Vertex wagers $4.9bn on Alpine kidney disease therapy

In another departure from its core focus on genetic medicines, Vertex Pharma has agreed a $4.9 billion purchase of Alpine Immune Sciences, adding a mid-stage drug candidate for kidney disease IgA nephropathy (IgAN).

The $65-per-share deal is due to close within the next three months, said Vertex, which plans to fund the acquisition with cash in hand. It is the largest acquisition in the biopharma sector so far in 2024, and Vertex's largest to date.

Vertex’s move has been announced at the same time that Alpine shared new data for the IgAN candidate – povetacicept (ALPN-303) – a dual antagonist of the BAFF and APRIL cytokines that Vertex reckons could be a ‘pipeline-in-a-product’ with potential in other indications, including lupus nephritis and autoimmune cytopenias.

It is due to advance into phase 3 later this year for IgAN, a rare autoimmune kidney disorder and a leading cause of kidney failure, in which antibodies accumulate in the kidneys causing inflammation and scarring. The disease affects around 130,000 people in the US and another 115,000 in Europe.

The new results from the phase 1b/2a RUBY study in 41 IgAN patients showed that povetacicept given by subcutaneous injection at a dose of 80 mg once every four weeks achieved a 64% reduction in proteinuria, a surrogate marker for impaired kidney filtration. Out of six evaluable patients on that dose, four achieved remission and stable kidney function. A higher 240 mg dose achieved similar results.

Vertex’s move for Alpine marks a turnaround in the fortunes for the company, which was looking vulnerable in 2022 when it was forced to abandon its lead cancer immunotherapy davoceticept due to patient deaths in trials.

It switched its focus to autoimmune and inflammatory diseases, led by povetacicept and AbbVie-partnered dual CD28 and ICOS inhibitor acazicolcept, which is in a phase 2 lupus trial, with results due later this year.

Vertex has built its business on genetic medicines for cystic fibrosis, which generated almost $10 billion in revenues last year, and recently added to its portfolio with a therapy for blood disorders sickle cell disease (SCD) and transfusion-dependent beta thalassaemia. It has broadened its R&D focus in recent years to include protein-based therapeutics across multiple indications.

In the kidney disease category, its pipeline includes inaxapalin (VX-147) for APOL1-mediated kidney disease, in phase 3, and early-stage candidate VX-407 for autosomal dominant polycystic kidney disease.

Bank of America analysts said in a research note that the deal “adds strategic value and further bolsters Vertex’s long-term growth profile,” and is an example of the company “putting its money to good work” at a time when investors have been looking for business development.

They note that competition in IgAN will be fierce, as several BAFF and/or APRIL inhibitors could launch ahead of povetacicept, including Novartis/Chinook’s zigakibart, Otsuka/Visterra’s sibeprenlimab, and Vera Therapeutics’ atacicept, which are already in phase 3 and so one to two years ahead in development.

That said, they believe Alpine’s drug has best-in-class potential as a result of superior BAFF/APRIL inhibition, backed by its convenient dosing regimen.

Photo by Simon Fitall on Unsplash