Finding a winner in VX-445, Vertex hustles CF combo to regulators on both sides of Atlantic
The verdict is in from Vertex’s clinical team.
The biotech was presented with a pleasant dilemma in March when a cocktail for cystic fibrosis mixing VX-445, tezacaftor and ivacaftor passed Phase III with flying colors, matching the results they got for VX-659 with the other two drugs, also known as Symdeko and Kalydeco. That left observers hanging as to which combo will head to regulators.
Vertex ultimately decided to go with VX-445 — after reviewing some more data it’s disclosing today.
At week 24 of treatment, patients with one F508del mutation and one minimal function mutation on the drug maintained absolute improvement in percent predicted forced expiratory volume in one second of 14.3% (p<0.0001). For a key secondary endpoint, the same group of patients saw a 63% reduction in the annualized rate of pulmonary exacerbations compared to placebo, with the same stellar p-value.
As previously reported, patients on the VX-445 triple had their ppFEV1 improve by an average of 13.8% at week 4. In a separate trial for VX-659, the number was 14%.
“People with CF who have one F508del mutation and one minimal function mutation are the largest remaining group of CF patients without a treatment option for the underlying cause of their disease,” CMO Reshma Kewalramani said in a statement.
The biotech further noted that the decision “was based on a detailed assessment of multiple factors, including favorable profiles for safety, tolerability and drug-drug interactions, the ability for co-administration with hormonal contraceptives, and the lack of photosensitivity.”
Vertex will now take these data, alongside another 4-week Phase III study CF patients with two F508del mutations, to the FDA in Q3 and then the EMA in Q4.
Credit Suisse analysts are fully on board with the plan, saying it signals a “clear path forward for the triple combo, with longer-term data supporting continued efficacy. We expect approval in 1H20, allowing the co. to treat 90% of CF pts WW. OUS reimbursement questions remain.”
Image: Vertex Pharmaceuticals