Budesonide

This official launch marks a significant advancement in patient care in mainland China, introducing a new era in the treatment of IgA nephropathy ​ (IgAN). IgA nephropathy (IgAN) is a common chronic kidney disease which mainly affects young adults. In IgAN a protein called immunoglobulin A (IgA) becomes trapped in the very fine filters of the kidney (glomeruli), causing damage and scarring to the whole kidney. China has the highest prevalence of primary glomerular diseases globally, with IgAN accounting for about 35% to 50% of cases. Most IgAN patients risk progressing to end-stage renal disease during their lifetime, often requiring dialysis or kidney transplantation. Current treatments, like renin-angiotensin system (RAS) inhibitors, fail to address the underlying disease progression, highlighting a significant unmet medical need. Rogers Yongqing Luo, chief executive officer of Everest Medicines, said the commercialization of Nefecon in the Chinese market represents a significant milestone for Everest and a breakthrough for IgAN patients in China. Nefecon has undergone a 20-year research and development process, becoming the first non-oncology therapeutic to receive Breakthrough Therapy Designation in China by the China National Medical Products Administration (NMPA), and the first treatment for IgAN to receive full approval from the US Food and Drug Administration (FDA). Five million IgAN patients in China He said: “It is also the first approved medicine with an IgAN indication by the NMPA in China. On behalf of the company, I would like to extend my gratitude to all parties who have assisted in obtaining the approval for Nefecon’s market entry and clinical use in mainland China, especially the clinical investigators and the 62 Chinese patients who participated in the global phase 3 clinical trials. With approximately 5 million IgAN patients in China and over 100,000 newly diagnosed patients annually, there is a significant unmet clinical demand. googletag.cmd.push(function () { googletag.display('text-ad1'); }); Professor Zhang Hong is from Peking University First Hospital, a member of the global steering committee for the phase 3 clinical study NefIgArd. He said: “We will actively engage with all stakeholders to improve the accessibility and affordability of this innovative therapy for IgAN. Moreover, we will contribute to improving nephropathy diagnosis, treatment, and disease management, ultimately benefiting more patients. As we advance the commercialization of Nefecon in China and Asia, we will also actively promote the development of other innovative drugs in the nephropathy field, extending benefits to more patients.” “IgAN is the most common primary glomerular disease, occurring at a young age with a high possibility of progressing to end-stage renal disease. Compared to European and American populations, Chinese IgAN patients experience faster disease progression and poorer prognosis, imposing a heavy burden on patients and society. The full results of the NefIgArd study demonstrate that Nefecon can protect renal function, delay progression to dialysis or kidney transplantation, and significantly reduce urinary protein and hematuria. It is also safe and well-tolerated.” “Data analysis of the Chinese population shows that Nefecon reduces kidney function decline by 66%, and delays disease progression to dialysis or kidney transplantation by 12.8 years. The approval of Nefecon fills the gap in targeted therapy for IgAN in China, benefiting Chinese patients, improving disease prognosis, and providing clinicians with new treatment options.” Nefecon - even greater benefit in delaying kidney function decline The company says the latest analysis, presented at the World Congress of Nephrology 2024, provides further evidence that Nefecon may offer even greater benefit in delaying kidney function decline in Chinese patients with more rapidly progressing disease, without compromising patients' quality of life. Positive results from the global Open Label Extension (OLE) study based on the NefIgArd phase 3 study validated the efficacy and safety of re-treatment with Nefecon independent of prior treatment cycles, providing a solid scientific basis for future long-term maintenance regimens of Nefecon. "IgAN is highly prevalent in Asia and is one of the main causes of kidney failure in young adults in China. Among IgAN patients, the risk of progressing to end-stage renal disease in Asian populations is 56% higher compared to other populations, and the disease progresses more rapidly, imposing a significant medical burden on patients, families, and society. Therefore, more proactive treatment is needed to intervene and control the risk of disease progression, delaying the need for dialysis or kidney transplantation. “For a long time, this disease has lacked targeted treatment options, resulting in significant unmet clinical needs," said Professor Xie Jingyuan, chief physician of the Department of Nephrology, Ruijin Hospital affiliated with Shanghai Jiao Tong University School of Medicine. “Nefecon, as the world's first-in-disease therapy for IgAN, has treated over one hundred patients in total through its early-access program in Boao last April. During the follow-up period, Nefecon was found to be effective in stabilizing renal function, reducing proteinuria and hematuria, and was well tolerated by the patients. It is of great significance for Nefecon to be officially commercialized in mainland China, helping patients with IgAN to initiate treatment as early as possible.” Nefecon received approval from the China NMPA in November 2023 for the treatment of primary IgAN in adults at risk of disease progression. Additionally, Nefecon has been approved in multiple countries and territories across Europe, the US, and Asia.

Pictured: A kidney with IgA antibodies/Taylor Tieden for BioSpace Despite having not yet received full approval, Travere Therapeutics’ first-in-class endothelin and angiotensin II receptor antagonist Filspari—which received the FDA's accelerated approval in February 2023—is already making strides in treating IgA nephropathy. A rare autoimmune disease, IgA nephropathy occurs when immunoglobulin A accumulates in the kidneys, leading to blood and protein in the urine. It affects around 60,000 people in the U.S. According to the National Kidney Foundation, the four main classes of approved drugs used to treat IgA nephropathy are corticosteroids, immunotherapies, ACE inhibitors and angiotensin II blockers. While corticosteroids and immunotherapies tamp down immune responses, ACE inhibitors decrease angiotensin production by inhibiting angiotensin-converting enzymes, and angiotensin II blockers inhibit the angiotensin II receptor. By decreasing overall angiotensin activity and its downstream effects in the body, ACE inhibitors and angiotensin II blockers reduce hypertension and proteinuria over time via the renin-angiotensin-aldosterone system. There is ample reason to believe that Filspari is clinically efficacious enough to warrant serious provider consideration compared to traditional treatments. For example, immunotherapies indicated for treating IgA nephropathy, such as cyclophosphamide combined with prednisone, lead to adverse effects ranging from drug-induced hepatitis to widespread systemic infections. When Filspari was approved last year, it was touted as the first and only non-immunosuppressive therapy to reduce proteinuria in IgA nephropathy. The adverse effects caused by immunotherapies are riskier to manage than are Filspari’s adverse effects, which include peripheral edema, hypotension, dizziness, hyperkalemia and anemia. According to Travere, while traditional ACE inhibitors or angiotensin receptor blockers with no endothelin activity have been used to treat IgA nephropathy, these agents have only been able to delay end stage renal disease by 7.9 years on average when initiated in patients with an estimated glomerular filtration rate that indicates kidney disease. Meanwhile, angiotensin II receptor antagonists with endothelin inhibition, such as irbesartan or Filspari, can delay end-stage renal disease for longer—by 11.1 years on average for irbesartan and 15.6 years for Filspari. (Irbesartan, brand name Avapro, is a drug chemically similar to Filspari that is approved to treat hypertension and diabetic nephropathy.) Because the standard of care treatment with traditional ACE inhibitors or angiotensin receptor blockers with endothelin activity provides more effective long-term management of IgA nephropathy than angiotensin II receptor antagonists without endothelin inhibition, drugs with endothelin-inhibiting activity will be favored. In terms of newer medications on the market, although Calliditas Therapeutics’ systemic steroid Tarpeyo (budesonide) received full approval in December 2023 for IgA nephropathy, it can cause infections if used chronically and does not address the root cause of IgA nephropathy but rather targets the source of IgA antibody production before the IgA autoantibodies end up in the kidney. In addition to seeking indication expansions in other renal diseases, such as focal segmental glomerulosclerosis, Travere aims to make Filspari the first-line agent for IgA nephropathy and to push for its use in earlier interventions to maximize nephroprotection. Because Filspari can be combined with Tarpeyo but not with other angiotensin receptor blockers, future clinical trials may involve examining this combination for IgA nephropathy. With Filspari, Travere is well-positioned to continue expanding its rare disease footprint in the coming years. Jia Jie Chen writes analyses focusing on drug development in the biotech and pharma industries for BioSpace. He has a doctorate degree in pharmacy and experiences ranging from biotech equity research to business intelligence analysis. Follow him on LinkedIn.