With its first-in-class endothelin and angiotensin II receptor antagonist Filspari, Travere Therapeutics is providing a more efficacious treatment option for the rare autoimmune disease.
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 exacerbate pre-existing chronic infections 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. Although traditional systemic steroid therapy tends to last for years and can be lifelong, Tarpeyo is only administered for 9 months, thereby limiting the emergence of side effects as much as possible.
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.
Correction (June 7): This story has been updated from its original version to clarify that Tarpeyo can exacerbate pre-existing chronic infections, not cause new infections, and clarify that it has a limited administration period. BioSpace regrets the error.
