Trikafta starts it EMA Journey
Vertex has submitted a marketing authorization application to the European Medicines Agency (EMA) for Trikafta.
Trikafta is Vertex’s first triple combination therapy and includes elexacaftor (VX-445), plus tezacaftor, and ivacaftor (Kalydeco) — approved for use in CF patients, age 12 and older, with one F508del and one minimal function mutation, or with two F508del mutations
The FDA’s October decision to approve the therapy came in record time, five months ahead of the expected deadline of March 2020. Hot on the heels of this decision Vertex have submitted Trikafta to the European Medicines Agency (EMA) and this application (the first step on the road to final approval) has been accepted by the EMA. It is to be hoped that the EMA will give similar accelerated approval (provided all safety checks are made) which could make Trikafta available in Ireland sometime in the 2nd or 3rd quarter of 2020, all going well.
The following additional notes are drawn from a recent interview with the CEO of Vertex, Dr Leiden:
According to the CEO of Vertex: Trikafta’s approval was based on data from two Phase 3 clinical trials in the AURORA F/MF programme with patients who have one F508del mutation; and the AURORA F/F with those who have two F508del mutations.
The AURORA F/MF included 403 CF patients who were treated with Trikafta or placebo for up to 24 weeks. In the AURORA F/F, 107 patients with two F508del mutations received either Trikafta or Symdeko for four weeks.
Data from both studies showed significant improvements in lung function in people given Trikafta, as assessed by the percent predicted forced expiratory volume in one second (FEV1, a widely used measure of lung function)
The ppFEV1 increased by an average of 13.8 percentage points in the 24-week trial, and by 10 percentage points in the four-week trial.
Trikafta’s impact on patients’ health-related quality of life (HRQoL) was evaluated with the Cystic Fibrosis Questionnaire-Revised (CFQ-R), which incorporates general assessments, vitality, health perceptions, and physical, emotional, social and role functioning, as well as domains specific to CF (body image, eating, treatment burden, and respiratory and digestive symptoms).
According to the CEO of Vertex ‘our Phase 3 trial of Trikafta, we saw a 20-point improvement in CFQ-R, which is really unprecedented in these medical trials. So, that’s telling us that the patients’ own assessment of their lives has changed dramatically,’.
The benefits of Trikafta also were seen in the rate of pulmonary exacerbations, which often require patients to be hospitalized and risk losing lung function.
CEO of Vertex said in his recent interview ‘We saw a 63% reduction in pulmonary exacerbations, so that’s a dramatic clinically and statistically significant reduction in the major complications…In addition, we hear lots of stories from patients about how their daily life functions have been fundamentally changed by the medicine.’
In relation to patients switching from their current CFTR drug (if on one) Vertex have stressed ‘this is a decision between patients and doctors, and whether patients are satisfied with their current treatment with Symdeko or Orkambi’.
The CEO of Vertex emphasised ‘About 10% of CF patients remain without an available therapy, since they don’t make any CFTR protein. So, ‘there’s no combination of corrector therapies that will actually treat their disease because there’s no protein to treat,’.
Philip Watt, CEO of CFI adds,
‘While this is all in general very good news, it shows there remains much to do. We need to ensure that all eligible patients will be considered for Trikafta in Ireland once it is available (and with the advice of clinicians in respect of switching at individual patient level). It is also why we need continued high international and national investment in research to ensure we have additional therapies for those patients for whom CFTR drug therapies will have no impact (Kalydeco, Orkambi, Symdeco and Trikafta). In this context CFI remains determined ‘no one left behind’.