Zavegepant is an investigational drug that is currently in development to treat migraines ( Pfizer ). In March 2023, it obtained marketing authorization from the FDA, the American health agency. It belongs to a class of drugs called calcitonin receptor antagonists (CGRP).
Why target CGRP?CGRPs are proteins that play a key role in the transmission of pain and inflammation. This protein is massively released at the level of the meninges (the envelope of the brain) during a migraine attack. CGRP receptor antagonists, such as zavegepant, block the action of these proteins to reduce the frequency and severity of migraines.
To learn more about CGRP in migraine , you can read our dedicated article.
What are the differences between a CGRP antagonist and an antibody directed against CGRP?CGRP receptor antagonists and CGRP antibodies are two different types of migraine treatments that both target CGRP. However, they act in different ways:
- CGRP receptor antagonists are drugs that block CGRP receptors in the brain and blood vessels. By blocking the receptors, these drugs prevent CGRP from binding and triggering migraines. CGRP antagonists are small molecules that can be administered orally or by injection.
- Antibodies to CGRP are biological drugs that specifically target CGRP itself. These drugs are antibodies produced by immune cells that bind to CGRP and prevent it from causing migraines. Antibodies against CGRP are given by subcutaneous injection and have a longer duration of action than CGRP receptor antagonists.
Summary of the clinical study of Zavzpret (zavegepant)Link to the clinical study: " Zavegepant nasal spray for the acute treatment of migraine: A Phase 2/3 double-blind, randomized, placebo-controlled, dose-ranging tria l":
Goal of the study :
The objective of this study was to assess the efficacy, safety and optimal dose of Zavegepant, a nasal spray for the acute treatment of migraine.
Researchers conducted a phase 2/3, randomized, double-blind, placebo-controlled study evaluating different doses of Zavegepant (5, 10 or 20 mg) in 665 patients with moderate to severe migraine. Patients received study treatment or placebo within two hours of migraine onset.
The results showed that all three doses of Zavegepant were superior to placebo in relieving migraine pain two hours after taking the treatment. Pain relief was significantly greater in patients who received the 20 mg dose of Zavegepant compared to the 5 and 10 mg doses. Zavegepant also showed significant improvement in symptoms associated with migraine, such as nausea and sensitivity to light and sound, compared to placebo.
The most common side effects were burning and tingling sensations in the nose, as well as headaches. No serious adverse events were reported.
Conclusion of the study:
The study authors concluded that Zavegepant was effective and safe for the acute treatment of migraine, with a 20 mg dose showing greater efficacy than lower doses. They noted that further studies are needed to confirm these results and to assess the long-term use of Zavegepant in patients with migraine.
The limits of the ZavegepantLike any drug treatment, zavegepant has limitations. Here are some of the potential limitations of this treatment:
- Variable effectiveness : Although clinical trials have shown zavegepant to be effective in treating acute migraines, effectiveness may vary from person to person. Some patients may not respond to treatment or experience significant symptom relief.
- Side effects : As with any medication, zavegepant can cause unwanted side effects, such as nausea, dizziness, and fatigue. Although these side effects are generally mild, they can be bothersome for some patients. The effects for long-term use are still unknown.
- Cost : As zavegepant is a new drug, it is likely to be expensive when it becomes available on the market. This could limit access to treatment for some patients. This is the case for antibodies directed against CGRP, for example.
- Limited availability : The zavegepant is not yet approved in Europe. There is still a long way to go before we find it in our pharmacies. Like antibodies to CGRP, it is likely to be reserved for a certain type of patient in the first place.
Ultimately, the choice of treatment for migraine will depend on each patient's medical history and individual situation. It is important to discuss the benefits and limitations of each treatment with your doctor to determine the most appropriate treatment for you.
Efficacy and safety questions still outstandingThe main questions around this drug include:
- Effectiveness: Is zavegepant effective in relieving migraine symptoms, including pain and nausea?
- Safety: Does zavegepant have any significant side effects or long-term health risks?
- Comparison with other treatments: How does zavegepant compare with other treatments available for migraine, such as triptan medications or CGRP monoclonal antibodies?
- Dosage and dosage: what is the optimal dose of zavegepant and what is the best way to administer it?
- Access and cost: Will zavegepant be accessible and affordable for people with migraines? How much will it cost compared to other treatments?
These questions are currently the focus of research and clinical studies to better understand the potential benefits and risks of zavegepant as a treatment for migraine.