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窪田製薬HD Research Memo(3):スターガルト病治療薬、PBOSの開発が順調に進む(1)


■主要開発パイプラインの概要と開発動向

1. 開発パイプラインの進捗状況
窪田製薬ホールディングス<4596>の現在の開発パイプラインは、医薬品でエミクススタト(適応症:スターガルト病、増殖糖尿病網膜症)、ヒトロドプシン※を用いた遺伝子治療(適応症:網膜色素変性)のほか、白内障及び老視を適応症とした低分子化合物、糖尿病黄斑浮腫やウェット型加齢黄斑変性を適応症とした低分子化合物がある。一方、医療デバイスでは在宅・遠隔医療モニタリング機器となるPBOSの開発を進めている。

※ヒトの網膜の杆体細胞を構成するタンパク質の一種で、光受容体(光信号を電気信号に変えて脳に伝達する)の機能を果たす。


2018年12月期第3四半期(2018年7月-9月)は各パイプラインにおける大きな進捗はなかったものの、2018年11月にスターガルト病を適応症としたエミクススタトの臨床第3相試験が開始されたほか、PBOSのプロトタイプ機の臨床試験が同年10月に終了し、主要項目で良好な結果が得られたことを発表している。

2. エミクススタト(スターガルト病)
スターガルト病は遺伝性の若年性黄斑変性で有効な治療法が確立していない稀少疾患の1つである。8千人から1万人に1人の割合で発症し、患者数は日米欧で15万人弱、米国だけで見ると3.2~4万人と推計されている※。小児期から青年期における視力低下や色覚障害等が主な症状として挙げられ、大半の患者が視力0.1以下に低下すると言われている。

※Market Scope,「Retinal Pharma & Biologics Market」「UN World Population Prospects 2015」をもとに、同社が推計。


発症原因は、網膜内にあるABCA4遺伝子の突然変異によるものと考えられている。ABCA4遺伝子は光を感じる働きを司る「視覚サイクル」によって生じる有害なリポフスチン(以下、A2E)を処理する役割を果たすが、本遺伝子が突然変異により本来の役割を果たさなくなることで網膜内にA2Eが蓄積し、視力低下が徐々に進行していくメカニズムとなる。

エミクススタトは動物モデルを用いた非臨床試験において、このA2Eの蓄積を抑制する効果が確認されている。エミクススタトは「視覚サイクル」において重要な役割を果たすRPE65と呼ばれる酵素を選択的に阻害するため、視覚サイクルによって生じる老廃物を減らす作用があり、症状の進行を抑制する効果が期待される。

2017年1月より実施した臨床第2a相試験(22症例)ではエミクススタト投与1ヶ月後に、網膜電図を用いて点滅光に対する網膜の電気的応答の変化を検証した。杆体の反応は、網膜電図ではb波で示される。エミクススタトは視覚サイクルにおいて重要な役割を果たす酵素RPE65を阻害して杆体を休ませることで、視覚サイクルを抑制する働きが確認されている。このことから、本試験ではスターガルト病患者に対して、杆体b波の振幅が投与1ヶ月後にどれくらいの割合で抑制されるかを主要項目に設定して実施した。その結果、用量依存的で最大90%を超える抑制効果が見られた。また、投与用量における安全性及び忍容性が確認され、主要評価項目を達成した。

同社ではこの結果を受けて、臨床第3相試験を2018年11月より開始している。本臨床試験ではプラセボとの二重盲検比較試験を行い、1日1回、10mgの経口投与を24ヶ月間実施する。欧米の約10ヶ国、約30施設で合計約160名の被験者登録を見込んでいる。主要評価項目は、プラセボ群に対する黄斑部の萎縮進行の抑制効果を検証するというもの。また、副次的評価項目として最良矯正視力のスコアや読速度などの視機能の変化も見る。米国では2017年にFDAからオーファンドラッグ※認定を受けている。なお、競合薬の開発状況としては、サノフィ(フランス)が臨床第1/2相試験を行っている段階にある。

(執筆:フィスコ客員アナリスト 佐藤 譲)



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    Function: _error_handler

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    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
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    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/d064ec4523cd2f49c67136b7b84705846d19c90b_0.file.side.tpl.php
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    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
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    Function: callBlock

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    Line: 184
    Function: callBlock

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 186
    Function: process

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
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    Function: process

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    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
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    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 386
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
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    Function: _subTemplateRender

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    Function: content_675a781dcbf339_49719938

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_templatebase.php
    Line: 238
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_templatebase.php
    Line: 116
    Function: _execute

    File: /www/wwwroot/homev2.kingsoft.jp/application/libraries/SmartyLibrary.php
    Line: 45
    Function: fetch

    File: /www/wwwroot/homev2.kingsoft.jp/application/controllers/ArticleController.php
    Line: 32
    Function: view

    File: /www/wwwroot/homev2.kingsoft.jp/public/index.php
    Line: 292
    Function: require_once

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    Filename: smarty/49292b3df7e5bd60f7381ff16c5ca4532cf9476f_0.file.card.tpl.php

    Line Number: 24

    Backtrace:

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/49292b3df7e5bd60f7381ff16c5ca4532cf9476f_0.file.card.tpl.php
    Line: 24
    Function: _error_handler

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b3d136f97_11902452

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 384
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/08d1cc69876d91563afb9c1f4d21cc8b7b96caa4_0.file.tips.tpl.php
    Line: 41
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b3d14aa11_83151422

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 386
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/d064ec4523cd2f49c67136b7b84705846d19c90b_0.file.side.tpl.php
    Line: 43
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b47775ef5_14228348

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 386
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/597cefa22c7600eaa32b117569a9685c70819274_0.file.show.tpl.php
    Line: 416
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 248
    Function: callBlock

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 184
    Function: callBlock

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 186
    Function: process

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 156
    Function: process

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/fbdaa42e51518f8881faeabdc1199f6dd175d1ce_0.file.base_index_layout.tpl.php
    Line: 88
    Function: instanceBlock

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b3cb92fa0_94546305

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 386
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 116
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/597cefa22c7600eaa32b117569a9685c70819274_0.file.show.tpl.php
    Line: 71
    Function: endChild

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_675a781dcbf339_49719938

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_templatebase.php
    Line: 238
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_templatebase.php
    Line: 116
    Function: _execute

    File: /www/wwwroot/homev2.kingsoft.jp/application/libraries/SmartyLibrary.php
    Line: 45
    Function: fetch

    File: /www/wwwroot/homev2.kingsoft.jp/application/controllers/ArticleController.php
    Line: 32
    Function: view

    File: /www/wwwroot/homev2.kingsoft.jp/public/index.php
    Line: 292
    Function: require_once

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    Severity: Notice

    Message: Trying to access array offset on value of type null

    Filename: smarty/49292b3df7e5bd60f7381ff16c5ca4532cf9476f_0.file.card.tpl.php

    Line Number: 29

    Backtrace:

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/49292b3df7e5bd60f7381ff16c5ca4532cf9476f_0.file.card.tpl.php
    Line: 29
    Function: _error_handler

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b3d136f97_11902452

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 384
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/08d1cc69876d91563afb9c1f4d21cc8b7b96caa4_0.file.tips.tpl.php
    Line: 41
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b3d14aa11_83151422

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 386
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/d064ec4523cd2f49c67136b7b84705846d19c90b_0.file.side.tpl.php
    Line: 43
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b47775ef5_14228348

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 386
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/597cefa22c7600eaa32b117569a9685c70819274_0.file.show.tpl.php
    Line: 416
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 248
    Function: callBlock

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 184
    Function: callBlock

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 186
    Function: process

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 156
    Function: process

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/fbdaa42e51518f8881faeabdc1199f6dd175d1ce_0.file.base_index_layout.tpl.php
    Line: 88
    Function: instanceBlock

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b3cb92fa0_94546305

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 386
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 116
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/597cefa22c7600eaa32b117569a9685c70819274_0.file.show.tpl.php
    Line: 71
    Function: endChild

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_675a781dcbf339_49719938

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_templatebase.php
    Line: 238
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_templatebase.php
    Line: 116
    Function: _execute

    File: /www/wwwroot/homev2.kingsoft.jp/application/libraries/SmartyLibrary.php
    Line: 45
    Function: fetch

    File: /www/wwwroot/homev2.kingsoft.jp/application/controllers/ArticleController.php
    Line: 32
    Function: view

    File: /www/wwwroot/homev2.kingsoft.jp/public/index.php
    Line: 292
    Function: require_once

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    Line Number: 41

    Backtrace:

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/08d1cc69876d91563afb9c1f4d21cc8b7b96caa4_0.file.tips.tpl.php
    Line: 41
    Function: _error_handler

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b3d14aa11_83151422

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 386
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/d064ec4523cd2f49c67136b7b84705846d19c90b_0.file.side.tpl.php
    Line: 43
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b47775ef5_14228348

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 386
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/597cefa22c7600eaa32b117569a9685c70819274_0.file.show.tpl.php
    Line: 416
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 248
    Function: callBlock

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 184
    Function: callBlock

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 186
    Function: process

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 156
    Function: process

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/fbdaa42e51518f8881faeabdc1199f6dd175d1ce_0.file.base_index_layout.tpl.php
    Line: 88
    Function: instanceBlock

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b3cb92fa0_94546305

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 386
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 116
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/597cefa22c7600eaa32b117569a9685c70819274_0.file.show.tpl.php
    Line: 71
    Function: endChild

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_675a781dcbf339_49719938

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_templatebase.php
    Line: 238
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_templatebase.php
    Line: 116
    Function: _execute

    File: /www/wwwroot/homev2.kingsoft.jp/application/libraries/SmartyLibrary.php
    Line: 45
    Function: fetch

    File: /www/wwwroot/homev2.kingsoft.jp/application/controllers/ArticleController.php
    Line: 32
    Function: view

    File: /www/wwwroot/homev2.kingsoft.jp/public/index.php
    Line: 292
    Function: require_once

    A PHP Error was encountered

    Severity: Notice

    Message: Trying to access array offset on value of type null

    Filename: smarty/49292b3df7e5bd60f7381ff16c5ca4532cf9476f_0.file.card.tpl.php

    Line Number: 24

    Backtrace:

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    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
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    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
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    Line Number: 29

    Backtrace:

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    Line: 123
    Function: content_66f26b3d136f97_11902452

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 384
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/08d1cc69876d91563afb9c1f4d21cc8b7b96caa4_0.file.tips.tpl.php
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    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b3d14aa11_83151422

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 386
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/d064ec4523cd2f49c67136b7b84705846d19c90b_0.file.side.tpl.php
    Line: 43
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b47775ef5_14228348

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
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    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/597cefa22c7600eaa32b117569a9685c70819274_0.file.show.tpl.php
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    Function: callBlock

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    Function: callBlock

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
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    Function: process

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 156
    Function: process

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/fbdaa42e51518f8881faeabdc1199f6dd175d1ce_0.file.base_index_layout.tpl.php
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    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b3cb92fa0_94546305

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
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    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
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    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
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    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
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    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/597cefa22c7600eaa32b117569a9685c70819274_0.file.show.tpl.php
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    Line: 123
    Function: content_675a781dcbf339_49719938

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
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    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_templatebase.php
    Line: 238
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_templatebase.php
    Line: 116
    Function: _execute

    File: /www/wwwroot/homev2.kingsoft.jp/application/libraries/SmartyLibrary.php
    Line: 45
    Function: fetch

    File: /www/wwwroot/homev2.kingsoft.jp/application/controllers/ArticleController.php
    Line: 32
    Function: view

    File: /www/wwwroot/homev2.kingsoft.jp/public/index.php
    Line: 292
    Function: require_once

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