With largest acquisition to date, Vertex hopes for another blockbuster

Vertex Pharmaceuticals executive chairman Jeffrey Leiden has a few blockbuster drugs under his belt. Trikafta, Vertex’s triple therapy for cystic fibrosis, brought in $8.9 billion in sales last year. Humira, the autoimmune disease drug that Abbott Laboratories launched while Leiden was a chair there, has amassed more than $200 billion in global sales in the last two decades, making it one of the most commercially successful drugs of all time.

Now, Leiden is hoping to replicate that pattern. Vertex announced Wednesday that it would buy Alpine Immune Sciences for $4.9 billion—the largest acquisition in Vertex’s history—for a protein-based kidney disease treatment called povetacicept.

Povetacicept is a dual agonist that targets both the B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) and is currently being tested in the kidney disease IgA nephropathy. Alpine said Wednesday that in a Phase 2 trial, the drug reduced the urine protein creatinine ratio (UPCR)—a measure of how well kidneys are clearing waste—by more than 60% over 36 weeks.

Later this year, Alpine and Vertex expect to launch a Phase 3 trial—the final step before the US Food and Drug Administration would consider povetacicept for approval. But povetacicept’s real value, both Leiden and Vertex CEO Reshma Kewalramani contend, is its potential to treat multiple diseases.

“By way of its mechanism of action, dual inhibition of BAFF and APRIL, which interdict on different parts of the B-cell maturation and proliferation pathway, [povetacicept] holds the promise of a pipeline in a product for a number of B-cell-driven serious diseases,” Leiden said on an investor call Wednesday. “This reminds me very much of the potential we saw in Humira in the early days of biologics for the treatment of autoimmune diseases.”

Povetacicept has potential in membranous nephropathy, autoimmune cytopenias, lupus nephritis, and other autoimmune diseases, per Vertex’s announcement. Such an expansion would be similar to the rollout of Humira, which was initially approved for rheumatoid arthritis and later to treat psoriatic arthritis, Crohn’s disease, psoriasis, and plaque psoriasis, among other conditions.

“The breadth of indications is very comprehensive,” Kewalramani added.

Povetacicept has a few competitors already. In a research note, Leerink Partners analyst David Risinger pointed to Novartis’ zigakibart, Otsuka’s sibeprenlimab, and Vera’s atacicept, which are all designed to treat IgA nephropathy as well and are farther along in clinical development.

Vertex management is banking on the hope that povetacicept will be best in class: it targets both BAFF and APRIL, whereas zigakibart only targets APRIL, and it needs to be given once every four weeks, while atacicept is a weekly injection.

“Overall, we believe the [Alpine] acquisition is a strong strategic fit for [Vertex], who can leverage their resources and expertise in large-scale clinical development and commercial experience/infrastructure in specialty markets to maximize the value of” povetacicpet, Leerink Partners analyst Thomas J. Smith wrote in a research note. “Moreover, we believe the acquisition speaks to [Vertex’s] confidence in povetacicept’s clinical profile, translatability of biomarkers to clinical outcomes, and the commercial opportunity for this potentially best-in-class therapy, for IgAN and other B-cell mediated autoimmune diseases.”

The acquisition also serves as a homecoming for Kewalramani, a trained nephrologist who previously led Amgen’s renal division and helped found the Kidney Health Initiative. Since she took over from Leiden as CEO in 2020, Kewalramani has overseen the development of two other kidney disease drugs: inaxaplin, which is designed to block high-risk variants of the APOL1 gene, and VX-407, which is meant to treat autosomal dominant polycystic kidney disease in patients with a subset of PKD1 genetic variants. Povetacicept rounds out that portfolio, she said on the call.

“When I stand back and look at renal medicine, it’s like a renaissance in nephrology over the recent past,” Kewalramani said. “I think Vertex is leading the way with these three medicines.”