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On October 22, 2024, Otsuka Pharmaceutical announced positive top-line interim data from the phase III clinical trial of sibeprenlimab for treating adults with Immunoglobulin A nephropathy (IgA nephropathy).  This multi-center, randomized, double-blind, placebo-controlled trial is the largest of its kind, involving approximately 530 adult patients with IgA nephropathy. The study aims to evaluate the efficacy and safety of a 400 mg subcutaneous injection of sibeprenlimab every four weeks compared to a placebo. After nine months of treatment, patients receiving sibeprenlimab showed a statistically and clinically significant reduction in the 24-hour urine protein/creatinine ratio (UPCR). The safety profile of the drug was consistent with previously reported data. The company plans to review the interim results with the FDA to potentially expedite regulatory approval. The study is ongoing, with final results expected to be released in early 2026. About SibeprenlimabSibeprenlimab (VIS649) is an anti-proliferation-inducing ligand (APRIL) antibody that works by binding and neutralizing APRIL, thereby reducing the levels of IgA and pathogenic galactose-deficient IgA1 (Gd-IgA1). By decreasing Gd-IgA1 production, sibeprenlimab may help slow renal damage and progression to end-stage kidney disease (ESKD).  Initially developed by Visterra, Otsuka Pharmaceutical acquired Visterra in 2018 for approximately $430 million, obtaining sibeprenlimab along with several other investigational products for IgA nephropathy and other kidney-related conditions. The complete results of the drug’s phase II clinical trial were published in the New England Journal of Medicine (NEJM) and presented at the 2023 American Society of Nephrology (ASN) conference. The findings demonstrated: ·a significant reduction in proteinuria in IgA nephropathy patients treated with sibeprenlimab for 12 months compared to placebo. ·At month 12, the geometric mean ratio reduction in 24-hour UPCR from baseline was 47.2%, 58.8%, 62.0%, and 20.0% in the sibeprenlimab groups receiving 2, 4, and 8 mg/kg doses, and the placebo group, respectively. ·The annualized change in estimated glomerular filtration rate (eGFR) for the sibeprenlimab groups and the placebo group was -2.7, +0.2, -1.5, and -7.4 ml/min/1.73m², respectively, indicating stabilization of eGFR with sibeprenlimab use.  ·The incidence of treatment-emergent adverse events (TEAEs) was similar to the placebo, with no adverse toxicity or clinically significant evidence of immunosuppression observed through month 16 follow-up. About APRIL DrugsAPRIL is a cytokine in the tumor necrosis factor (TNF) family that promotes B cell survival and class switching, leading to the production of IgA, particularly Gd-IgA1. This IgA1 forms immune complexes in the kidneys.  In patients with IgA nephropathy (IgAN), APRIL stimulates lymphocytes to produce more pathogenic IgA. If this process can be blocked, theoretically, it could prevent IgA nephropathy at its source. According to incomplete statistics, there are currently about a dozen drugs in development targeting APRIL, but none have been approved for market release. About IgA NephropathyImmunoglobulin A nephropathy (IgAN) is a type of glomerulonephritis caused by immune complexes, commonly presenting with hematuria, proteinuria, and progressive renal failure. Although IgAN is considered a rare disease, it is the most common cause of primary kidney disease worldwide. It is associated with renal inflammation, hematuria, and proteinuria. Patients may eventually progress to renal failure or end-stage renal disease (ESRD), with up to 50% requiring dialysis or kidney transplantation over the disease course. The number of IgAN patients globally and in China is expected to remain relatively stable. According to a Frost & Sullivan report, the global number of IgAN patients increased from 8.8764 million in 2016 to 9.2669 million in 2020 (including 2.2 million in China). It is projected that the global IgAN patient population will reach 9.7306 million by 2025 (including 2.3 million in China) and 10.1652 million by 2030 (including 2.37 million in China). According to IQVIA's estimates, the global market for IgA nephropathy treatments is expected to grow from $567 million in 2020 to $1.196 billion by 2025, with a compound annual growth rate (CAGR) of 16.1%. By 2030, the global market size for IgA nephropathy treatments could reach several billion dollars or even higher.  Current treatment strategies for IgAN mainly focus on supportive care and symptom relief. Supportive treatment primarily involves the use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) to control blood pressure and reduce urinary protein excretion, along with glucocorticoids and immunosuppressants for long-term management. These treatments may have significant side effects and limited clinical efficacy. ·Iptacopan (trade name: Fabhalta) received accelerated approval from the FDA in August 2024 for reducing proteinuria in adult patients with IgA nephropathy. Iptacopan is an oral, potent, selective, small molecule FB inhibitor that acts upstream of the terminal pathway of the complement system C5. It may offer treatment for diseases caused by alternative pathway dysregulation while not compromising other complement pathway-mediated immune responses against microbial invasion, thus reducing infection risk for patients. ·Nefecon is a delayed-release formulation of budesonide and the first approved drug by both the FDA and EMA for treating IgAN. It works by releasing budesonide at the ileal Peyer's patches. The drug was approved in China in November 2023, with Everest Medicines holding development rights in Greater China. ·Sparsentan is a dual endothelin angiotensin receptor antagonist (DEARA) targeting and blocking endothelin A receptor and angiotensin II subtype 1 receptor pathways. It protects glomerular podocytes, prevents glomerulosclerosis and mesangial cell proliferation, and reduces proteinuria. It is the first approved non-immunosuppressive therapy for IgA nephropathy. How to obtain the latest research advancements in the field of biopharmaceuticals? 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Grand Warszawski/Shutterstock Swiss pharma giant Roche is pushing deeper into the immunoglobulin A nephropathy (IgAN) space. The company is licensing an investigational antisense medicine from longtime partner Ionis Pharmaceuticals and plans to drive it into Phase III studies. The experimental drug in question is IONIS-FB-L Rx, which hit the mark in a Phase II study showing a change in urinary protein after 29 weeks of treatment. Full data from this mid-stage study has been submitted for presentation at upcoming medical conferences. In 2018, Roche and Ionis inked a $700 million deal to evaluate IONIS-FB-L Rx as a potential medication designed to slow or stop the progression of geographic atrophy due to age-related macular degeneration. For this indication, the therapeutic is being assessed in the Phase II GOLDEN trial. IONIS-FB-L Rx is an antisense drug that uses Ionis’ LIgand Conjugated Antisense (LICA) technology. It is designed to reduce the production of FB, a key protein in the complement innate immune system. FB is predominately produced in the liver and circulates throughout the vascular system, including vessels in the eye and kidney. IgA nephropathy, also known as Berger’s disease, is a rare kidney disease that can lead to renal failure. Berger’s disease occurs when the deposits of the antibody IgA build up in the kidneys, causing inflammation that can lead to damage to the organs. The deposits can cause the kidneys to leak blood and protein into the urine. IgA nephropathy complications can include high blood pressure and chronic kidney disease, which can sometimes progress to kidney failure. A Hotly Contested Space Last year, Calliditas Therapeutics scored its inaugural regulatory approval in the United States for Tarpeyo, the first drug to decrease urine protein in IgA nephropathy. Roche intends to take the Ionis-developed asset and advance it through late-stage studies and potential commercialization. IgAN is a hotly-contested area with multiple companies hoping to carve out a niche. Last month, Alnylam announced plans to take cemdisiran, an RNAi mono-therapeutic into a Phase III trial for this indication. The decision followed positive topline results from a Phase II trial that showed patients who received cemdisiran had a 37% reduction in urine protein to creatinine ratio compared to placebo. Chinook Therapeutics is also developing an asset for IgAN, but its experimental drug BION-1301 is not as far along as either Roche or Alnylam. BION-1301, an anti-APRIL monoclonal antibody, is being studied in a Phase I/II trial. In May, Seattle-based Chinook presented updated data from the study that showed BION-1301 demonstrated an approximate 50% reduction in urine protein after three to six months of treatment. Additionally, the company noted those reductions improved over time, with a reduction of about 70% at one year and beyond in several patients. In its announcement, Ionis did not specify when Roche might begin its Phase III trial of IONIS-FB-L in IgAN. “Roche's decision to advance the program reaffirms our shared confidence in the ability of Ionis' antisense medicines to effectively target the root cause of difficult to treat diseases like immunoglobulin A nephropathy," Michael McCaleb, vice president of clinical development at Ionis said in a statement. "The results of the Phase II study provide initial clinical evidence that IONIS-FB-L Rx reduces complement and protein levels in the urine of patients with IgAN.” Under terms of the deal, Ionis will receive $55 million from Roche for the licensing fee, as well as for achieving a development milestone in the GOLDEN study.

Grand Warszawski / Shutterstock The experimental drug, being developed to treat immunoglobulin A nephropathy, is IONIS-FB-L Rx, which hit the mark in a Phase II study showing a change in urinary protein after 29 weeks of treatment. Grand Warszawski/Shutterstock Swiss pharma giant Roche is pushing deeper into the immunoglobulin A nephropathy (IgAN) space. The company is licensing an investigational antisense medicine from longtime partner Ionis Pharmaceuticals and plans to drive it into Phase III studies. The experimental drug in question is IONIS-FB-L Rx, which hit the mark in a Phase II study showing a change in urinary protein after 29 weeks of treatment. Full data from this mid-stage study has been submitted for presentation at upcoming medical conferences. In 2018, Roche and Ionis inked a $700 million deal to evaluate IONIS-FB-L Rx as a potential medication designed to slow or stop the progression of geographic atrophy due to age-related macular degeneration. For this indication, the therapeutic is being assessed in the Phase II GOLDEN trial. IONIS-FB-L Rx is an antisense drug that uses Ionis’ LIgand Conjugated Antisense (LICA) technology. It is designed to reduce the production of FB, a key protein in the complement innate immune system. FB is predominately produced in the liver and circulates throughout the vascular system, including vessels in the eye and kidney. IgA nephropathy, also known as Berger’s disease, is a rare kidney disease that can lead to renal failure. Berger’s disease occurs when the deposits of the antibody IgA build up in the kidneys, causing inflammation that can lead to damage to the organs. The deposits can cause the kidneys to leak blood and protein into the urine. IgA nephropathy complications can include high blood pressure and chronic kidney disease, which can sometimes progress to kidney failure. A Hotly Contested Space Last year, Calliditas Therapeutics scored its inaugural regulatory approval in the United States for Tarpeyo, the first drug to decrease urine protein in IgA nephropathy. Roche intends to take the Ionis-developed asset and advance it through late-stage studies and potential commercialization. IgAN is a hotly-contested area with multiple companies hoping to carve out a niche. Last month, Alnylam announced plans to take cemdisiran, an RNAi mono-therapeutic into a Phase III trial for this indication. The decision followed positive topline results from a Phase II trial that showed patients who received cemdisiran had a 37% reduction in urine protein to creatinine ratio compared to placebo. Chinook Therapeutics is also developing an asset for IgAN , but its experimental drug BION-1301 is not as far along as either Roche or Alnylam. BION-1301, an anti-APRIL monoclonal antibody, is being studied in a Phase I/II trial. In May, Seattle-based Chinook presented updated data from the study that showed BION-1301 demonstrated an approximate 50% reduction in urine protein after three to six months of treatment. Additionally, the company noted those reductions improved over time, with a reduction of about 70% at one year and beyond in several patients. In its announcement, Ionis did not specify when Roche might begin its Phase III trial of IONIS-FB-L in IgAN. “Roche’s decision to advance the program reaffirms our shared confidence in the ability of Ionis’ antisense medicines to effectively target the root cause of difficult to treat diseases like immunoglobulin A nephropathy,” Michael McCaleb, vice president of clinical development at Ionis said in a statement. “The results of the Phase II study provide initial clinical evidence that IONIS-FB-L Rx reduces complement and protein levels in the urine of patients with IgAN.” Under terms of the deal, Ionis will receive $55 million from Roche for the licensing fee, as well as for achieving a development milestone in the GOLDEN study.