Interaction Review

Dr. Nguyen, thank you for meeting with me today at the hepatology conference. I understand you've been following the autoimmune hepatitis landscape closely.

Yes, Marcus. I manage a large cohort of AIH patients at our liver center, and I'm always looking for better options beyond azathioprine and prednisone. Tell me about Clarovexa's mechanism.

Clarovexa is a selective JAK1/TYK2 inhibitor designed specifically for hepatic autoimmune conditions. Unlike broad JAK inhibitors, its selectivity profile was engineered to minimize the hematologic effects we've seen with less selective agents.

Interesting. I've been concerned about the thrombotic events associated with JAK inhibitors in the rheumatology space. How does the safety data look specifically for liver patients?

That's a critical question. In the CLARION Phase IIb trial with 480 AIH patients, the incidence of thromboembolic events was 0.4%, which was not statistically different from placebo at 0.2%. The study did exclude patients with pre-existing thrombotic risk factors, so that's an important consideration.

What about ALT normalization rates? That's really the primary endpoint I care about.

At 52 weeks, 67% of patients on Clarovexa achieved complete ALT normalization versus 29% on standard of care. The median time to normalization was 14 weeks, which is notably faster than what we typically see with conventional immunosuppression.

Those are compelling numbers. Are there any histological endpoints? I'd want to see liver biopsy improvements.

Yes, in the subset of patients who underwent paired biopsies at baseline and week 52, there was a 2.1-point improvement in the modified HAI score with Clarovexa compared to 0.8 points with standard of care. It's worth noting that this was a secondary endpoint and the biopsy subset was relatively small at 120 patients.

I appreciate you being transparent about the limitations. What about the steroid-sparing potential? Many of my patients are struggling with long-term prednisone side effects.

In the CLARION trial, 71% of patients on Clarovexa were able to completely discontinue corticosteroids by week 36, compared to 23% in the standard of care arm. The protocol allowed for a structured steroid taper beginning at week 8.

That steroid-sparing data is really what my patients need. Is there an investigator-initiated trial program? I'd be interested in studying Clarovexa in overlap syndromes.

We do have an IIT program. I can connect you with our clinical operations team to discuss your research concept. I should note that any IIT would need to go through our medical review process and your IRB, of course.

Excellent. Let's set that up. Also, are there any upcoming advisory boards where I could contribute?

We're planning a national advisory board in Q2 focused on treatment sequencing in AIH. I'll make sure your name is put forward for consideration. I'll follow up with the details via email this week.