On April 1st, Kangzhe Pharmaceutical announced a partnership with Incyte regarding the selective oral administration of the JAK1 inhibitor Povorcitinib, obtaining exclusive licensing rights for the product in China and Southeast Asia.
Povorcitinib is used to treat multiple autoimmune and inflammatory skin diseases such as non segmental vitiligo (ongoing overseas phase III) and purulent sweat gland inflammation (ongoing overseas phase III), and has the potential to become the best daily oral medication of its kind in related skin therapies.
The vitiligo market is huge and there are urgent clinical needs to be met. What is the competitive landscape?
Vitiligo is a chronic autoimmune disease caused by a decrease or disappearance of tyrosinase activity in melanocytes in the skin and hair follicles, leading to a reduction or disappearance of melanin particle formation and resulting in localized or generalized depigmentation of the skin and mucous membranes. It can occur in various parts of the body and is commonly seen in the back of fingers, wrists, forearms, face, neck, etc.
The global incidence of vitiligo is about 0.5% -2%, with approximately 22.83 million vitiligo patients in China, and it is more common among adolescents. According to PharmaONE data from the China Pharmaceutical Industry Information Center, the global vitiligo drug market is expected to achieve rapid growth, reaching $4.91 billion by 2024. From the epidemiology of vitiligo, the patient population is large and tends to occur in young people, and the treatment demand for vitiligo is huge and urgent.
The drug treatment for vitiligo includes hormone therapy, immunosuppressive agents, vitamin D derivatives, etc. However, existing treatment plans have certain drawbacks, such as the long dosing cycle of hormone therapy and the possibility of systemic adverse reactions. Therefore, it cannot be used for a long time, otherwise it may cause drug dependence or resistance.
Among biological preparations, only Lucretinib cream has been approved as an indication for vitiligo worldwide. There is no specific medication approved for the market for vitiligo. Currently, mainstream vitiligo treatment drugs include calcineurin inhibitors (tacrolimus cream), glucocorticoids (dexamethasone cream), and vitamin D3 derivatives (carpotriol cream), but none have been approved for vitiligo indications. Only Lucretinib cream has been approved for vitiligo globally, but it can only be used in the Boao Medical Pilot Zone in Hainan. Overall, the choice of medication for vitiligo is limited, and there is still a huge unmet clinical demand in the market.
At present, Lucotinib cream is the only JAK inhibitor approved by the FDA for the treatment of vitiligo and skin lesion discoloration. It can be used for local treatment of non segmental vitiligo patients aged 12 years and above. The research targets for vitiligo are concentrated on JAK inhibitors, PDE4 inhibitors, interleukin inhibitors, etc.
(1) OPZELURA cream was developed by Incyte and is a local topical JAK inhibitor. It was approved by the FDA for local treatment of non segmental vitiligo patients aged 12 years and above in July 2022. In December 2022, Kangzhe Pharmaceutical announced to introduce the exclusive development and commercialization rights and interests of Lucotinib cream in Chinese Mainland, Hong Kong, Macao, Taiwan and eleven countries in Southeast Asia.
The FDA approved the use of Lucetinib cream for local treatment of non segmental vitiligo in adults and children aged 12 and above based on data from two Phase III clinical trials (TruE-V1 and TruE-V2). More than 600 non segmental vitiligo patients aged 12 years and above were enrolled in two trials, and the safety and efficacy of OPZELURA were compared with the placebo group. At 24 weeks of treatment, the results showed that the OPZELURA treatment group significantly improved the VASI score of patients compared to the control group. The patient's facial and surface skin discoloration rates were significantly improved, and this improvement persisted and became more significant at 52 weeks. At 52 weeks of re evaluation, 75% of patients reached F-VASI50, indicating a skin lesion improvement of more than or equal to 50% from baseline; About 50% of patients achieved F-VASI75, which means that the improvement in skin lesions from baseline is greater than or equal to 75%.
On December 11, 2023, Lucetinib cream received a drug clinical trial approval notice from the National Medical Products Administration (NMPA) of China, agreeing to conduct a phase III clinical trial to evaluate the safety and efficacy of the product in treating non segmental vitiligo.
(2) Litexitinib is an orally bioavailable small molecule that can inhibit the JAK3 and TEC kinase families. Currently, the indications for vitiligo are in clinical stage III. In a phase IIb study, researchers explored the efficacy and safety of rituxantinib in the treatment of non segmental vitiligo patients.
The research results showed that a total of 364 patients were treated within the dose range. Compared with placebo, the percentage of change in the facial vitiligo area score index was significantly improved (n=187) in the loaded dose (-21.2 vs2.1; P<0.001) or unloaded dose (-18.5 vs2.1; P<0.001) of rituxantinib 50mg group and 30mg group (-14.6 vs2.1; P=0.01). During the 48 week treatment period, no dose-dependent trend of treatment induced or serious adverse events was observed. The research results indicate that oral rituxantinib is effective and well tolerated in the treatment of active non segmental vitiligo patients for more than 48 weeks.
(3) Povorcitinib is an oral JAK1 inhibitor small molecule drug developed by Incyte, and clinical trials are currently underway for diseases such as vitiligo, purulent sweat gland inflammation, and nodular prurigo.
A total of 171 patients were included in the Phase II study, and the results showed that at week 24, the T-VASI of patients in different dose groups (15mg, 45mg, 75mg) receiving Povorcitinib treatment decreased by -19.1%, -17.8%, and -15.7% relative to baseline, respectively. Compared with the placebo group (+2.3%), the decrease was significantly improved, and the difference was statistically significant.
At week 52, pigmentation improved in all treatment groups. Among them, the average T-VASI reduction relative to baseline in the Povorcitinib treatment group was -40.7%, -42.7%, and -41.3%, respectively, while in the placebo group it was -18.1%. 34 patients entered the follow-up period, of which 32 completed the 76th week of follow-up. From week 52 to week 76, the median changes in T-VASI for the four treatment groups were 2.1%, 4.9%, 21.0%, and -0.4%, respectively, indicating that even with discontinuation of Povorcitinib, patients can still maintain treatment efficacy.
In terms of safety, the incidence of treatment-related adverse events (TEAEs) and severe adverse events (SAEs) in patients treated with Povorcitinib 45mg and 75mg for 52 weeks was 89.2% and 2.4%, respectively. The most common TEAEs include COVID-19 (36.1%), elevated blood creatine kinase (13.3%), acne (12.0%), fatigue (10.8%), and headache (9.6%).
(4) CKBA is a subsidiary of Taienkang, led by Professor Wang Honglin's team, based on the natural product acetyl-11ketone in frankincense- β- The structural modification, design, and screening of first in class (FIC) drug molecules using Mastic Acid (AKBA). CKBA regulates cellular lipid metabolism by targeting ACC1 and MFE2, inhibiting CD8+T cells from producing effector molecules and exerting effector functions. CKBA ointment is currently undergoing phase II clinical trials for vitiligo indications, and the first patient was enrolled in November 2023.
(5) The active ingredient of MH004 is a JAK inhibitor developed by Minghui Pharmaceutical using its proprietary technology. MH004 is expected to improve skin permeability and achieve widespread targeted inhibition of local skin tissue without the systemic toxicity of existing oral JAK inhibitors.
On January 19, 2024, Minghui Pharmaceutical registered a Phase II clinical trial (CTR20240183) on the drug clinical trial registration and information disclosure platform, aiming to evaluate the preliminary efficacy, safety, tolerability, and pharmacokinetic characteristics of MH004 cream in non segmental vitiligo patients. This study aims to include 156 patients clinically diagnosed with non segmental vitiligo in China, with the main endpoint being the proportion of subjects who improved their facial vitiligo area score index by at least 50% (F-VASI50) from baseline after 24 weeks of MH004 cream treatment.
The global population of vitiligo patients is huge, and there is an urgent need for targeted drugs to be launched. At present, the research and development pattern of vitiligo is good, and the crowding level of the track is low. If the under development variety is successfully launched, it is expected to quickly fill the market gap and grow into a heavyweight variety. Opzelura (Lucretinib Cream), a subsidiary of Incyte, achieved revenue of $338 million (+162%) in 2023 and is rapidly increasing in sales due to its indication for vitiligo. Focusing on the domestic market, Kangzhe Pharmaceutical has introduced Lucretinib cream and Povorcitinib. Taienkang's CKBA and Minghui Pharmaceutical's MH004 are in clinical phase II, and we look forward to excellent data reading.
