The first drug treatment for vitiligo! Opzelura (ruxolitinib) cream: significantly improves facial & systemic skin lesions repigmentation!

October 25, 2022 /BioValleyBIOON/ --Incyte Corporation today announced that data from a pivotal Phase 3 TRuE-V clinical program evaluating Opzelura (ruxolitinib, ruxolitinib, 1.
5% cream) for topical treatment of nonsegmental vitiligo in patients 12 years of age and older has been published in the New England Journal of Medicine (NEJM).

。 See: Two Phase 3, Randomized, Controlled Trials of Ruxolitinib Cream for Vitiligo
.

The data showed that the two phase 3 trials (TRuE-V1, TRuE-V2) of the project met both the primary and key secondary endpoints: after 24 weeks of treatment, patients in the Opzelura cream treatment group had a significant improvement
in facial and systemic skin lesion repigmentation compared with the excipient-cream treatment group.
The 52-week data showed continued improvement
in lesion repigmentation with longer treatment time.
In this project, Opzelura cream did not report clinically significant site reactions and had an overall good
safety profile.

In July 2022, Opzelura (1.
5% cream) received FDA approval for a new indication: it is a nonsteroidal, anti-inflammatory, topical JAK inhibitor for the topical treatment of nonsegmental vitiligo
in adults and adolescents (age > 12 years).
。 It is worth mentioning that Opzelura is the first and only drug approved by the US FDA for the treatment of vitiligo for skin repigmentation (repigmentation), and it is also the only JAK inhibitor topical preparation
approved by the agency.

Vitiligo is a chronic autoimmune disease characterized by skin depigmentation, a skin condition caused by the loss of pigment-producing melanocytes (melanocyte) that often affects beauty and beauty
.
Overactivity of the JAK signaling pathway is thought to drive inflammation
involved in the pathogenesis of vitiligo and disease progression.
Vitiligo affects about 0.
5%-2.
0% of the world's population
.
In the United States, more than 1.
5 million people have been diagnosed with vitiligo, the total number of cases is estimated at 2-3 million, and the majority of patients (about 85%) have nonsegmental vitiligo
.
Vitiligo can occur at any age, but many patients experience initial symptoms
before the age of 30.

Opzelura (ruxolitinib cream) clinical project data (Image source: NEJM)

The TRuE-V program includes two Phase 3 studies, TRuE-V1 (NCT04052425) and TRuE-V2 (NCT04057573), conducted in adolescents and adults (≥ 12 years of age) patients with vitiligo, each enrolling approximately 300 patients diagnosed with non-segmental vitiligo (NSV) with depigmented areas.
To assess the efficacy and safety
of Opzelura cream as monotherapy.
In the study, patients were randomized to receive 1.
5% Opzelura cream twice daily (BID) or excipient-controlled cream BID for a 24-week double-blind period
.
Patients who successfully completed the baseline examination and 24-week assessment, including those receiving excipient-controlled creams during the double-blind phase, entered a 28-week open-label treatment extension period given 1.
5% Opzelura cream BID for 28 weeks
.

The data showed that at week 24, the results of the two studies were consistent: approximately 30% of patients in the Opzelura cream BID group achieved a 75% ≥improvement in the Regional Score Index of Facial Vitiligo (F-VASI) from baseline (F-VASI 75), significantly higher than in the excipient-controlled cream BID treatment group (TRuE-V1 study: 29.
9% vs 7.
5%; TRuE-V2 study: 29.
9 versus 12.
9 percent).

At week 52, 50% of patients who received Opzelura cream from day 1 achieved F-VASI 75
.

Furthermore, at week 24, more than 15% of patients in the Opzelura cream BID group achieved a 90% improvement in F-VASI from baseline (F-VASI 90) in ≥ 1.
5% of patients treated with Opzelura cream BID, compared with only about 2%
in the excipients group.
At week 52, the proportion of patients in the Opzelura cream group who reached F-VASI 90 doubled to about 30 percent
.

At week 52, a higher proportion of patients achieved a ≥ 50% improvement in the regional score index (T-VASI) from baseline (T-VASI50) and a further improvement
in the percentage change in facial body surface area (F-BSA) compared to baseline after Opzelura.

During the excipient control period of the Phase 3 study, the most common adverse reactions (incidence ≥ 1%) were acne at the treatment site, itching at the treatment site, nasopharyngitis, headache, urinary tract infection, erythema at the medication site, and fever
.

Ruxolitinib Chemical Structural Formula

Opzelura cream is a proprietary formulation of Incyte's selective Janus kinase 1 and Janus kinase 2 (JAK1/JAK2) inhibitors ruxolitinib and is designed
for topical application.
Incyte has the worldwide rights to develop and commercialize ruxolitinib cream for the treatment of mild to moderate atopic dermatitis and for the treatment of vitiligo in adolescents and adults
.

In September 2021, Opzelura (ruxolitinib cream) received FDA approval for its first indication for short-term and non-ongoing chronic treatment in adolescents (age ≥ 12 years) and adults with mild to moderate atopic dermatitis (AD) who have not adequately controlled the condition with topical prescription therapies or when these therapies are not desirable and are not
immunocompromised.
The drug is the only topical preparation
of JAK inhibitors approved by the US FDA.
Studies have shown that dysregulation of the JAK-STAT pathway leads to key features of AD, such as pruritus, inflammation, and skin
barrier dysfunction.
In a Phase 3 clinical study, Opzelura treatment significantly reduced AD-related skin inflammation and itching
.
Reducing pruritus has the potential to improve key disease-related and quality-of-life outcomes
in people with AD.

ruxolitinib is also the active pharmaceutical ingredient of Incyte's oral drug Jakafi, which has been approved in the United States for 3 indications: (1) the treatment of adult patients with polycythemia (PV) who have an inadequate response to or intolerance to mercaptouria; (2) Treatment of adult patients with intermediate- and high-risk myelofibrosis (MF), including primary MF, MF after PV, and MF after primary thrombocytosis; (3) Treatment of steroid-refractory patients with acute graft-versus-host disease (GVHD).

Among them, the third indication was approved by the FDA in May 2019, which is the first drug
approved to treat a single indication.
Jakafi is sold by Incyte in the U.
S.
, and Novartis sells
under the Jakavi brand name outside the U.
S.

At present, Concert is also developing the ruxolitinib molecule CTP-543 modified with deuterium chemical technology, which has shown strong efficacy
in the treatment of alopecia areata in phase II clinical studies.
Alopecia areata is an autoimmune disease that causes partial or complete hair
loss.
Deuterium chemical modifications of ruxolitinib can alter its human pharmacokinetics, thereby enhancing its use
as a treatment for alopecia areata.
In the United States, the FDA has granted CTP-543 fast-track status
for the treatment of alopecia areata.
(Bio Valley Bioon.
com)

Pivotal Phase 3 Data Showing Significant Improvements In Facial And Total Body Repigmentation With Ruxolitinib Cream (Opzelura?) In Vitiligo Published In New England Journal Of Medicine