Vertex Pharmaceuticals to Acquire Alpine Immune Sciences for $4.9 Billion to Advance Povetacicept in IgA Nephropathy and Autoimmune Diseases

On April 10, according to a press release issued by Vertex Pharmaceuticals (hereinafter referred to as “Vertex”), Vertex and Alpine Immune Sciences (hereinafter referred to as “Alpine”) have entered into an acquisition agreement.

Vertex to Acquire Alpine for $65 per Share, Totaling Approximately $4.9 Billion (RMB 35.454 Billion), to Expand Its Portfolio in Kidney and Immune System Diseases. Alpine’s stock closed at $37.57 on Tuesday, representing a premium of nearly 80% for this transaction. The deal has been approved by the boards of directors of both companies and is expected to close later this quarter.

Alpine’s core pipeline features its lead molecule, povetacicept (ALPN-303), a potent dual antagonist of B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL). Povetacicept has demonstrated potential best-in-class efficacy in IgA nephropathy (IgAN), with Phase III clinical trials expected to commence in the second half of this year.

IgA nephropathy, also known as Berger's disease, is a primary glomerular disease characterized by recurrent episodes of gross or microscopic hematuria, mesangial cell proliferation, increased matrix, and widespread IgA deposition.

IgA Nephropathy is the most common primary glomerular disease worldwide and one of the leading causes of chronic kidney disease (CKD) and kidney failure. It predominantly affects young adults, with 30% of cases occurring between the ages of 20 and 39. The disease typically follows a chronic progressive course, with 20%–40% of patients gradually progressing to end-stage renal disease (ESRD) within 10 to 20 years.

According to Frost & Sullivan’s estimates, the global number of IgA nephropathy patients will reach nearly 10 million in 2025, including 2.3 million patients in China. The global market for IgA nephropathy therapeutics is projected to grow from USD 567 million in 2020 to USD 1.196 billion (RMB 8.654 billion) in 2025, representing a compound annual growth rate (CAGR) of 16.1%. Meanwhile, China’s market for IgA nephropathy therapeutics is expected to increase from USD 37 million in 2020 to USD 109 million in 2025, with a CAGR of 24.6%.

However, there is currently no cure for IgA nephropathy, and medications can only slow the progression of the disease. Most pharmacological treatments for IgA nephropathy are currently used off-label.

Only two drugs have been approved globally for IgA nephropathy: Everest Medicines’ and Calliditas Therapeutics’ budesonide delayed-release capsules (Nefecon).^®) and Travere Therapeutics’ sparsentan tablets (TRAVERE).

In November 2023, the National Medical Products Administration approved Nefecon (budesonide delayed-release capsules), a product developed in collaboration between Everest Medicines and Calliditas^®) granted conditional marketing authorization in China for the treatment of adult patients with primary IgA nephropathy at risk of progression.

This drug is the world’s first disease-modifying therapy for IgA nephropathy. It was first approved in the United States on December 15, 2021 (brand name: TARPEYO) and in the European Union on July 15, 2022 (brand name: Kinpeygo). It is the first innovative drug approved by three major regulatory authorities—the U.S. FDA, the European EMA, and China’s NMPA—for the treatment of IgA nephropathy, and also the first non-oncology drug included in the Breakthrough Therapy Designation program by China’s National Medical Products Administration (NMPA).

In contrast, Alpine’s lead molecule, Povetacicept (ALPN-303), is a potent dual antagonist of B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL). BAFF binds to three receptors: the BAFF receptor (BAFF-R), B-cell maturation antigen (BCMA), and transmembrane activator and CAML interactor (TACI), whereas APRIL exerts its effects by binding to BCMA and TACI. Both cytokines play important roles in the study of autoimmune diseases.

Povetacicept is a mutant TACI-Fc fusion protein, belonging to the same class of drugs as atacicept and telitacicept. Compared with these agents, povetacicept exhibits higher affinity for APRIL and BAFF, holding promise to become the best-in-class TACI-Fc. In Phase II clinical data, povetacicept has indeed demonstrated potential best-in-class efficacy in IgA nephropathy (IgAN).

Furthermore, the indications for Povetacicept also include immune-mediated diseases such as systemic lupus erythematosus, membranous nephropathy, and cytopenias. Currently, the most advanced indication for Povetacicept is IgA nephropathy, with Phase III clinical trials expected to commence in the second half of this year. Once Povetacicept secures initial approval, Vertex will gain entry into a vast kidney disease market with significant unmet medical needs.

In addition to acquiring Alpine and securing the core asset povetacicept, thereby establishing a presence in the IgA nephropathy field, Vertex has also been actively advancing its pipeline for other autoimmune diseases (such as rheumatoid arthritis, cancer, and inflammatory bowel disease) in recent years. Notable examples include the highly anticipated stem cell therapy VX-880 and the VX-264 program (indicated for type 1 diabetes).

Furthermore, Vertex has a clinical pipeline for other serious diseases, encompassing small molecules, cell therapies, and gene therapies. The therapeutic areas include cystic fibrosis (CF), sickle cell disease, beta-thalassemia, APOL1-mediated kidney disease, pain, and alpha-1 antitrypsin deficiency. Among these, the CF pipeline is the most advanced in terms of development progress.

As a leading enterprise in the field of cystic fibrosis (CF) therapeutics, Vertex currently has four CF drugs on the market, all targeting CFTR, the key protein involved in the pathogenesis of CF. There are also several clinical and research projects ongoing in its pipeline. The marketed drugs include Kalydeco, Orkambi, Symdeko, and Trikafta, with the first three capable of treating approximately 40,000 patients worldwide. Currently, Vertex faces almost no competition in the CF drug sector and enjoys high profit margins.

Vertex has amassed tens of billions of dollars in wealth through its drug portfolio in the cystic fibrosis (CF) field, and at its peak, it identified autoimmune diseases as the next key strategic focus. In fact, Vertex is not alone among pharmaceutical giants with a market capitalization exceeding $100 billion in viewing the autoimmune disease sector favorably; in recent years, major pharmaceutical companies such as AbbVie, Johnson & Johnson, Roche, Sanofi, and Novartis have also been strategically prioritizing this area. Notably, AbbVie has retained the title of “King of Drugs” for 11 consecutive years, driven by its blockbuster drug Humira.

According to Frost & Sullivan’s projections, the global market for autoimmune disease drugs is expected to reach $176 billion by 2030, with a compound annual growth rate (CAGR) of 3.6% from 2022 to 2030. Among this, China’s market size is projected to approach $25 billion by 2030, representing a tenfold increase compared to 2020, making it a significant source of incremental growth in the global autoimmune drug market.

Recognizing this blue-ocean opportunity, Chinese enterprises have expanded rapidly in recent years. According to statistics from R&D Ke, among the nearly 80 “active players” in new drug development listed on the A-share and H-share markets, 43 companies have entered the autoimmune disease arena. In particular, in therapeutic areas such as atopic dermatitis, psoriasis, rheumatoid arthritis, and systemic lupus erythematosus, some domestic pharmaceutical companies have achieved preliminary R&D successes. In the field of psoriasis, several drug candidates have advanced to Phase III clinical trials or filed for marketing approval; leading companies in terms of R&D progress include Jiangsu Hengrui Medicine, Akeso, Quanxin Biotech, and 3SBio.

Blockbuster Drugs Emerge from the Autoimmune Space. Who Will Claim the Next Blockbuster Title? Will a Chinese Pharmaceutical Company Be Among Them? Let Time Provide the Answer.

Reference: “What Does the Approval of the World’s First Disease-Modifying Therapy for IgA Nephropathy in China Mean?”