Stemchymal® for PolyQ SCA
Stemchymal® 應用於脊髓小腦萎縮症之治療
- 認識脊髓小腦萎縮症
Background of polyglutamine SCAs (PolyQ SCA)
脊髓小腦萎縮症(Spinocerebellar Ataxia, SCA）是一種罕見的神經退化性疾病，又稱為小腦萎縮症，會導致身體協調能力逐漸惡化。一般而言，SCA的盛行率大約是每10萬人中有1到5個案例1。目前已發現有超過48種不同的SCA亞型，主要會影響小腦（尤其是普爾金細胞）、腦幹和其他非脊髓小腦組織。許多SCA亞型都是由不同的基因突變所引起的，包括SCA1、SCA2、SCA3、SCA6、SCA7和SCA17在內的SCAs皆是由CAG重複序列所引起的，該序列編碼使特定的蛋白質中有過多的麩醯胺酸(glutamine, Q)累積，故該疾病又稱為PolyQ SCAs。所有PolyQ SCAs患者在臨床上表徵上都會出現肢體和步態失調，進而演進成各種行為失能。PolyQ SCAs是一種危及生命的疾病，通常好發於20歲到50歲不等，在疾病的演進過程中，同時會給患者的家庭和醫療保健提供者帶來了沉重的負擔。Spinocerebellar Ataxia (SCA) is a rare neurodegenerative disease that cause progressive difficulty with coordination. In general, the prevalence of SCA is about 1~5 cases per 100,000 persons1. There is more than 48 subtypes of SCA that involve the cerebellum (in particular Purkinje cells), brainstem, and other non-spinocerebellar tissues. Among the subtypes, polyglutamine SCAs (PolyQ SCAs) including SCA1, SCA2, SCA3, SCA6, SCA7 and SCA17 are caused by an extensive CAG sequence repeat which encodes for expanded polyQ residues within the mutated protein. All PolyQ SCAs patients clinically present limb and gait ataxia because the same ataxia interactome is shared among these different sub-groups.
- 脊髓小腦萎縮症的臨床照護
Clinical management of PolyQ SCA
目前臨床上尚未有上市的藥物可以延緩或停止脊髓小腦萎縮症的進展。現行療法主要以支持性、緩解或減輕症狀頻率和嚴重程度的治療，包括以物理治療改善步態異常，以及透過語言治療幫助患口齒不清的患者等。Unfortunately, no curative therapy has been approved which can delay or halt the progression of PolyQ SCAs. Currently, there are only therapies approved for PolyQ SCAs which provide supportive, palliative treatment in relieving or reducing the frequency and severity of symptoms. Physical therapy to ameliorate gait dysfunction and speech therapy for patients with dysarthria are also essential supportive treatments.
- 脊髓小腦萎縮症的臨床進展
Steminent’s progress in PolyQ SCA
仲恩在台灣已完成 Stemchymal® 治療 PolyQ SCAs 的 I/II 期臨床試驗及II期臨床試驗。在I/II期臨床試驗中，病患在12 個月的追蹤期中未觀察到與Stemchymal®相關的不良事件，證明了 Stemchymal® 的安全性。在療效評估方面，我們採用共濟失調評估和評級量表(Scale for the Assessment and Rating of Ataxia, SARA)與感官定向測試評量(Sensory Orientation Test)來評估療效。在單次輸注 Stemchymal® 後的第一個月，66% 的受試者的 SARA 評分和 SOT 評分均有所改善，改善的效果可維持長達 6 個月。該研究成果已發表於Cell Transplant 2017； 26(3)：503-512。Steminent has completed a phase I/II and a phase II clinical trials in Taiwan with Stemchymal® for the treatment of PolyQ SCA. In the phase I/II trial, no cell-related adverse event was observed in the 12-month follow up, demonstrating the safety of Stemchymal®. Moreover, evidence of potential efficacy was observed in the preliminary Phase I/II data from two efficacy assessments: Scale for the Assessment and Rating of Ataxia (SARA) and the Sensory Orientation Test (SOT). Sixty-six percent of the subjects showed improvement in both the SARA score and the SOT score in the first month following a single infusion of Stemchymal®. These measured functional improvements were maintained in study subjects for up to 6 months. The results were published in Cell Transplant 2017; 26(3): 503-512.
為進一步研究 Stemchymal® 治療 PolyQ SCAs 的安全性和有效性, 仲恩進行了一項隨機、雙盲/安慰劑對照的 II 期臨床試驗 (NCT02540655)。 在此試驗中，Stemchymal®累積了大量產品安全性的証據。同時，Stemchymal®亦表現具有延緩疾病惡化速度的潛力。相較於安慰組，Stemchymal®治療組中有更多的受試者在SARA評分中表現出進步的效果。
The safety and efficacy of Stemchymal® for the treatment of PolyQ SCAs was further investigated in a phase II trial, which was randomized, double-blind and placebo controlled. Stemchymal® showed good safety evidence in this phase II trial. Stemchymal® also showed potential therapeutical benefits by slowing down the disease progression in targeted patient group. More patients in the treatment group showed improvement compared with that in the placebo group.
除台灣之外，Stemchymal®治療PolyQ SCAs的開發亦在日本、美國及韓國進入II期臨床階段或正準備申請。
Stemchymal® treatment for PolyQ SCAs is also in clinical stage in the US (phase II), Japan (phase II) and South Korea (preparing for phase II IND submission).
值得關注的是，Stemchymal®應用於脊髓小腦性共濟失調治療在2015年與2018年分別拿到美國與日本的孤兒藥認定，這讓藥物在開發上可以享有法規單位的輔導、縮短藥物臨床試驗申請審查的時間、獲得臨床研究經費補助和稅率優惠等。最重要的是，孤兒藥的認定將有助於仲恩在未來取得藥證上市後有市場獨賣期，協助公司穩定市場和獲利的機會。
In December 2015, Steminent received US FDA Orphan Drug Designation for Stemchymal® in the treatment of PolyQ SCAs.
