Delgocitinib

None Watch out, Incyte. Leo Pharma and its JAK inhibitor cream delgocitinib are coming to disrupt the topical atopic dermatitis market, currently inhibited by Incyte’s approved Opzelura. With several positive studies in hand, including a recent phase 3 trial pitting the candidate against the current standard-of-care, Leo says its delgocitinib has growth driver potential. Now, the drugmaker will be “investing additional resources in accelerating the launch of this potential treatment to patients,” Leo said in its first quarter earnings release. The cream is currently under regulatory review in Europe. As for other markets including the U.S., Leo is “assessing ways” to bring the potential treatment to commercialization, it said. Delgocitinib has been marked in Japan by Japan Tobacco for four years now. Leo's evidence supporting the drug includes two phase 3 studies against a placebo cream and an open-label extension study proving its success in treating patients with moderate-to-severe chronic hand eczema. Most recently, delgocitinib went up against standard-of-care alitretinoin capsules, the only currently approved treatment for chronic hand eczema patients who do not respond to topical corticosteroids. In the DELTA FORCE study of 513 patients, Leo’s candidate proved a superior reduction in scoring on the Hand Eczema Severity Index at week 12 and week 24. It also trumped alitretinoin in two other secondary measures assessing treatment success and quality of life. “We are confident that with the DELTA FORCE study, delgocitinib cream may play a crucial role in expanding the options available for patients in this hard-to-treat condition,” chief development officer Kreesten Meldgaard Madsen said at the time. If the drug scores approval, it would compete with the only other marketed topical JAK inhibitor, Incyte’s Opzelura. That med is a cream version of the company’s popular JAK inhibitor Jakafi. Other than atopic dermatitis, Opzelura is also approved to treat vitiligo. Incyte is now moving to expand the Jakafi counterpart into pediatric atopic dermatitis use and expects to submit its bid for the indication this year along with “multiple data readouts,” head of R&D Pablo Cagnoni said on the company’s first-quarter earnings call. A pediatric nod would add some two million to three million eligible patients to the med’s reach, the company said. Opzelura and Jakafi brought Incyte to blockbuster fourth-quarter sales last year, reflecting what the company’s North America general manager Barry Flannelly called “one of the best recent dermatology launches” on Opzelura’s part following its 2021 approval. More recently over this year’s first quarter, sales for both Opzelura and Jakafi sank on a quarterly basis, missing analyst’s consensus. While Jakafi was impacted by higher inventory drawdown and Opzelura by Change Helathcare’s cyberattack, the explanations “still will not provide investors with data point to suggest there is upside to estimates in the near term,” analysts at William Blair wrote in a note to clients. Opzelura pulled first-quarter revenues of $86 million, dipping 21.5% from the fourth quarter.

在美国皮肤病学会（ AAD ）年会上，利奥制药延续了其强劲势头，用最新突破报告分享了关键 DELTA 3 试验的积极结果。 1 该试验研究了 Delgocitinib 乳膏治疗中重度慢性手部湿疹（ CHE ）成人患者的疗效。 结果显示，研究药物 Delgocitinib 乳膏的安全性和有效性特征与之前 DELTA 1 和 2 试验的结果一致。 1 同时， DELTA 系列试验在安全性、有效性和系统暴露方面的新数据也在会议上公布，进一步完善了 Delgocitinib 乳膏的广泛数据。 2,3,4 圣地亚哥 2024年3月19日 /美通社/ -- 2024 年 3 月 9 日， 在美国圣地亚哥举行的第 82 届 AAD 大会上，利奥制药首次公布了 Delgocitinib 乳膏 DELTA 3 试验的关键结果。 1 这个报告是利奥制药在 AAD 会议上两项 Late-Breaking 报告中的第一项。本次会议，利奥制药共有八篇摘要被接收。 在 DELTA 3 中，在母试验 DELTA 1 或 DELTA 2 中完成 16 周治疗期的受试者根据治疗需求接受 Delgocitinib 乳膏治疗（每日两次）以控制其慢性手部湿疹，治疗持续 36 周。如果疾病在 36 周之内得到控制，则后续可以不进行治疗。 1 DELTA 3 扩展试验（ N=801 ）旨在评估 Delgocitinib 乳膏按需治疗的长期安全性。研究结果显示，未发现新的安全性问题。这表明 Delgocitinib 乳膏的安全性与 DELTA 1 和 DELTA 2 临床试验的积极结果一致。 1 最常见的治疗期出现的不良事件（ TEAE ）为 COVID-19 和鼻咽炎。 1 DELTA 3 扩展试验的关键次要终点中的有效性结果也与母试验 DELTA 1 和 2 一致。在母试验中接受 Delgocitinib 乳膏治疗的受试者中，达到研究者慢性手部湿疹总体评估（ IGA-CHE ）评分 0/1 （清除 / 几乎清除）和手湿疹严重程度指数（ HECSI ）改善 ≥75% 和改善 ≥90% 的患者比例在第 36 周（分别为 30.0% 、 58.6% 和 36.6% ）较基线（分别为 24.6% 、 51.8% 和 31.8% ）增加。在母试验中接受乳膏赋形剂治疗的患者中，相应的应答率在第 36 周（分别为 29.5% 、 51.5% 和 35.7% ）较基线（分别为 9.1% 、 23.7% 和 12.0% ）增加。 1 利奥制药首席开发官 Kreesten Meldgaard Madsen 表示： “ 此次报告是利奥制药在为解决慢性手部湿疹患者关键未被满足需求的前进道路上所取得的又一里程碑式的突破。在 AAD 上首次公布 DELTA 3 结果，让我们有机会证明我们致力于解决这种疾病所带来的巨大医疗负担的决心。我们希望能通过在重要皮肤病大会上不断分享我们的关键数据，推动 Delgocitinib 乳膏作为一种潜在的新治疗选择的临床开发。 ” 主要研究者、 SKiN 皮肤病中心 医疗总监 Melinda Gooderham 博士表示： “ 慢性手部湿疹患者一直以来仅有极少数的治疗选择， DELTA 3 的研究结果为他们带来了新的希望。 ” 同时在本次 AAD 会议上 DELTA 1 和 2 试验的安全性、有效性和系统暴露方面的最新数据也以电子海报的形式公布。 2,3,4 关于 DELTA 1 ， 2 和 3 试验 DELTA 1 和 DELTA 2 是随机、双盲、赋形剂对照、多中心的 III 期临床试验，其主要目的是评估每日两次使用 Delgocitinib 乳膏与乳膏赋形剂相比在治疗成人中度至重度 CHE 方面的疗效。 5,6 DELTA 1 和 DELTA 2 试验的主要终点是第 16 周研究者慢性手部湿疹总体评估的治疗成功（ IGA-CHE TS ）。治疗成功定义为 IGA-CHE 评分为 0 （清除）或 1 （几乎清除），且较基线至少改善两分。 第 16 周的关键次要终点包括从基线到第 16 周，依据手部湿疹症状日记（ HESD ）评估的瘙痒和疼痛评分减少 ≥4 分，以及第 16 周手部湿疹严重程度指数（ HECSI ）较基线至少改善 75% 和至少改善 90% 。试验的关键安全性终点是从基线到第 16 周的治疗中出现的不良事件数量。 在 DELTA 1 或 DELTA 2 试验中，完成 16 周 Delgocitinib 乳膏或乳膏赋形剂治疗（每日两次）的患者有机会入组 DELTA 3 扩展试验。该扩展试验旨在评估每日两次接受 Delgocitinib 乳膏按需治疗的长期安全性。受试者每 4 周在门诊接受一次访视，以评估治疗的安全性和有效性，以及对患者报告结果（ PRO ）的影响，直到完成 36 周的随访，并在第 38 周对受试者进行最终电话随访。 1 关于慢性手部湿疹 慢性手部湿疹（ CHE ）是指持续三个月以上或一年内复发两次或以上的手部湿疹（ HE ）。 7,8 HE 是最常见的手部皮肤病 9 ， 1 年患病率（ one-year prevalence rate ）约为 9% 。 10 大多数的 HE 患者都会进展成为一种慢性疾病。 9 CHE 是一种以瘙痒和疼痛为特征的波动性疾病，患者的手部和腕部可能会出现红斑、鳞屑、苔藓样变、角化过度、水疱、水肿和皲裂等症状。 11 已证明 CHE 会造成心理和功能负担，影响患者的生活质量， 12 约 70% 的严重 CHE 患者认为该疾病对日常活动造成了影响。 13 此外，也有证据表明 CHE 也会影响到患者的工作和收入。 14 关于 Delgocitinib Delgocitinib 乳膏是一款 “first-in-class” 的在研、外用泛 Janus 激酶（ JAK ）抑制剂，用于治疗 CHE 。其可抑制 JAK-STAT 信号的激活，而 JAK-STAT 信号在 CHE 的发病机制中起着关键作用。 15 CHE 的病理生理学的特点是皮肤屏障功能障碍、皮肤炎症和皮肤微生物组的改变。 16 利奥制药目前正在开发 Delgocitinib 的乳膏剂型，用于治疗成人中度至重度慢性手部湿疹（ CHE ）。 2014 年，利奥制药和日本烟草公司（ Japan Tobacco Inc. ， JT ）达成许可协议，利奥制药获得了除日本外在全球范围内开发和商业化 Delgocitinib 乳膏（外用）治疗皮肤病适应症的独家权利， JT 保留在日本的权利。 Delgocitinib 乳膏尚未获得任一国家卫生当局的批准。 关于利奥制药 利奥制药是一家引领标准治疗，惠及皮肤疾病患者及其家庭和社会的全球公司。利奥制药成立于 1908 年，大部分股权隶属于利奥基金会，数十年来一直致力于研发，以推动皮肤病科学的发展。如今，利奥制药为不同严重程度的疾病提供了广泛的治疗方案。利奥制药总部位于丹麦，拥有全球员工 4600 人，为全球数千万患者提供服务。 2023 年，利奥制药的净销售收入为 114 亿丹麦克朗。 在中国，利奥制药专注于银屑病、特应性皮炎和皮肤感染 3 大疾病领域，是相关疾病领域的市场领导者，通过有竞争力的产品和服务来提高人们的生活质量。 参考文献 Gooderham M, et al. Long-term safety and efficacy of delgocitinib cream for up to 36 weeks in adults with Chronic Hand Eczema: results of the Phase 3 open-label extension DELTA-3 trial. Presented at the 2024 American Academy of Dermatology Annual Meeting; March 8-12 2024 ; San Diego , CAx Bissonnette R, et al. Efficacy and safety of delgocitinib cream in adults with moderate to severe chronic hand eczema: pooled results of the Phase 3 DELTA-1 and -2 trials. Presented at the 2024 American Academy of Dermatology Annual Meeting; March 8-12 2024 ; San Diego, CA. Bauer A, et al. Delgocitinib cream reduces itch and pain in adults with moderate to severe chronic hand eczema: pooled analyses of the Phase 3 DELTA-1 and -2 trials. Presented at the 2024 American Academy of Dermatology Annual Meeting; March 8-12 2024 ; San Diego, CA. Gooderham M, et al. Systemic exposure and safety profile of delgocitinib cream in adults with moderate to severe chronic hand eczema in the Phase 3 DELTA-2 trial. 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