacial neuralgia, where localized inflammation in the vascular adventitia of neurons contributes to pain, which is manifested in the brain.

In the past decade, we recognized the discouraging failure of the CGRP and vasodilation hypotheses of migraine headaches and the subsequent monoclonal antibody drugs. Basically, this hypothesis and treatment modus failed because it did not provide the relief it claimed to. It is eliminating itself by failing to support its purpose. The enthusiasm of paid research scientists at universities flattened. There is no self-criticism or revisions in this hypothesis in the horizon.

The Scientific Premise- vs. Disillusionment

• Many patients report minimal or inconsistent relief despite high expectations and aggressive marketing.
• Real-world data, such as those from the VYEPTI® experience, show mixed outcomes: while some patients report improved quality of life, others continue to suffer frequent, debilitating attacks.
• Adverse effects like hypertension and Raynaud’s phenomenon have further eroded trust.

Physician Frustration

• Clinicians face pressure to prescribe CGRP therapies despite limited long-term data and variable patient responses.
• The hypothesis has arguably narrowed the therapeutic lens, sidelining other mechanisms and holistic approaches.

Media and Public Outcry

• Patients increasingly voice their dissatisfaction in public forums, questioning the scientific rigor and ethical transparency of pharma-led narratives.
• The disbelief stems not only from unmet expectations but also from the perception that industry-driven science has overshadowed patient-centered care.

The community’s response to the frequent introduction of new biosimilars is one of skepticism and disbelief. They look beyond the megalomaniac introduction of new routes of application and the decline in the results of biosimilars. This behavior is highlighted by the results showing a decrease in the prescribing of monoclonal antibodies by neurologists and primary care providers. The market has not been uniform across America and European countries.

One primary reason each country’s economy has been deprived of billions of dollars in the common health budget each year over the past decades is the sophisticated advertising of new biosimilars in the field of migraine headache. We live in real time, and this is thoroughly challenging for consumers’ economies and productivity. Yet, we believe in humanity more than industry. So, ultimately, we decided to share our knowledge by teaching and opening our expertise and discoveries to all headache communities to help resolve migraines and cluster headaches without extravagant financial gain. Our De-Novo model offers something radically different: freedom from recurrence, not just relief from pain.

Let’s stop experimenting with the lives of innocent people. Did we hurt anyone? Our apologies!

CURE MIGRAINE WORLDWIDE & RESEARCH, LLC.