On March 21, Selecta Biosciences and Sobi announced positive pivotal results from two phase III studies (DISSOLVE I and DISSOLVE II). These two placebo-controlled, randomized clinical trials were designed to evaluate the safety and efficacy of two different dose levels of SEL-212 in adult patients with chronic refractory gout. Gout is an autoinflammatory disease in which patients experience severe pain and debilitating inflammatory arthritis due to deposits of pro-inflammatory sodium urate (MSU) crystals. Patients with chronic refractory gout often have a high tissue MSU burden, which can lead to frequent gout attacks and chronic arthritis. Gout is the most common inflammatory arthritic disease in the United States. SEL-212 has the potential to reduce serum uric acid and MSU deposition in patients with chronic refractory gout. Recombinant uricase is highly immunogenic in the human body. Through Selecta's proprietary ImmTOR platform, SEL-212 has the potential to alleviate the formation of anti-drug antibodies, which can be conveniently administered once a month to improve the efficacy and tolerance of uricase. Receptivity. Pegsiticase (also known as pegadricase, a recombinant enzyme that can metabolize uric acid), was developed by 3SBio. In 2014, 3SBio authorized Selecta to develop it into SEL-212 using the company's ImmTOR® immune tolerance platform.

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.

Link: https://www.fiercebiotech.com/biotech/planning-challenge-horizon-selecta-and-sobi-rout-gout-pair-phase-3-trials