SEL-212
pegadricase + ImmTOR™
SEL-212 is a novel, once-monthly co-administration of pegylated uricase (pegadricase; SEL-037) with ImmTOR™, an immune tolerance technology designed to inhibit formation of anti-drug antibodies (ADAs). For this application, the ImmTOR consists of SEL-110.36, an inhibitor of uricase-specific ADA. This could help address the limitation of reduced efficacy and tolerability in the presence of ADAs developed in response to other biologic medicines (e.g., KRYSTEXXA®; pegloticase; Amgen) for chronic gout.
About SEL-212
- Sobi
- Cartesian Therapeutics Inc/Selecta Biosciences Inc
- ImmTOR™ (nanoparticles encapsulating sirolimus [SEL-110.36]) + pegylated uricase (pegadricase; SEL-037)
- Once-monthly intravenous infusion to treat chronic refractory gout
- 19.7m prevalent cases of chronic gout in the G7 markets in 2023
Why is it a drug to watch?
Sobi licensed SEL-212 from Selecta Biosciences Inc (acquired by Cartesian Therapeutics Inc in November 2023) for $100m and is responsible for development, regulatory and commercial activities in all markets except Mainland China. It is expected to be the first drug for treatment-refractory chronic gout in the European and Japanese markets.
SEL-212 was designed to reduce serum urate levels in chronic refractory gout, thereby reducing harmful tissue urate deposits that can result in gout flares and joint deformity when left untreated. Administration involves sequential infusions of ImmTOR (SEL-110.36), followed by SEL-037. Phase 3 results revealed similar efficacy and safety to that of KRYSTEXXA, the main competitor in the treatment of chronic refractory gout. However, SEL-212 has less-frequent dosing and is co-administered with an immunomodulator, whereas KRYSTEXXA can require follow-up administration of methotrexate for immunomodulation when needed.
The rolling BLA submission was based on results from the pivotal phase 3 DISSOLVE I and DISSOLVE II trials:
-
Both RCTs had the same inclusion criteria and treatment regimen:
-
Adults (19-80 years old) with chronic gout refractory to conventional therapies (xanthine oxidase inhibitors [XOIs], uricosurics) and not previously exposed to pegylated uricase-based therapy
-
Treatment arms (administered every 28 days for six months)
-
Low-dose SEL-212: 0.1 mg/kg SEL-110.36, followed by SEL-037
-
High-dose SEL-212: 0.15 mg/kg SEL-110.36, followed by SEL-037
-
Placebo
-
DISSOLVE I (United States); n=112
-
Achieved and maintained a reduction in serum uric acid levels <6 mg/dL for at least 80% of the trial duration: 48% vs 56% vs 4%
-
DISSOLVE II (global); n=153
-
Achieved and maintained a reduction in serum uric acid levels <6 mg/dL for at least 80% of the trial duration: 40% vs 46% vs 11%
-
In both trials, the active treatment groups experienced mild-to-moderate stomatitis (3.4% vs 9.2%), infusion reactions (4.5% vs 3.4%). Serious TEAEs included anaphylaxis and gout flare (3.4% of all participants receiving active treatment).
Review and approval status
March 2024
- Fast track designation: U.S. FDA
July 2024
- Rolling BLA submitted: U.S. FDA
Actual and expected launch:
- 2025: United States
- 2026: European Union, Japan
Drug Timeline & Success Rates
Source: Cortellis Competitive Intelligence, Drug Timeline & Success Rates Prediction current as of October 31, 2024
How will SEL-212 impact the market for gout?
-
Major market sales of drugs for acute and chronic gout will increase from $3.6bn in 2023 to $8.6bn in 2033, driven primarily from the launch and uptake of emerging therapies and the increased incidence and prevalence of gout over the forecast period.
-
At the same time, market value could be constrained by the limited number of assets in late-stage development and the availability of inexpensive generic options, which effectively treat most individuals with gout. Generic options will likely remain the standard of care due to their low price, satisfactory efficacy and physician familiarity.
-
In the chronic gout market specifically, SEL-212 is expected to drive substantial sales growth because of its anticipated high price, which is expected to be at approximately a 10% premium to KRYSTEXXA, and successful positioning for chronic gout refractory to other treatments.
-
SEL-212 could also have a competitive edge over KRYSTEXXA, its main competitor, given its similar efficacy and safety profile, less-frequent dosing and co-administration with an immunomodulator. In the first months following launch, KRYSTEXXA achieved sales of $507m, providing an indicator of the potential for SEL-212.
What gaps in treatment does SEL-212 fill?
In the United States, KRYSTEXXA is the only option for individuals whose chronic gout does not respond to standard treatments but is not currently approved in Europe nor Japan, representing a large gap for patients with chronic refractory gout in these markets. Treatment-refractory chronic gout is often painful and debilitating, resulting in several flares per year and potential nodular masses of uric acid crystals (tophi). In markets where KRYSTEXXA is available, SEL-212 is expected to be a welcome option for patients and clinicians given its once monthly infusion and co-administration of two separate drugs, compared with KRYSTEXXA’s biweekly administration and the need to administer it with methotrexate.
What hurdles might it need to overcome to reach blockbuster status?
Despite its potential competitive edge over KRYSTEXXA, uptake of SEL-212 might be limited by the relatively small target population of patients with chronic refractory gout (~2% of individuals with gout), its extremely high price and the expected launch of biosimilar versions of KRYSTEXXA pegloticase) starting in 2030.
