'Influx of newer agents' in gout pipeline hold promise for shifting treatment paradigm
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Although allopurinol, febuxostat and pegloticase are still relied on to do the heavy lifting in lowering urate for patients with gout, an “influx of newer agents” may help expand effective disease management, according to a presenter here.
“In the 21st century, we often think that RA is the most common condition — why? Because we have so many different medications available for RA,” Puja P. Khanna, MD, MPH, associate professor in the division of rheumatology at the University of Michigan, told attendees at the 2021 Congress of Clinical Rheumatology-East. “But guess what? Gout is actually the most common one seen in adulthood, with a prevalence of about 9.2 million U.S. adults as of 2016, according to the NHANES data.
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“What we have noticed in the last 20 years or so is that there are gaps in quality of care and shortfalls in patient education and adherence, and all-cause hospitalizations have gone up by about 410%,” she added.
Although several factors are responsible for driving the prevalence and clinical complexity of gout, one of the biggest challenges in managing the disease has been “limited new therapies,” Khanna noted. However, this began to change starting in 2006 through 2016, “when we saw an influx of newer agents.”
In this vein, Khanna called attention to several “drugs in the pipeline” for gout that have shown promising results in the past year, including verinurad (Ardea Biosciences) and arhalofenate (Kowa Pharmaceuticals), “agents that selectively target URAT-1 inhibition.”
Additionally, there is topiroxostat (Sanwa Kagaku Kenkyusho), which — “similar to febuxostat” — has been shown to reduce uric acid production by inhibiting xanthine oxidase.
“Pegadricase is also currently being studied,” Khanna told attendees, with the drug showing promise in phase 1 and phase 2 clinical trials. “It’s a similar molecule to pegloticase, in the sense that its pegylated, but it’s a pegylated version of the therapeutic enzyme uricase. It’s on a platform — the SEL-212 — which consists of SVP-rapamycin coadministered with pegadricase, so it’s a combination of a combination.”
Khanna noted that lesinurad (Zurampic, Ironwood Pharmacuticals) had been approved in 2015 at a dose of 200 mg to be combined with a xanthine oxidase inhibitor, such as allopurionol or febuxostat.
“It was not approved for the treatment of asymptomatic hyperuricemia so it could not be used as monotherapy, and neither could it be used at eGFR at less than 45 ml/min,” Khanna said.
However, in 2019, the manufacturer discontinued the marketing of lesinurad as well as their combination lesinurad/allopurinol product in the U.S. Although Ironwood Pharmaceuticals has stated this was strictly a financial decision unrelated to drug efficacy or safety, its removal has still left a gap in the gout armory.
“Even though it was a fantastic drug, it just didn’t work out,” Khanna said.
Rounding out the potential agents in development, Khanna also spotlighted new phase 2 trial data in Arthritis & Rheumatology — “fresh off the press as of last week” — comparing anakinra (Kineret, SOBI) at either 100 mg/day or 200 mg/day for 5 days with triamcinolone IV at 40 mg single dose for the treatment of gout flares.
“What was seen was that there were no difference between the two, so you could use either anakinra or triamcinolone,” Khanna said. “I use triamcinolone very rarely, but I do use anakinra a lot in my practice, simply because on the in-patient side, we can get it approved easily, and even before my fellows reach the bedside for the consult, the cardiology service has already given out anakinra and then consulted rheumatology. So, yes, you can use it, but it is not FDA-approved for the indication of acute gout quite yet.”
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Khanna PP. Optimal Treatment of Gout in 202. Presented at: Congress of Clinical Rheumatology-East annual symposium; August 12-15, 2021 (hybrid meeting).
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