Migraine Treatment of the Month: A Vyepti “Real World” Update
Epitenzumab (Vyepti) was highlighted in this magazine as a “migraine treatment of the month” in the Fall 2022 issue. To summarize, Vyepti is an anti-CGRP monoclonal antibody that, in the manner of a good marriage, binds long and with powerful attraction to the CGRP protein molecule; this binding prevents CGRP from docking with its receptor within the migraine circuitry and consequently “rheostats down” the sensitivity of that circuitry and so reduces headache production. To stretch the analogy even further, Vyepti and the CGRP protein molecule to which it binds so strongly require only a very short engagement before the marriage commences. Because the medication is infused intravenously (every three months), it is 100% “bioavailable” immediately post-infusion. In summary, then, Vyepti is designed to have high selectivity specifically for the CGRP molecule, strong and prolonged binding to that molecule and a rapid onset of that binding process.
So how did Vyepti perform in clinical research trials involving individuals with migraine? The PROMISE-1 and PROMISE–2 studies clearly established Vyepti to be safe, well-tolerated and effective for migraine prevention in research subjects with episodic migraine (PROMISE-1) and chronic migraine (PROMISE-2). In the chronic migraine study more than 60% of the patients randomized to Vyepti had experienced at least a 50% reduction in their migraine burden by 3 months following their initial infusion treatment. Testifying to the rapidity of the medication’s action, separation from placebo was observed as early as 1 day following the initial infusion. While research subjects randomized to Vyepti continued to experience an improvement in their migraine over the six months of study, the most striking decline in headache occurred early on, during the first month following the initial infusion. The only adverse reactions that occurred more commonly in the research subjects receiving Vyepti versus those receiving placebo were nasopharyngitis or related to hypersensitivity. In short, Vyepti appeared to be a remarkably “clean” therapy in terms of its side effect profile.
These large-scale phase 3 trials which earned Vyepti its FDA approval for the treatment of episodic and chronic migraine were meticulously conducted by experienced clinical investigators. How does Vyepti hold up when it is used as a treatment for migraine prevention in the “real world”? It is in the “real world” of clinical practice, where the “science” of medicine smacks head-on with the “art” of medicine, that we learn really how much or how little a new addition to the therapeutic arsenal will mean to us, the healthcare providers, and to our patients. If unexpected side effects, hurdles erected by insurance companies more intent on the financial bottom line than their clients’ best medical interests or one of the countless other issues that can arise serve to dim the luster of a new treatment when one leaves the rarified atmosphere of clinical research for the day-to-day slog of clinical practice, the pragmatic usefulness of a new treatment can diminish considerably.
The REVIEW study was conducted specifically to determine just how well Vyepti would hold up as a new treatment for the suppression of chronic migraine. In REVIEW, 94 adult participants with chronic migraine were treated with at least two consecutive Vyepti infusion cycles. These patients all had previously tried and failed prevention therapies intended to reduce their migraine burden, and the great majority (89%) previously had tried one of the subcutaneously self-injected anti-CGRP monoclonal antibodies. In other words, this was a tough group of chronic migraine patients who were hardly treatment-naïve and thus inclined to respond to any reasonable treatment intervention. They were not “cherry-picked” so as to make Vyepti look good.
So what happened? The average number of “good days” per month prior to initiation of treatment with Vyepti was 8, and this increased to 18 after Vyepti was begun. The majority of the participants were over-using either prescription or over-the-counter medication for acute migraine treatment prior to beginning Vyepti. After starting Vyepti nearly 2/3rds of those patients no longer were over-using symptomatic medication.
Perhaps most interesting to the author of this article, prior to beginning Vyepti 80% of the participants reported “brain fog”, and following initiation of treatment that symptom improved in 86%. Until he began helping with the clinical development of topiramate (Topamax) for migraine prevention in the early 2000s, the author had never heard the term “brain fog” used by patients. Topiramate clearly can produce a variety of cognitive side effects that many patients rapidly came to refer to as “brain fog”, and the term literally assumed epidemic proportions with the arrival of Covid. Topiramate and Covid aside, many patients with chronic migraine describe impaired cognition, and typically that impairment resolves in parallel was successful treatment of their chronic migraine. To the authors knowledge, REVIEW represents the first migraine treatment study wherein “brain fog” was included as an outcome variable to be examined, and it is extremely good news to learn that Vyepti may be helpful in dissipating that “fog”.
The “real world” verdict? Vyepti is a safe and extremely well-tolerated prevention therapy for high frequency episodic migraine and chronic migraine which substantially reduces migraine burden in a high percentage of patients and often begins to do so quite rapidly after initiation of treatment. It even appears to reduce or eliminate the “brain fog” which may complicate chronic migraine! In his clinical practice the author/editor considers Vyepti to represent a 1st line therapy for suppression of chronic migraine.