Martina J. Porter, MD: Immunogenicity of Secukinumab for Hidradenitis Suppurativa

During an interview at the 2024 American Academy of Dermatology (AAD) Annual Meeting, Martina J. Porter, MD, of Harvard Medical School, spoke with HCPLive about the phase 3 findings of the SUNSHINE and SUNRISE trials on secukinumab for hidradenitis suppurativa (HS).1,2

Porter highlighted her team’s findings demonstrating that secukinumab therapy had resulted in sustained efficacy. She discussed the trials’ results and the findings on the drug’s immunogenicity in patients with HS.

“This was an analysis that was performed from the phase 3 data for SUNSHINE and SUNRISE, which is secukinumab,” Porter explained. “And it's actually now FDA-approved for hidradenitis suppurativa or HS in both the US and Europe as well. The study itself enrolled about 1000 patients, and it was a moderate-to-severe population. They received 2 dosing arms, either every 2 weeks or every 4 weeks for maintenance. The dose was 300 milligrams, which is the same as what we use for the psoriasis dosing.”

Porter noted that many patients have been shown to have developed anti-drug antibodies, even at drug levels that clinicians would have considered to be therapeutic in patients such as those with inflammatory bowel disease for example.

“But we never had identified levels until recently from some of the work that we've done to target these TNF-alpha inhibitors,” Porter said. “So when we're talking about secukinumab in our psoriasis data, we've always seen that they have very low levels of immunogenicity, and we were wondering if the same thing existed in our HS population.”

Porter’s team had found that the overall treatment-emergent anti-drug antibody (TE-ADA) incidence in this new analysis was shown to be 0.6% and 0.8% in SUNSHINE and SUNRISE, respectively.

“What they found was that there were very, very low levels of treatment-emergent anti-drug antibodies,” she explained. “There were only 3 in the SUNSHINE study, and there were 4 total in SUNRISE. And this is almost 500 patients.”

The research team’s findings indicated that TE-ADAs had been non-neutralizing. They added that they were linked to normal secukinumab pharmacokinetics and that none had a connection with any adverse events or efficacy loss.

“I think that we're learning a lot about anti-drug antibodies in dermatology, because we had sort of started to see them in our psoriasis data many years ago and then didn't really need to look at them anymore because IL-17 and IL-23 inhibitors really didn't have any of these anti-drug antibodies and they were much more efficacious therapies. In HS, when we look at the outcomes for TNF-alpha inhibitors like adalimumab, and we compare the data to secukinumab which can't be done head to head…the numbers actually aren't that far off, in terms of what we see in efficacy of the drug versus placebo.”

Porter noted that adalimumab, from a cost perspective, will probably end up being first line treatment for a lot of patients on their formularies. Nevertheless, she noted that some patients are very prone to making these anti-drug antibodies because they either have some sort of genetic haplotype or have high inflammation.

Such patients may benefit from IL-17 inhibitors, because they are known to have much lower risk of immunogenicity. Porter noted that the low immunogenicity of secukinumab may allow such patients to maintain their response for months to years, based on some of this data.

To learn more, view the full interview segment posted above.

The quotes contained here were edited for clarity.

References

1. ^{Kimball AB, et al. Secukinumab demonstrates low immunogenicity in patients with moderate-to-severe hidradenitis suppurativa: Results from placebo-controlled, double-blind, Phase 3 SUNSHINE and SUNRISE trials. Oral presentation (Abstract #52241) at the American Academy of Dermatology (AAD) 2024 Annual Meeting. March 2024.}
2. ^{Kimball AB, et al. Secukinumab in moderate-to-severe hidradenitis suppurativa (SUNSHINE and SUNRISE): week 16 and week 52 results of two identical, multicentre, randomised, placebo-controlled, double-blind phase 3 trials. Lancet. 2023; 401:747–61.}