Freiberg's Disease

Travere Therapeutics has won FDA approval for a drug that treats a rare autoimmune disorder that is typically first noticed as blood in the urine and can progress over time to end-stage kidney failure. The regulatory decision for Travere’s drug covers makes it the second FDA-approved therapy for adults with immunoglobulin A nephropathy (IgAN), a condition that stems from the buildup of the disease’s namesake antibodies in the kidney, leading to organ damage. The Travere drug, known in development as sparsentan, will be commercialized under the name “Filspari.” IgAN, also known as Berger’s disease, affects an estimated 150,000 people in the U.S., according to San Diego-based Travere. The accelerated approval for Filspari announced last Friday comes about 14 months after the accelerated nod for Calliditas Therapeutics’ Tarpeyo. But Calliditas’s drug is a steroid whose immunosuppressive effect can lead to side effects throughout the body. A growing field of companies is pursuing IgAN medicines that offer therapeutic benefit without causing systemic effects. Travere is claiming the mantle for the first IgAN therapy that does not suppress the immune system. Filspari, a small molecule formulated as a once-daily pill, is designed to selectively block two pathways associated with IgAN progression. The FDA approval specifically covers adults at risk of rapid disease progression, which Travere estimates is between 30,000 and 50,000 patients. The FDA decision for Filspari was based on preliminary Phase 3 data showing a reduction in levels of certain proteins in the urine following treatment. That’s the same basis used for the accelerated approval of Calliditas’s drug in 2021. The speedy FDA nods for both drugs noted that clinical testing has not yet established whether treatment slows kidney function decline in IgAN patients. The urine protein measure for Filspari happened at 36 weeks. The Phase 3 test of Filspari is ongoing, and those results could be used to confirm the drug’s clinical benefit. Additional study goals include assessing estimated glomerular filtration rate (eGFR), a measure of kidney function, after two years of treatment. Travere expect preliminary eGFR data in the fourth quarter of this year. Those results could support full regulatory approval for the drug. The most common side effects reported in the study included swelling in the legs, low blood pressure, dizziness, elevated potassium levels in the blood, and anemia. Filspari’s label carries a black box warning that cautions physicians and patients about risks such as elevated liver enzymes, liver toxicity, and liver failure. According to the prescribing information, patients must be monitored for liver problems monthly for the first 12 months of treatment, and then every three months afterward. The drug is available only under a Risk Evaluation and Mitigation Strategies (REMS) program, which requires the company to come up with a strategy that specifically spells out how it will manage the product’s risks. In a note sent to investors on Tuesday, William Blair analyst Tim Lugo wrote that the patient-monitoring requirement was expected after Travere announced last fall that the FDA asked the company to add liver monitoring to the REMS. He added that a modest increase in adverse effects is expected, and the higher incidence of such problems in the clinical trials do not raise any major concerns. Travere set a $9,900 price for a 30-day supply of Filspari, which is a discount to the $14,160 price that Calliditas set for Tarpeyo following that drug’s approval. In an investor presentation, Travere said it believes the data for Filspari so far support making that drug the new treatment standard in IgAN. Sparsentan is also in late-stage clinical development for focal segmental glomerulosclerosis (FSGS), a different rare kidney disorder. Travere expects preliminary data will become available in the second quarter of this year, followed by a supplemental new drug application in FSGS submitted to the FDA in the second half of the year. Lugo said in the research note that the Travere drug has the potential to achieve blockbuster status in both indications. “Although eGFR data in FSGS was insufficient for an accelerated submission, we believe that the positive interim readouts from the PROTECT study in IgAN, as well as the positive interim analysis from the DUPLEX study in FSGS, provide mechanistic validation,” Lugo said. “We continue to believe that Filspari in both FSGS and IgAN represent blockbuster opportunities for the company.”

The FDA approved Travere Therapeutics’ treatment for a rare kidney disease on Friday, notching a win for the company after the review of the drug was delayed by three months last year. The accelerated approval for sparsentan means Travere can now deliver the drug, which will be sold as Filspari, to patients with IgA nephropathy. In IgAN, or Berger’s disease, immunoglobulin builds up and disrupts the waste filtration process in the kidneys, which can lead to blood and protein in urine. The approval comes with a warning about liver and fetal toxicity, and the company will have to run a risk evaluation and mitigation strategy, or REMS, as part of the approval. It will require doctors to go through special training, and patients to be enrolled in a monitoring program, in order for the drug to be prescribed. The company plans to charge $9,900 for a 30-day supply, or about $120,000 a year. Travere estimates that there are 30,000 to 50,000 patients who could get the drug as of its launch. The FDA’s original Nov. 17 decision date was pushed back after the agency asked Travere to update its REMS, typically meant to monitor drugs that carry more significant potential for side effects. CEO Eric Dube previously said on a conference call the update to liver monitoring was “consistent with some of the other products in the endothelin receptor antagonist class.” A confirmatory study of the drug is ongoing, with topline results expected in the fourth quarter to support a request for traditional approval, the company has said. Travere is scheduled to report full-year 2022 results next week. SVB Securities analysts have said that a REMS program for liver monitoring would “undoubtedly be an added burden for physicians and patients,” but that they thought it could be removed with more clinical data. They cited the example of other endothelin receptor antagonists such as Gilead’s Letairis, which is used to treat pulmonary arterial hypertension. Other biotechs are also attempting to treat IgAN. Calliditas Therapeutics won accelerated approval for the delayed-release version of an old steroid for the reduction of proteinuria (protein in the urine) in primary IgAN back in December 2021. Seattle-based Chinook Therapeutics anticipates requesting an accelerated approval for its drug in the third quarter, Novartis expects a Phase III readout in the indication this year and Vera Therapeutics is headed toward late-stage studies. Travere has tried twice to get accelerated approval of sparsentan in another indication, focal segmental glomerulosclerosis (FSGS), in which scarring forms on the kidneys. Topline results from two-year confirmatory endpoints will come out next quarter for that indication, Travere previously said , noting a supplemental NDA would be filed in the second half of this year, depending on the results. The San Diego biotech rebranded in fall 2020 to rid itself of ties to the legacy name of Retrophin, the company founded by “Pharma Bro” Martin Shkreli in 2011. Travere’s moniker stems from Latin roots of the words “path” (tractus) and “truth” (ver). Editor’s note: This story has been updated to include the cost of the drug.

A quiet biotech is reporting some positive data in a rare fibrotic disease. Certa Therapeutics — based in Melbourne, Australia — reported Monday that a Phase II trial showed “significant improvements across multiple efficacy measures” in patients with scleroderma, such as a systemic sclerosis index and skin scores. The main goal of the study, per Certa, was to examine the pharmacokinetics, pharmacodynamic effects and safety of FT011 in patients with scleroderma, a rare autoimmune disease that can cause inflammation in the skin and other parts of the body, like the lungs. Also known as crest syndrome, it has been associated with chronic hardening and tightness of the skin. But Certa also tracked a number of efficacy measures to see if the drug works. The trial recruited 30 adults that were randomly assigned to either a placebo group or one of two dose groups: 200mg or 400mg orally daily for 12 weeks. After those 12 weeks, Certa saw “clinically meaningful improvement in 60 percent of patients” treated with the 400mg dose of the therapy in a Phase II study, adding that it saw a p-value of p=0.019 versus placebo. Investigators also looked at a metric called a CRISS score, which predicts a patient’s chances from 0 to 1 of improvement based on five variables, including skin thickness and lung function. Three patients who were on FT011 achieved the maximum CRISS score of 1, Certa added. The biotech is running an open-label extension study for an additional nine months after the initial 12-week study. CEO Darren Kelly said in a statement that the readout “paves the way for a confirmatory global Phase III study.” A query to the Australian biotech was not immediately returned to Endpoints News . FT011 was originally developed by a company called Fibrotech, which had taken the drug through a Phase Ia study in diabetic neuropathy. Shire then acquired Fibrotech in 2014 when it bought the company for $75 million plus up to $600 million milestones — before Takeda bought out Shire in 2019. Certa, led by several former Fibrotech execs, including ex-CEO Kelly, then picked up the drug and was able to start a Phase II trial in 2021. Certa is not the only biotech that has been working on the rare disease. Cell and gene therapy biotech Castle Creek Biosciences has been working on FCX-013, a gene therapy for moderate and severe forms of scleroderma. Boehringer Ingelheim’s Ofev is also approved for interstitial lung disease associated with systemic sclerosis or scleroderma.