CEO Carsten Brunn said Selecta Biosciences Inc. has “not seen a material impact” from the COVID-19 pandemic and remains on track to report in the third quarter phase IIb data from a head-to-head trial comparing its refractory gout candidate, SEL-212, with Krystexxa (pegloticase), from Horizon Therapeutics plc, of Dublin. “It’s important to note that the drugs are administered in dedicated infusion centers,” all of which “basically remain open throughout the COVID crisis,” he said.
The FDA cleared Krystexxa in September 2010 for gout in adults who don’t respond to conventional therapy or can’t tolerate it. Typically tried against the condition are drugs that lower the amount of uric acid (UA) in the blood, such as the xanthine oxidase inhibitors allopurinol and febuxostat. The former was approved as Zyloprim and the latter as Uloric, but both have since become available in generic form.
Recombinant porcine-like uricase Krystexxa is given every two weeks as an intravenous infusion. Horizon recently reported Krystexxa sales of $93.3 million, growth by 78% vs. the first quarter of 2019 and a decline of 16% vs. the fourth quarter of last year. The company, like others, cited a COVID-19-related slowdown in new patient starts, which Piper Sandler analyst David Amsellem found “intuitive, given the nature of the chronic gout population (i.e., skews older; co-morbidities are common) and the nature of the drug (i.e., intravenous infusions of an immunogenic agent where concomitant usage of immunomodulatory agents is not uncommon). Given that backdrop, it was not surprising to see management only modestly raise the higher end of its total revenue guidance range (now at between $1.40 billion and $1.45 billion, up from a range of $1.40 billion to $1.42 billion),” he wrote in a report, though Horizon’s Tepezza (teprotumumab-trbw), cleared by the FDA for thyroid eye disease in January 2020, is selling well.
Horizon said Krystexxa revenues for full-year 2020 likely will turn out similar to the $343 million seen the previous year.
The total gout population in the U.S. includes more than 8 million people, but the number of treatment-refractory patients is much smaller. Still, at least 100,000 could be candidates for treatment with a uricase enzyme product, according to estimates by Wainwright analyst Raghuram Selvaraju, and Krystexxa has captured only a few thousand of them. A prospect such as Selecta’s SEL-212 could “achieve substantially greater commercial performance,” in his view, and he put numbers to it. “Assuming annual pricing per patient in the $300,000 range – which is conservative, given Krystexxa pricing [near] $500,000 per patient annually – peak sales for SEL-212 in the U.S. alone could easily exceed $1 billion,” he wrote in a report. He projected that the drug might reach the market in 2023 and achieve peak sales of $1.6 billion in 2034, with patent protection not expiring until 2038. Selvaraju set a price target of $8 for Selecta’s stock (NASDAQ:SELB), which bears a 52-week high of $4.83 and a low of $1.28. Shares closed at $3 on May 7.
SEL-212 deploys Selecta’s Immtor technology with pegadricase, a pegylated formulation of uricase. Immtor stimulates dendritic cells so that they send tolerogenic messages to naïve T cells to develop into T regulatory cells. The drug’s strong point, in competing with Krystexxa, may lie in the latter’s tendency to generate anti-drug antibodies (ADAs). The recorded incidence of ADAs with Krystexxa has reached 90%. In the first clinical work with SEL-212, the molecule gained pleasing drops in UA, with 66% of evaluable patients in a phase IIa trial maintaining serum UA levels below 6 mg/dL, which constitutes the cutoff for efficacy in gout patients, while flares fell from 35% to a range of between 9% and 10%, with few ADAs or none. The finding seems to bode well for the phase IIb effort called Compare, due to read out later this year.
Selecta continues to work with its contract research organization and clinical sites to monitor patient follow-up in light of the COVID-19 pandemic. The Compare study is evaluating a once-monthly dose of SEL-212 compared to biweekly doses of Krystexxa, with the primary endpoint of the maintenance of serum UA levels of <6 mg/dL at three and six months. The trial completed enrollment in December 2019, and as of April 2020, half of the patients had completed the study, with all patients having reached three months of treatment.
During Selecta’s conference call with investors, Canaccord analyst John Newman said the company provided some “interesting” data at the end of 2019, showing a higher dropout rate for the active control group of patients than for the SEL-212 arm. He wanted to know if the company expects that trend to continue, since people on Krystexxa must show up to the infusion centers more often. Brunn said the less frequent dosing with SEL-212 is a key differentiator for the product with or without the COVID-19 scourge. “I don’t want to speculate about the data,” he added, which will be examined for signals related to Compare’s secondary endpoint of gout flares, such as the use of steroids. Physicians have shown a “clear trend” of avoiding the immunosuppressive agents – a concern that is “even more acute now,” given the pandemic, he noted.
Gout drug for COVID-19?
Also used against gout is tubulin binder colchicine, an oral anti-inflammatory agent that was recently added to the roster of therapies being tried in the war against COVID-19. Leaders of the experiment are implementing an unusual contactless approach and will ship the drug directly to patients’ homes within 48 hours of diagnosis, handling recruitment and follow-up visits remotely. University of California San Francisco and the New York University School of Medicine will serve as the first two U.S. sites for the phase III study called Colcorona, led by the Montreal Heart Institute. The study also has locations in Canada. More are being developed in Europe. Research published at the end of 2019 in The New England Journal of Medicine found that low doses of the drug safely reduced the risk of recurrent cardiac events, particularly in people who have already survived a heart attack. The randomized double-blind placebo-controlled trial aims to enroll 6,000 newly diagnosed patients over age 40 and with at least one risk factor for serious COVID-19 complications, such as chronic pulmonary disease, heart disease or age greater than 70 years. Thirty days after enrollment, the study will assess whether colchicine treatment reduces rates of hospitalization or death.
New York-based Olatec Therapeutics LLC is developing dapansutrile in gout flares, which was proved safe and effective in knocking down joint pain in a phase IIa experiment. The compound inhibits the NLRP3 inflammasome and activation of interleukin-1 beta. In a study that was published online in The Lancet Rheumatology, 144 outpatients were evaluated at a clinic in the Netherlands. Of those, 34 were enrolled and 29 were included in the per-protocol population. Researchers concluded that results from the trial – funded by Olatec, the NIH and the Interleukin Foundation – are encouraging but said dapansutrile needs further exploration.