Zavegepant nasal spray approved for acute migraine

15th March 2023

Zavegepant has become the first calcitonin gene-related peptide receptor antagonist nasal spray approved for the treatment of acute migraine.

Pfizer has announced that zavegepant has become the first calcitonin gene-related peptide receptor antagonist nasal spray to receive approval by the FDA for the management of acute migraine.

According to a study using data from 2016, it was estimated that globally, migraine affects some 1.04 billion people and caused 45·1 million years of life lived with disability. Although there was a breakthrough in treatment of migraine during the early 1990’s with the introduction of triptans, it later emerged that the calcitonin-gene-related peptide (CGRP) pathway was important in the pathophysiology of migraine.

While first generation drugs targeting this pathway, known as ‘gepants’ were effective, hepatotoxicity halted further development but did lead to new generation of gepants, which have been shown to be safe, efficacious and well tolerated.

Zavegepant clinical studies

Zavegepant nasal spray is a third generation gepant and the first, non-oral gepant. In a randomised, dose-ranging, placebo-controlled, phase 2/3 trial in adults aged ≥18 years with migraine, single doses of 10 or 20 mg, of the drug were shown to be effective for the acute treatment of migraine and with a favourable safety profile.

Further data on the efficacy of zavegepant and which formed the basis for the approval, came from a double-blind, randomised, placebo-controlled phase 3 trial in adults with a history of two to eight moderate or severe migraine attacks per month. 

The results showed that among those assigned to zavegepant, two hours after the treatment dose, a statistically significant higher proportion of zavegepant patients had freedom from pain and freedom from their most bothersome symptom.

In addition, twice as many patients (16% vs 8%) given zavegepant reported pain relief after only 15 minutes. There were also significant differences (compared to placebo) for 13 of the 17 pre-specified secondary outcomes.

The trial also found that the drug was well tolerated with the most common adverse reactions reported in at least 2% of patients and at a frequency greater than placebo, were taste disorders (includes dysgeusia and ageusia), nausea, nasal discomfort and vomiting.

RSVpreF vaccine candidate effective against respiratory syncytial virus

31st August 2022

RSVpreF a vaccine candidate against respiratory syncytial virus showed a high level of efficacy in older adults with more severe infection

Pfizer’s vaccine candidate RSVpreF for respiratory syncytial virus (RSV) showed a high level of efficacy in older patients with more severe lower respiratory tract illness which was defined by three or more RSV-associated symptoms.

RSV is a major viral pathogen causing severe lung disease in the adult population, particularly among the elderly and which constitutes a substantial disease burden. The global number of hospital admissions for RSV-ARI in older adults has been estimated to be 336,000 leading to about 14,000 in-hospital deaths.

Currently, there is no specific treatment for the virus apart from supportive care. RSV has two molecular subtypes A and B and RSVpreF is bivalent vaccine based on the crystal structure of pre-fusion F and which is a vital form of the viral fusion protein (F) that RSV uses to attack human cells. The vaccine itself contains two preF proteins which protect against the two main form of RSV, A and B which actually have multiple genotypes within each of them.

The phase 3 trial RENOIR is designed to assess the efficacy, immunogenicity and safety of RSVpreF in adults. While RENOIR is not complete, the release describes how to date, the trial has enrolled approximately 37,000 participants and who were randomised to receive 120μg RSVpreF or placebo in a 1:1 ratio. Enrolment up to approximately 40,000 participants continues in the Southern Hemisphere to accumulate cases during their first season.

A pre-planned, interim analysis was used to assess protection against RSV-associated lower respiratory tract illness defined by two or more symptoms. The analysis determined a vaccine efficacy of 66.7% (96.66% CI: 28.8% – 85.8%). 

Based on this positive result, Pfizer turned to the more severe disease primary endpoint defined by three or more symptoms and where the vaccine efficacy was 85.7% (96.66% CI: 32.0% – 98.7%). Moreover, an independent, external Data Monitoring Committee indicated the investigational vaccine was well-tolerated, with no safety concerns.

Commenting on these interim findings, Annaliesa Anderson, senior vice president and chief scientific officer, vaccine research and development at Pfizer said: ‘Scientists and researchers have worked to develop RSV vaccines with little success for over half a century. These findings are an important step in our effort to help protect against RSV disease.’

Pfizer is also investigating the efficacy and safety of RSVpreF in infants born to women vaccinated during pregnancy.