Calliditas announces positive TRANSFORM Phase 2b topline data in primary biliary cholangitis

Rhea-AI Summary

Calliditas Therapeutics AB (NASDAQ: CALT) announced positive topline results from its Phase 2b TRANSFORM trial evaluating setanaxib in patients with primary biliary cholangitis (PBC) and elevated liver stiffness. The study met its primary endpoint, showing statistically significant improvement in Alkaline Phosphatase (ALP) for both tested doses versus placebo. Key findings include:

- 19% ALP improvement in the 1600mg arm
- 14% ALP improvement in the 1200mg arm
- Positive trends on liver stiffness at 24 weeks
- Generally well-tolerated treatment
- Efficacy demonstrated in patients already on multiple medications

The company is conducting additional trials with setanaxib, including a Phase 2 trial in idiopathic pulmonary fibrosis (IPF) and a Phase 2 proof of concept trial in Alport syndrome.

Positive

• Phase 2b TRANSFORM trial met its primary endpoint with statistically significant ALP improvement
• 19% ALP improvement in the 1600mg arm and 14% in the 1200mg arm
• Positive trends observed on liver stiffness at 24 weeks
• Efficacy demonstrated in patients already on multiple medications
• Additional ongoing trials for setanaxib in IPF and Alport syndrome

Negative

• Higher frequency of treatment emergent adverse events leading to study discontinuation in active treatment groups compared to placebo

Medical Research Analyst

The positive Phase 2b TRANSFORM trial results for setanaxib in primary biliary cholangitis (PBC) patients are highly significant for Calliditas Therapeutics. As a Medical Research Analyst, I find several key points noteworthy:

• The trial met its primary endpoint with statistically significant improvements in Alkaline Phosphatase (ALP) levels: 19% reduction in the 1600mg arm and 14% in the 1200mg arm compared to placebo.
• Importantly, over 40% of trial participants were on dual therapy and 13% on triple therapy, suggesting setanaxib provides incremental benefits beyond current standard of care.
• Positive trends in liver stiffness reduction were observed, although specific data wasn't provided.
• The safety profile appears generally favorable, with similar overall adverse event rates between treatment and placebo groups.

These results are particularly impressive given the challenging patient population and relatively small sample size of 76 patients. The data supports setanaxib's potential as a first-in-class NOX inhibitor for PBC treatment, especially for patients with inadequate response to current therapies.

However, it's important to note that this is a Phase 2b trial and larger Phase 3 studies will be necessary to confirm efficacy and safety. The higher discontinuation rate in the treatment group also warrants further investigation in future trials.

Financial Analyst

From a financial perspective, these positive Phase 2b results for setanaxib in PBC are a significant milestone for Calliditas Therapeutics. Here's why this news is particularly impactful:

• Market Potential: PBC is a rare disease with treatment options. A novel therapy showing efficacy could capture substantial market share.
• Competitive Advantage: As a first-in-class NOX inhibitor, setanaxib could differentiate Calliditas in the PBC market, potentially commanding premium pricing.
• Pipeline Validation: Success in PBC validates Calliditas' NOX platform, potentially increasing investor confidence in other pipeline candidates using the same technology.
• Near-term Catalysts: With additional readouts expected in Q4 2024/Q1 2025 for IPF and 2025 for Alport syndrome, Calliditas has multiple value-driving events on the horizon.

However, investors should consider that:

• Significant R&D expenses will likely continue as setanaxib progresses to Phase 3 trials.
• Commercialization is still years away, assuming successful completion of the clinical development program.
• As a small-cap biotech, Calliditas may need additional financing to fund late-stage development and potential commercialization efforts.

Overall, while risks remain, this news significantly de-risks Calliditas' lead program and could attract increased investor interest in the near term.

Market Research Analyst

As a Market Research Analyst, I see several key implications of Calliditas' positive Phase 2b results for setanaxib in PBC:

• Unmet Medical Need: PBC affects approximately 130,000 people in the US and has treatment options. A new therapy showing efficacy could rapidly gain market share.
• Competitive Landscape: Current treatments include ursodeoxycholic acid (UDCA) and Ocaliva (obeticholic acid). Setanaxib's ability to show benefits in patients already on these therapies is a significant competitive advantage.
• Market Expansion: By potentially addressing patients with inadequate response to current therapies, setanaxib could expand the treatable PBC patient population.
• Pricing Potential: As a novel, first-in-class therapy for a rare disease, setanaxib could command premium pricing if approved.
• Future Indications: Success in PBC could pave the way for setanaxib's development in other fibrotic diseases, expanding its market potential.

However, challenges remain:

• Regulatory hurdles and the need for larger Phase 3 trials before potential approval.
• Educating physicians on a new mechanism of action (NOX inhibition) in PBC treatment.
• Potential competition from other novel therapies in development for PBC.

Overall, these results position Calliditas favorably in the PBC market, with potential for significant market penetration if further development is successful.

STOCKHOLM, July 26, 2024 /PRNewswire/ -- Calliditas Therapeutics AB (NASDAQ: CALT) (STOCKHOLM: CALTX) ("Calliditas") today announced that the Phase 2b TRANSFORM trial met its primary endpoint, showing statistically significant improvement in ALP (Alkaline Phosphatase) for both doses tested versus placebo. The trial evaluated setanaxib, a NOX enzyme inhibitor, in patients with primary biliary cholangitis (PBC) and elevated liver stiffness.

The TRANSFORM trial is a double-blind, randomized, placebo-controlled Phase 2b study investigating the effect of setanaxib 800 mg AM + 400 mg PM, ("1200 mg arm") and 800 mg BID ("1600 mg arm") over 24 weeks of treatment. The basis for the analysis consisted of a dataset of 76 patients with primary biliary cholangitis (PBC) and elevated liver stiffness.

The treatment groups were relatively well-balanced with no clinically relevant differences between the groups observed at baseline. The result is particularly encouraging as over 40% of the trial population was on dual therapy, ie was receiving UDCA (ursodeoxycholic acid) and either Ocaliva (obeticholic acid) or Bezafibrate (PPAR agonist) as base therapy and 13% were receiving all three therapies during the study, reflecting setanaxib having clinically relevant incremental benefit beyond existing standard of care. Patients treated with setanaxib showed statistically significant improvements in the primary endpoint of ALP of 19% in the 1600mg arm and 14% in the 1200mg arm and showed positive trends on liver stiffness assessed by FibroScan® at 24 weeks. Setanaxib treatment was generally well tolerated with overall number of TEAEs (treatment emergent adverse events), as well as serious TEAEs, being similar between active treatment and placebo. The frequency of TEAEs leading to study discontinuation was higher in patients receiving active treatment compared to placebo.

"It is very encouraging to see a statistically significant treatment effect in this hard-to-treat population which is already on multiple medications in this relatively small study," said Professor Dave Jones OBE; Director, NHIP Academy; Director, Newcastle Centre for Rare Disease; Professor of Liver Immunology, Newcastle University; and Honorary Consultant Hepatologist, Newcastle upon Tyne Hospitals.

"These positive data provide further clinical evidence of the potential of setanaxib in multiple rare diseases, and we are very pleased that we now have additional positive clinical evidence in support of our unique, first in class NOX platform. We also look forward to the read out of the investigator led study in IPF as well as the ongoing study in Alport syndrome in due course," said CEO Renée Aguiar-Lucander.

"I am delighted that we have seen statistically significant and clinically meaningful improvements in ALP with encouraging trends in other outcomes in this population of patients with PBC. I'd like to extend my thanks to investigators, clinical trial site staff, and most importantly patients, who have all contributed to this important study," said CMO Richard Philipson.

The company is conducting additional clinical trials with setanaxib and is expecting the investigator led Phase 2 trial in IPF (idiopathic pulmonary fibrosis) to provide top line data in Q4 2024 / Q1, 2025. There is also an ongoing Phase 2 proof of concept trial in Alport syndrome, which is expected to deliver top line data in 2025.

For further information, please contact:
Åsa Hillsten, Head of IR & Sustainability, Calliditas
Tel.: +46 76 403 35 43, Email: asa.hillsten@calliditas.com

The information was sent for publication, through the agency of the contact persons set out above, on July 26, 2024 at 08:00 a.m. CET.

This information was brought to you by Cision http://news.cision.com

https://news.cision.com/calliditas-therapeutics/r/calliditas-announces-positive-transform-phase-2b-topline-data-in-primary-biliary-cholangitis,c4018789

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SOURCE Calliditas Therapeutics

FAQ

What were the main results of Calliditas' TRANSFORM Phase 2b trial for setanaxib (CALT)?

The TRANSFORM Phase 2b trial met its primary endpoint, showing statistically significant improvement in Alkaline Phosphatase (ALP) for both tested doses of setanaxib versus placebo in patients with primary biliary cholangitis (PBC) and elevated liver stiffness. The 1600mg arm showed a 19% ALP improvement, while the 1200mg arm showed a 14% improvement.

How did setanaxib (CALT) perform in terms of safety in the TRANSFORM trial?

Setanaxib was generally well-tolerated in the TRANSFORM trial. The overall number of treatment emergent adverse events (TEAEs) and serious TEAEs were similar between active treatment and placebo groups. However, the frequency of TEAEs leading to study discontinuation was higher in patients receiving active treatment compared to placebo.

What other clinical trials is Calliditas conducting for setanaxib (CALT)?

Calliditas is conducting additional clinical trials with setanaxib, including an investigator-led Phase 2 trial in idiopathic pulmonary fibrosis (IPF) expected to provide top-line data in Q4 2024 / Q1 2025, and an ongoing Phase 2 proof of concept trial in Alport syndrome, expected to deliver top-line data in 2025.

What is the significance of the TRANSFORM trial results for Calliditas (CALT)?

The positive TRANSFORM trial results provide further clinical evidence of setanaxib's potential in multiple rare diseases and support Calliditas' unique, first-in-class NOX platform. The efficacy demonstrated in patients already on multiple medications suggests setanaxib could offer additional benefits beyond existing standard of care treatments for primary biliary cholangitis.