Elexacaftor/Ivacaftor/Tezacaftor

Vertex's next-gen cystic fibrosis treatment is a once-daily triple CFTR modulator regime. Vertex Pharmaceuticals is ahead of schedule, filing a new drug application for its next-gen cystic fibrosis (CF) treatment dubbed vanza triple. Vertex completed the regulatory submission a month before its goal of mid-2024, CEO Reshma Kewalramani, M.D., said on a first-quarter earnings call May 6. The investigational treatment is a once-daily triple CFTR modulator regimen made up of vanzacaftor, tezacaftor and deutivacaftor. Earlier this year, vanza triple achieved the main goals across several phase 3 programs, demonstrating noninferiority against Vertex’s own twice-daily Trikafta for improving lung function and superiority to Trikafta in lowering levels of sweat chloride. Now, Vertex is asking for the FDA to approve vanza triple for people with CF aged 6 years and older. The Boston-based company also completed a submission in Europe for the same indication and is on track to complete submissions in the U.K., Canada, Australia, New Zealand and Switzerland, Kewalramani said. In the U.S., Vertex intends to use its FDA priority review voucher, which guarantees an expedited six-month review process. Other big updates from the biotech include resumed enrollment in a phase 1/2 diabetes trial, which is evaluating an allogeneic, stem cell-derived insulin-producing islet cell therapy dubbed VX-880. Vertex implemented a voluntary hold on the trial back in January after two deaths deemed unrelated to treatment occurred. After an independent data monitoring committee reviewed data from the trial, Vertex has resumed dosing and completed enrollment of 17 patients who have Type 1 diabetes with impaired hypoglycemic awareness and severe hypoglycemia. The company expects to finish dosing soon. Vertex plans to share updated data on the cell therapy—which has previously shown promise in eliminating the need for insulin in a small group of patients—at the American Diabetes Association Scientific Sessions conference in June. The two updates come a few weeks after Vertex announced plans to sell autoimmune and inflammatory disease-focused Alpine Immune Sciences for $4.9 billion. The transaction is expected to close in the second quarter of this year.

Vertex Pharmaceuticals said that since gaining the first approvals late last year for Casgevy (exagamglogene autotemcel), five patients have had stem cells collected as of mid-April in preparation for manufacturing of the gene therapy. Stuart Arbuckle, chief operating officer, called the progress “excellent,” noting that “many patients have [also] begun the treatment journey” in the markets where Casgevy is approved, which include the US, Europe and the Middle East.The therapy, which utilises CRISPR/Cas9 gene-editing technology and carries a list price of $2.2 million in the US, is authorised for use in patients with sickle-cell disease (SCD) and transfusion-dependent beta thalassaemia. Arbuckle, speaking on the company’s first-quarter earnings call, explained that the cell collections have occurred across all regions where Casgevy is available.Meanwhile, bluebird bio recently said it completed the first commercial cell collection for its cell-based gene therapy Lyfgenia (lovotibeglogene autotemcel). The product is approved in the US, where it has a list price of $3.1 million and is used to treat SCD patients with a history of vaso-occlusive events. Both Casgevy and Lyfgenia gained clearance from the FDA last December.Casgevy ‘ramping more quickly’Mizhuo analysts noted that Casgevy “seems to be ramping more quickly” than Lyfgenia, particularly in the US, in terms of cell collections-to-treatment centres. According to the analysts, Vertex and co-development partner CRISPR Therapeutics have 18 active collection sites in the US, while bluebird has over 60 centres.Globally, Vertex says it has activated more than 25 authorised treatment centres (ATCs) for Casgevy, with a target of bringing 75 priority centres online. Analysts at Morgan Stanley forecast that a total of 80 patients will receive Casgevy in 2024, including 54 in the US.Revenue in second halfArbuckle indicated that the drugmaker continues to “make great progress with payers,” although he reiterated that it will only “recognise revenue…near the end of the patient journey at infusion.” Vertex is including Casgevy revenue in its overall annual sales forecast of $10.55 billion to $10.75 billion, with the gene therapy contributing in the second half of the year. However, the company’s cystic fibrosis (CF) products are still set to generate the majority of sales.In the first quarter, the drugmaker’s product revenue increased 13% to $2.7 billion, topping estimates of $2.6 billion, led by $2.5 billion in sales of the CF treatments Trikafta and Kaftrio. Meanwhile, net income reached $1.1 billion, up from around $700 million in the prior year.Pipeline in focusDavid Song of Tema ETFs remarked "over the next 12 to 18 months, investors are evaluating whether Vertex can sustain its CF franchise for several years and expand upon it through internal pipeline development, as well as business development." The company recently agreed to buy Alpine Immune Sciences for $4.9 billion, gaining the experimental drug povetacicept for IgA nephropathy.Vertex is also hoping to bring a non-opioid pain drug to market, having initiated an FDA rolling submission for suzetrigine, while its other pipeline bets include inaxaplin in autosomal dominant polycystic kidney disease and VX-880 in type 1 diabetes. For related analysis, see Vital Signs: Dissecting dealmaking at Vertex and its Alpine takeout.