Selecta Biosciences and Sobi have laid down a marker in their attempt to challenge Horizon for the gout market, delivering phase 3 data that suggest their SEL-212 candidate can match the efficacy of Krystexxa despite being administered less frequently.
The Selecta drug candidate, which Sobi licensed for $100 million upfront in 2020, is a formulation of the immunogenic enzyme pegadricase and ImmTOR. Administering ImmTOR, biodegradable nanoparticles encapsulating the immunomodulator rapamycin, is designed to cut the immune response to pegadricase and prevent the development of antidrug antibodies that would render the enzyme ineffective.
Krystexxa comes at the problem from a different angle, coupling the uricase enzyme to polyethylene glycol to create a pegylated molecule with reduced immunogenicity. Sales of Krystexxa grew 27% last year to hit a new high of $716.2 million.
Selecta and Sobi want a piece of the action. To muscle in on the market, Selecta ran a pair of phase 3 trials that compared two doses of ImmTOR, combined with a fixed dose of pegadricase, to placebo in patients with gout that was refractory to conventional therapy. None of the participants had previously received Krystexxa or other experimental or approved therapies based on uricase.
In the first trial, the response rates in the low- and high-dose cohorts were 48% and 56%, respectively, compared to 4% in the placebo cohort. The difference in the second trial was smaller, with 41% and 47% response rates in the low- and high-dose cohorts playing off against 12% in the placebo group, but was still statistically significant. Both doses in both clinical trials met the primary endpoint.
The trials defined response as maintaining a reduction in serum uric acid less than 6 mg/dL for at least 80% of the time during month six. The phase 3 trials of Krystexxa looked at the proportion of people who had plasma uric acid of less than 6 mg/dL for at least 80% of the time during month three and Month 6. The response rates for the commercial Krystexxa monotherapy regimen in the trials were (PDF) 47% and 38%, although a methotrexate combination that was approved last year acheived a 71% response rate.
Krystexxa is given every two weeks—a four-week regimen failed in one of the phase 3 trials—and that gives Selecta and Sobi an advantage. SEL-212 was given every four weeks in Selecta’s phase 3 program. With patients staying on Krystexxa for up to one year, halving the administration frequency could spare people from receiving six to 12 doses.
One question going into the SEL-212 trial was whether the candidate could reduce gout flares, which can occur as enzyme therapies break down urate deposits. In the first three months of the Krystexxa trials, 74% of patients on the two-week regimen experienced gout flares, compared to 51% of people on placebo.
The situation reversed over the next three months, with the Krystexxa rate falling to 41% as the placebo rate rose to 67%, but the data still offered a potential point of differentiation for Selecta and Sobi. The SEL-212 release states there was “one gout flare in both the high and low dose treatment group” and that “there was no difference in gout flares when both treatment groups were compared to placebo.”
Selecta and Sobi are holding off on sharing a closer look at the data until an upcoming medical meeting. A filing for approval in the U.S. is planned for the first half of next year. Shares in Selecta rose 22% to $1.57 in premarket trading, while Sobi opened down slightly in trading in Sweden.