The Global Biosimilar Development and Approval of Yesintek With Elena Wolff-Holz, MD

Elena Wolff-Holz, MD, global head of clinical development at Biocon Biologics, discussed the recent approval of BMAb-1200 (Yesintek; ustekinumab-kfce) as a biosimilar to reference ustekinumab (Stelara) to treat psoriasis.

Wolff-Holz emphasized the comparable efficacy and safety results observed, including pre- and postswitch data, while acknowledging challenges in patient recruitment and navigating diverse global regulatory requirements.

This transcript was lightly edited for clarity; captions were auto-generated.

Transcript

What specific clinical end points or patient-reported outcomes did you find most compelling in support of the study comparing BMAb-1200 with reference ustekinumab?

Well, maybe just a few introductory statements, so BMAb-1200 is now an approved drug. It just got recently approved and is called Yesintek [ustekinumab-kfce] here in the United States and will also be launched in Europe and Japan in the next few weeks.

The clinical basis, the clinical study, the phase 3 trial that was conducted in support of the marketing authorization application, was a clinical trial that lasted 52 weeks. It was a double-blind randomized trial in 384 patients, and they were rerandomized; those patients that received the originator drug Stelara were rerandomized at week 16 to either continue on the Stelara or get the BMAb-1200, and then all patients were followed in a blind fashion until week 52.

In terms of end points, the primary end point, and I think that was the most compelling, was at week 12. That's important because it's sort of in the steep part of the dose-response curve, and you can really, if there was a difference, you would detect it at that time point. Actually there was, in terms of change of the PASI [Psoriasis Area and Severity Index] score from baseline, there was absolutely no difference.

The FDA and also EMA, they have certain requirements on how they define confidence intervals. The 2 drugs must be within this confidence interval, and [for] FDA plus/minus 10% is allowed. We had a difference of 0.68%, so that's very compelling primary end point results. Above and beyond, we've also looked at week 4, 8, 16, and 20-week data, and that was also highly similar. We looked at preswitch and postswitch data, and again, the switching would not have any impact with regard to the PASI score or safety or immunogenicity.

These are all very important findings, and I would think, in summary, those are the most important ones, but there's also the PsA [psoriatic arthritis], actually, and they were also comparable. All of this gives a very comprehensive story.

What were the most significant challenges encountered during the study, and how were they addressed? What lessons were learned that could benefit future biosimilar development?

This was a global study at 41 centers, 5 countries, and 384 patients, so recruiting these patients on time. We had a global development that would satisfy all the legislations, including PMDA [Pharmaceuticals and Medical Devices Agency], that is Japan's regulatory body. At that time, we were asked to have at least 15% Japanese patients, and that was a challenge to include. Luckily, the Japanese regulators now have changed this demand. It's no longer required. It also introduced heterogeneity. That's something we would change, and we would be allowed to change.

Otherwise, I think anything that enhances inspection readiness would be of advantage. I think we've implemented checkpoints already in the trial, but this is something also in terms of monitoring continuity from the CRO [contract research organization] site to the sites. I think that's something I would take more care even to have this continuity so one particular CRA [clinical research associate] or CRM [clinical research management] [is] really being available for the entire study and beyond to carry through, also the inspections.