Vertex Pharmaceuticals has agreed to acquire Alpine Immune Sciences for approximately $4.9 billion, the companies said, in a deal designed to broaden the buyer’s specialty drug pipeline with Alpine’s Phase III-bound IgA nephropathy (IgAN) candidate.
Minutes after joining Vertex to announce the acquisition yesterday after the close of financial markets, Alpine shared positive data from its Phase I/IIa RUBY-3 trial (NCT05732402) showing that treatment with its lead candidate povetacicept (ALPN-303) resulted in urine protein to creatinine ratio (UPCR) reductions of more than 60% seen at 36 weeks—results the company said were associated with remission, resolution of hematuria, and stable renal function.
Four of the six patients (67%) achieved remission, defined as UPCR < 0.5 g/g, ≥50% reduction in UPCR from baseline, and stable renal function (≤ 25% reduction in eGFR from baseline).
As a result of its positive data, Alpine reported a successful end-of-Phase II meeting with the FDA—and plans to launch a registrational Phase III trial of 80 mg povetacicept in the second half of this year.
RUBY-3 is a multiple ascending dose, multi-cohort, open-label trial designed to assess povetacicept in autoimmune glomerulonephritis, including IgA nephropathy, for which povetacicept was administered subcutaneously (SC) once every four weeks.
As of March 1, 41 patients with IgAN had received povetacicept, either the 80 or 240 mg dose, subcutaneously every four weeks. In six patients, treatment with a subcutaneous 80 mg dose of povetacicept every four weeks resulted in a clinically meaningful improvement in proteinuria, with a 64.1% reduction from baseline in UPCR at 36 weeks (nine months), an outcome Alpine said was associated with stable renal function as assessed by estimated glomerular filtration rate (eGFR).
“Povetacicept has demonstrated potential best-in-class attributes in IgA nephropathy and has broad development potential across a number of other autoimmune and inflammatory conditions with significant unmet need,” Mitchell H. Gold, MD, Alpine’s executive chairman and CEO, said in a statement.
Outperforming competitors
Povetacicept showed roughly twice as much of a reduction in proteinuria after nine months as Vera Therapeutics’ atacicept (35–43% nine months after treatment) and more than double the reduction shown by Calliditas Therapeutics’ Tarpeyo® (budesonide; 31%), Jefferies analyst Michael J. Yee shared in a research note last night.
At 12 months, he reported, povetacicept showed 78% UPCR reduction, compared with 67% for the Novartis/Kidney Therapeutics partnered candidate zigakibart, and 62% for Otsuka Pharmaceutical’s sibiprenlimab.
“The deal makes sense to us further strengthening VRTX’s existing position in the kidney space with pot’l synergies with its existing renal portfolio,” Yee observed.
By 2026 or 2027, the Phase III trial of povetacicept is expected to generate proteinuria data—which, if positive, could be used to underpin a filing seeking accelerated approval. “This is the Phase III accelerated approval endpoint at 36 weeks w/ data around 2026–27 and should very likely be positive and is mostly de-risked, in our view,” he added.
Povetacicept is a dual antagonist of B cell activating factor (BAFF) and a proliferation inducing ligand (APRIL). Through Phase II development, Alpine said, povetacicept has shown potential best-in-class efficacy in IgAN, the most common cause of primary (idiopathic) glomerulonephritis worldwide, affecting approximately 130,000 people in the United States.
Because it is a dual BAFF/APRIL antagonist, Vertex and Alpine reason, povetacicept could benefit patients with other serious autoimmune diseases of the kidney, including membranous nephropathy and lupus nephritis, as well as autoimmune cytopenias. Clinical trials are ongoing in renal indications and autoimmune cytopenias.
There are no approved therapies for IgAN.
$3B therapy projection
“We estimate this could indeed be blockbuster at peak in the U.S. if we assume 130k x 10–15% penetration = 15–20k IgAN patients x $150–200k price = $3B pot’l in the U.S. and more including OUS [outside the U.S.],” Yee projected.
Yee added that acquiring povetacicept makes sense for Vertex since it is a complimentary drug to the company’s Phase III candidate inaxaplin (VX-147), which earlier this month advanced to the Phase III portion of the Phase II/III AMPLITUDE trial (NCT05312879) for apolipoprotein L1 (APOL1) mediated proteinuric kidney disease. Also, povetacicept would only require a small, specialized sales force, which would fall in-line with VRTX’s business development strategy.
“Alpine is a compelling strategic fit for Vertex and furthers our ambition of using scientific innovation to create transformative medicines targeting serious diseases with high unmet need in specialty markets,” stated Reshma Kewalramani, MD, FASN, Vertex’s CEO and president.
“We look forward to welcoming the talented Alpine team to Vertex and believe that together we can bring povetacicept, a potential best-in-class treatment for IgAN to patients faster,” Kewalramani added. “We also look forward to fully exploring povetacicept’s potential as a ‘pipeline-in-a-product’ and adding Alpine’s protein engineering and immunotherapy capabilities to Vertex’s toolbox.”
Alpine investors agreed with that sentiment, as the company’s shares jumped 36.5% in after-hours trading Wednesday, following a gain of nearly 21% during the trading session, rising from $38.94 to $47.04. Vertex shares dipped 1% after hours, to $393.02, after sliding 2% during the trading day from $404.48 to $397.58.
At $65 a share, the deal price is 38% above Vertex’s closing price Tuesday. The boards of Vertex and Alpine have both unanimously approved the acquisition, which is expected to close later this quarter subject to conditions that include the tender of a majority of the outstanding shares of Alpine common stock and the expiration of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act and other customary conditions.
“It became clear during our discussions with the Vertex team that we share many core values, including a commitment to patients, our employees, and an intense drive for innovation,” Gold stated. “We look forward to the opportunity, now more than ever, to make a meaningful difference in the lives of patients worldwide as part of Vertex.”
