탈모치료제 CTP-543이 기대되는 이유

최근 탈모 치료제 CTP-543의 치료효과가 이슈가 된 적이 있습니다. 극적으로 대머리가 단 몇 주 만에 머리가 풍성해졌기 때문입니다. 하지만 이미 JAK inhibitor로 원형 탈모제가 있습니다. 단지 CTP-543가 좀 더 효과가 더 빨리, 더 좋습니다. 홍보 효과가 좋았다고 생각도 듭니다. 하지만 이 약물은 유전적인 탈모에는 효과 없어서 제한적인 사용만 가능합니다. 그래도 원형탈모 환자도 많이 있으니 그래도 많은 사람들이 혜택 받을 거라 생각됩니다. 

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1. CTP-543

Generic Name	Deuruxolitinib
Molecular Weight	313.414
MOA	JAK1, JAK2 inhibitors
Therapeutic Group	Hair Growth Stimulation
Highest Phase	Phase III
Prescription/Designation	Breakthrough Therapy Designation, Fast Track Designation

CTP-543

Concert라는 회사는 물질의 수소를 중수소를 치환하는 기술력이 있는 것 같습니다. Ruxolitinib이라는 약물에 중수소를 치환하여 Deuruxolitinib, CTP-543을 개발하고 임상 3상을 진행하고 있습니다. 

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2. 탈모 분류 (Classification of Alopecia)

탈모 구별

탈모에는 여러 종류가 있습니다. 크게는 국부적인 탈모와 전신에서는 나타나는 탈모가 있습니다. 그중에서 CTP-543의 타겟은 원형탈모 (Alopecia areata)입니다. 

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3. 원형 탈모 (Alopecia Areata)

원형 탈모

1) 원형탈모는 치료가 어려운 면역 질환입니다 (autoimmune disease).

2) Alopecia Areata occurs worldwide

• Prevalence of approx. 0.2% of the US population with a lifetime risk of 1.7 –2%*

3) Chronic condition affecting women, men and children of all ages

• Disease profoundly impacts patients; associated with anxiety, depression and other autoimmune conditions

3) No FDA-approved treatment options

• >FDA PFDDI meeting (September 2017) on alopecia areata highlighted patient experience and need for treatment

The impact of alopecia areata extends beyond cosmetic concerns and carries a considerable psycho-social burden

Nearly all clinicians and patients in this study agreed that, for patients with at least 50% scalp-hair loss, successful treatment would be hair regrowth resulting in ≤ 20% scalp-hair loss (-> 80% scalp coverage)

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 4. Market size

마켓 사이즈

유전적인 탈모와 면역질환으로써 원형 탈모 시장이 비슷한 정도의 시장 크기를 가지고 있습니다.  그만큼 CTP-543의 시장이 넓다고 할 수 있습니다.

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5. The Role of Janus Kinase (JAK) in Alopecia Areata

Alopecia Areata anagen follicle

1) JAK is a family of intracellular tyrosine kinases that play a central role in the signaling of cytokine and growth factor receptors

• Therapies targeting downstream JAK effectors have shown efficacy in autoimmune disorders such as atopic dermatitis, psoriasis, and RA

2) Alopecia areata is an autoimmune disorder characterized by non-scarring hair loss affecting scalp and body hair

3) Proposed mechanism of hair loss in alopecia areata: cytotoxic T cell attack of the hair follicle after loss of immune privilege, regulated by JAK signaling

4) Various JAK inhibitors are in clinical-stage testing and show promise as a class in treating alopecia areata

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6. CTP-543 개발 과정

 

7. CTP-543: 임상 2상 시험 (Phase 2 Dose-Ranging Trial)

• at least 50% hair loss as measured by Severity of Alopecia Tool (SALT)
• Primary Endpoint: 50% relative reduction in SALT at Week 24 from baseline
• Sequentially randomized to receive one of three doses of CTP-543 (4, 8,12 mg BID) or placebo for 24 weeks

3) Primary endpoint met with statistical significance for 8 mg and 12 mg doses at Week 24

• >12 mg responders average 86% SALT improvement
• >8 mg responders average 78% SALT improvement

4) Significant patient reported Global Impression of Improvement

Response over treatment priod

Response over Treatment priod; CTP-543

Response over Treatment priod; CTP-543

 

1) The primary efficacy endpoint of ≥50% relative reduction in SALT at Week 24 was met for 8 mg BID and 12 mg BID

2) Dose-related improvements for 8 mg BID and 12 mg BID across all efficacy assessments

•   Significant SALT improvement as early as Week 12

3) At Week 24, 8 mg BID and 12 mg BID significantly different from placebo on percent of patients achieving a clinically-meaningful SALT score ≤ 20

•   Patients achieving a SALT score ≤ 20 is primary efficacy endpoint in Phase 3 program

4) Good feedback through patient-reported outcome measures

5) CTP-543 treatment was generally well-tolerated

•   More than 90% of patients completing Phase 2 trials rolled into long-term extension study

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A Phase III Study to Evaluate the Efficacy and Safety of CTP-543 in Adult Patients With Moderate to Severe Alopecia Areata

The main objective of the trial: The overall objectives of the study are to assess the efficacy and safety following administration of CTP-543 in adult patients with moderate to severe alopecia areata.

The primary objectives of the study are to assess: The efficacy of CTP-543 on regrowth of hair following 24 weeks of treatment. The safety of CTP-543 following 24 weeks of treatment.

Percentage of patients achieving an absolute Severity of Alopecia Tool (SALT) score ≤20 [ Time Frame: Week 24 ]

SALT is a quantitative assessment of scalp hair loss with scores ranging from 0 (no scalp hair loss) to 100 (complete scalp hair loss).

The secondary objectives of the trial: The secondary objectives of the study are to assess: Clinician and patient-reported impression of the severity and improvement of alopecia areata. Patient-reported satisfaction with their scalp hair. Patient-reported levels of anxiety and depression. Changes in eyebrows and eyelashes.

 

Inclusion Criteria

• Adult subjects with moderate-to-severe alopecia areata • Patients age 18 to 65 years with>/= 50% hair loss • Clinical presentation compatible with alopecia areata with a current episode lasting at least 6 months and not exceeding ten years at the time of Screening. Total disease duration > 10 years is permitted • At least 50% scalp hair loss, as defined by a SALT score >/= 50, at screening and baseline • Willing to comply with the study visits and requirements of the study protocol

Exclusion Criteria

• Treatment with other medications or agents within 1 month of baseline or during the study that may affect hair regrowth or immune response • Active scalp inflammation, psoriasis, or seborrheic dermatitis requiring topical treatment to the scalp, significant trauma to the scalp, or other scalp condition that may interfere with the SALT assessment, or untreated actinic keratosis anywhere on the body at screening and/or baseline •Treatment with systemic immunosuppressive medications within 3 months of screening or during the study, or biologics within 6 months of screening or during the study •Females who are nursing, pregnant, or planning to become pregnant while in the study, and for 30 days after last dose of study drug •Clinically significant medical condition, psychiatric disease, or social condition, as determined by the Investigator, that may unfavorably alter the risk-benefit of study participation, adversely affect study compliance, or confound interpretation of study result.

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Concert Pharmaceuticals Reports Positive Topline Results for First CTP-543 Phase 3 Clinical Trial in Alopecia Areata

1) Primary endpoint는  24주차에 SALT 점수 20 이하를 달성한 환자의 비율 >>bid 8mg, 12mg 모두 통계적 유의성을 충족함.

2) 등록된 환자는 SALT로 측정한 원형 탈모증으로 인한 두피 탈모는 50%이상이며, SALT 평균은 85.9점 이었음.

•   SALT 달성한 환자 비율은 12mg(bid): 41.5%, 8mg(bid): 29.6%

3) THRIVE-AA1에서 CTP-543의 안전성 프로파일은 이전 연구와 일치함. 모든 용량 그룹에서 가장 흔한(≥5%) 부작용은 두통, 여드름, 상기도 감염, 크레아틴 키나아제 수치 증가, COVID-19 감염 및 비인두염임. 심각한 부작용은 9명의 환자에서 보고되었으며, 단 한 명의 환자(8mg 1일 2회 투여 그룹)에서 치료와 관련될 수 있는 것으로 평가됨. 심각한 부작용을 보고한 4명의 환자는 위약군임