8-K: Kezar Life Sciences Announces Positive Phase 2a Trial Results for Zetomipzomib in Autoimmune Hepatitis and Reports Year-End Financials

Kezar Life Sciences reports positive topline results from the PORTOLA Phase 2a trial of zetomipzomib in autoimmune hepatitis (AIH), showing steroid-sparing biochemical remissions and reports year end 2024 financial results.

Summary

• Kezar Life Sciences announced positive topline results from the PORTOLA Phase 2a clinical trial evaluating zetomipzomib for the treatment of patients with autoimmune hepatitis (AIH).
• The trial showed that zetomipzomib treatment resulted in steroid-sparing biochemical remissions in a difficult-to-treat, refractory AIH patient population.
• In relapsed, steroid-dependent AIH patients, 36% (5 of 14) of zetomipzomib-treated patients achieved a complete biochemical response (CR) and clinically significant steroid taper to 5 mg/day or less, compared to 0 of 7 of placebo patients.
• In the intention-to-treat (ITT) population, 31% (5 of 16) of zetomipzomib patients achieved a CR and steroid taper (5 mg/day), compared to 1 of 8 placebo patients.
• The median duration of response in zetomipzomib patients achieving a CR was 27.6 weeks, and no disease flares were reported in any zetomipzomib-treated patient achieving CR during the study.
• The company reported cash, cash equivalents, and marketable securities totaling $132 million as of December 31, 2024.
• The company plans to work with the FDA to remove the partial clinical hold and align on an appropriate trial design to demonstrate the clinical benefit of zetomipzomib in AIH.

Sentiment

Score: 8

Explanation: The document presents positive clinical trial results and a solid financial position, suggesting a favorable outlook for the company. However, the presence of adverse events and the need to address the clinical hold temper the overall optimism.

Positives

• The PORTOLA trial showed positive topline results for zetomipzomib in AIH patients.
• Zetomipzomib treatment resulted in higher rates of complete biochemical responses (CR) combined with reduction of steroid dosage to 5 mg/day or less, compared to placebo.
• The median duration of response in zetomipzomib patients achieving a CR was 27.6 weeks.
• A favorable safety profile was observed during the 6-month, blinded treatment period.
• The company has $132.2 million in cash, cash equivalents, and marketable securities as of December 31, 2024.

Negatives

• Treatment-emergent adverse events (TEAEs) were seen in all patients, with injection site reactions (ISRs) being the most commonly reported TEAE in both arms.
• Three patients discontinued from the zetomipzomib arm for a Grade 1 fatigue, Grade 2 hives and a Grade 2 AIH disease flare.
• Revenue decreased by $7.0 million in 2024 compared to 2023.

Risks

• The company is awaiting the removal of a partial clinical hold by the FDA.
• The development and regulatory approval of zetomipzomib are subject to uncertainties and risks.
• The company's future results and performance could differ materially from those expressed or implied by forward-looking statements.

Future Outlook

Kezar anticipates aligning with the FDA and EMA on a potential registrational study in AIH, pending the removal of the partial clinical hold.

Management Comments

• We are pleased to announce these exciting results from the PORTOLA trial, the first successful randomized study in treatment-refractory AIH, said Chris Kirk, CEO and co-founder of Kezar.
• I am impressed by the totality of efficacy and safety data from the PORTOLA study, said Gideon Hirschfield, Chair of Autoimmune Liver Disease Research and Director of the Francis Family Liver Clinic, at the Toronto General Hospital.

Industry Context

The announcement addresses a significant unmet need in the treatment of autoimmune hepatitis, a chronic liver disease with limited treatment options beyond standard immunosuppressants. The positive results from the PORTOLA trial position zetomipzomib as a potential novel therapy in this space.

Comparison to Industry Standards

• Current standard of care for AIH involves long-term use of corticosteroids and immunosuppressants, which often have significant side effects.
• The AASLD treatment guidelines emphasize biochemical normalization and low daily steroid dose as treatment goals.
• The reported 36% complete response rate with steroid taper in the zetomipzomib-treated group compares favorably to the outcomes typically achieved with standard of care in refractory AIH patients.
• Companies like Intercept Pharmaceuticals and CymaBay Therapeutics are also developing therapies for liver diseases, but zetomipzomib's unique mechanism of action as a selective immunoproteasome inhibitor differentiates it from other approaches.

Stakeholder Impact

• Shareholders may react positively to the clinical trial results and financial update.
• Patients with AIH may benefit from the development of a new treatment option.
• Employees of Kezar Life Sciences may be affected by the company's strategic decisions and clinical development programs.

Next Steps

• Kezar will respond to all FDA Division of Hepatology partial clinical hold comments as quickly as possible.
• Presentation of PORTOLA results at a major medical conference is planned for second half 2025.
• Kezar looks forward to aligning with the FDA and EMA on a potential registrational study in AIH, pending removal of partial clinical hold.

Key Dates

Keywords

zetomipzomib, autoimmune hepatitis, AIH, PORTOLA trial, clinical trial, biochemical remission, steroid-sparing, Kezar Life Sciences, immunoproteasome inhibitor