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POVORCITINIB – WHAT YOU NEED TO KNOW ABOUT THIS POTENTIAL NEW TREATMENT

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Povorcitinib – what you need to know about this potential new treatment

 Posted on 7th February 2024  5 minute read

Incyte is one of the world leading companies in dermatological auto-immune disease research. They developed ruxolitinib which is now a licensed vitiligo treatment in the US under the name Oplezura.

Recently, at the European Academy of Dermatology and Venereology (EADV) Congress in 2023, Incyte announced the results of their phase 2 trial evaluating a new possible vitiligo treatment – a compound called Povorcitinib (Incyte, 2023b).

What is Povorcitinib?

Povorcitinib, also known under the drug ID number INCB54707 belongs to the family of janus kinase (JAK) inhibitors (Kirby et al., 2023). The JAK signalling pathway has been found to be central to the inflammation causing vitiligo. JAK inhibitors block that pathway and stop it from working which indirectly contributes to repigmentation and disappearance of white patches in individuals with vitiligo (Qi et al., 2021). Multiple JAK inhibitors have been researched, such as Tofacitinib or Ritlecitinib developed by Pfizer or previously mentioned Ruxolitinib by Incyte.

The thing that makes povorcitinib different from those other compounds is that it a selective JAK-1 inhibitor (Kirby et al., 2023). The JAK family consists of four members and the drugs that inhibit the JAK signalling pathway might inhibit any or all of them. For example, Ruxolitinib inhibits JAK1 and JAK2 (Rosmarin et al., 2022). The potential advantage of Povorcitinib being selective to JAK1 is that it might reduce the occurrence of low blood cell counts that have been contributed to JAK2 inhibitors (Akada et al., 2014 in Alavi et al., 2022).

Povorcitinib appears to be effective for treatment of other auto-immune conditions. The drug is in trials for vitiligo, hidradenitis suppurativa, prurigo nodularis, chronic spontaneous urticaria and asthma (Incyte, 2023b).

Povorcitinib and vitiligo – a recent phase 2 trial

The most recent trial of Povorcitinib in vitiligo was completed in May 2023. While the study has not yet been published in a scientific journal, Incyte has announced some of the results at the EADV Congress in October 2023. The study was a 52-week phase 2 trial investigating the effectiveness of Povorcitinib in adults with nonsegmental vitiligo (study ID number NCT04818346). One-hundred seventy-one individuals aged 18-75 years old were recruited. Every participant had nonsegmental vitiligo affecting at least 8% of their body surface area.

The participants were randomly assigned to four treatment groups following different drug regimes. In the first 24 weeks of the trial, each group received the following dose of Povorcitinib daily by mouth: group 1 – 15 mg, group 2 – 45 mg, group 3 – 75 mg and placebo group received placebo. After the 24 weeks, until week 52, the doses were adjusted as follows: group 1 received 75mg, group 2 – 45mg, group 3 – 75 mg, placebo 75 mg. Such a regime may seem a bit confusing, but it is necessary to find out the most optimal dose and regime for treatment. The study refers to the four groups as 15-75mg group, 45mg group, 75mg group, placebo-75mg group.

What did the study measure?

A few outcomes were measured to accurately determine the effectiveness of povorcitinib. The main outcomes were Total Vitiligo Area Scoring Index (T-VASI) and Facial Vitiligo Area Scoring Index (F-VASI). The indexes can be thought of in such a way that a 50% improvement in T-VASI (score of -50%) indicates that the total area of vitiligo (white patches) on the body decreased by 50%. Similarly, if it the FVASI decreased by 50% then that means that the vitiligo area on the face decreased by 50%. The study also measured the percentage of participants that achieved a 50% improvement in T-VASI (T-VASI50), and 50% and 75% improvements in F-VASI (F-VASI50 and F-VASI75 accordingly).

Incyte reported the results at 24 and 52 weeks (Incyte 2023a, Incyte 2023b). The specific results are summarized in Table 1. Overall, the response to povorcitinib has been excellent. It has been found very effective at repigmentation of vitiligo patches at all dosages. Over the 52 weeks, more than 1/3 of participants had achieved T-VASI50 and F-VASI75. Moreover, the 32 participants that completed the follow-up at week 76 (24 weeks after they stopped Povorcitinib) have found that the repigmentation was maintained which shows that the effects of the treatment appear to be long lasting. Overall, Povorcitinib was well tolerated and participants did not experience any serious side effects. Around 10% experienced some acne, tiredness, and headaches. While Povorcitinib seems to be very effective for vitiligo treatment, it is important to keep in mind that the positive findings need to be replicated in a larger group of individuals to confirm it works in people of different backgrounds.

Table 1. Summary of the results of the NCT04818346 study announced by Incyte.

What happens now?

There are currently two phase 3 studies in patient recruitment phase. Both STOP-V1 (NCT06113445) and STOP-V2 (NCT06113471) started recruiting patients with vitiligo in November 2023. Each study aims to enrol 444 participants. The results should be announced by May 2027.

While the long wait time may seem discouraging, these trials are necessary to ensure the safety of Povorcitinib. Although it is not yet available on the market, the fact that it’s being researched is a positive thing as there are not many treatments available for vitiligo that are as effective as this drug appears to be. For more information on vitiligo treatments, please visit our website at https://vitiligosociety.org/.


References

Akada, H., Akada, S., Hutchison, R., Sakamoto, K., Wagner, K. U., & Mohi, G.(2014). Critical role of JAK2 in the maintenance and function of adult hematopoietic stem cells. Stem Cells, 32(7), 1878–1889. https://doi.org/10.1002/stem.1711

Alavi, A., Hamzavi, I., Brown, K., Santos, L. L., Zhu, Z. W., Liu, H., Howell, M. D., & Kirby, J. S. (2022). Janus kinase 1 inhibitor INCB054707 for patients with moderate‐to‐severe hidradenitis suppurativa: results from two phase II studies*. British Journal of Dermatology, 186(5), 803–813. https://doi.org/10.1111/bjd.20969

Incyte. (2023a, March 18). Incyte announces data from phase 2b study evaluating povorcitinib (INCB54707) in patients with extensive nonsegmental vitiligo [Press release]. https://investor.incyte.com/news-releases/news-release-details/incyte-announces-data-phase-2b-study-evaluating-povorcitinib

Incyte. (2023b, October 11). Incyte announces positive 52-week data from phase 2b study evaluating povorcitinib (INCB54707) in patients with extensive nonsegmental vitiligo | incyte [Press release]. https://investor.incyte.com/news-releases/news-release-details/incyte-announces-positive-52-week-data-phase-2b-study-evaluating

Kirby, J. S., Okun, M., Alavi, A., Bechara, F. G., Zouboulis, C. C., Brown, K. N.,Santos, L. L., Wang, A., Bibeau, K., Kimball, A. B., & Porter, M. L. (2023). Efficacy and safety of the oral Janus kinase 1 inhibitor povorcitinib (INCB054707) in patients with hidradenitis suppurativa in a phase 2,randomized, double-blind, dose-ranging, placebo-controlled study. Journal of the American Academy of Dermatology. https://doi.org/10.1016/j.jaad.2023.10.034

Qi, F., Liu, F., & Gao, L. (2021). Janus kinase inhibitors in the Treatment of Vitiligo: a review. Frontiers in Immunology, 12. https://doi.org/10.3389/fimmu.2021.790125

Rosmarin, D., Passeron, T., Pandya, A. G., Grimes, P. E., Harris, J. E., Desai, S. R., Lebwohl, M., Ruer‐Mulard, M., Séneschal, J., Wolkerstorfer, A., Kornacki, D., Sun, K., Butler, K., & Ezzedine, K. (2022). Two phase 3, randomized, controlled trials of ruxolitinib cream for vitiligo. The New England Journal of Medicine, 387(16), 1445–1455. https://doi.org/10.1056/nejmoa2118828

About the Author

Katarzyna Stefanska

Katarzyna Stefanska is a 3rd year medical student at the University of Edinburgh, currently intercalating in a Physical Activity for Health Honours programme. Although still at the beginning of her medical journey, Kat utilises her scientific literature review skills to write up-to-date, plain language summaries of different aspects of vitiligo to help those living with the condition make more informed choices and provide answers to any queries they might have.

Katarzyna Stefanska is a 3rd year medical student at the University of Edinburgh, currently intercalating in a Physical Activity for Health Honours programme. Although still at the beginning of her medical journey, Kat utilises her scientific literature review skills to write up-to-date, plain language summaries of different aspects of vitiligo to help those living with the condition make more informed choices and provide answers to any queries they might have.