◎アルコール代謝異常の新規薬　　頻脈とアセトアルデヒド低下

PR32621 ☆共ＪＢＮ　外１１７５（産業、医療）（０８・１１・１４） 【産業担当デスク殿】３２６２１ ◎アルコール代謝異常の新規薬 　　頻脈とアセトアルデヒド低下 【ノバト（米カリフォルニア州）１４日ＰＲＮ＝共同ＪＢＮ】ラプター・ファーマシューティカルズ（以下ラプター、ＯＴＣブレティンボード：ＲＰＴＰ）は１４日、同社のコンビビア（Ｃｏｎｖｉｖｉａ、商標）開発プログラムにおける初期段階の成果として、ＡＬＤＨ２を欠損しているアルコール不耐性の被験者に４−メチルピラゾール（４−ＭＰ）を経口投与した第２ａ相臨床試験で好成績を得たと発表した。コンビビアはラプター社の医療用医薬品の経口４−ＭＰ製剤であり、アルコール摂取後のＡＬＤＨ２欠損者において体内でのアセトアルデヒド暴露および関連症状を軽減する効果がある。コンビビアの有効成分で、今回の第２ａ相臨床試験に使われた４−ＭＰは、その他の適用では注射用製剤として販売されているが、ＡＬＤＨ２欠損者におけるアルコール暴露に関連したアセトアルデヒド毒性の治療薬としては開発途中にある。 （ロゴ：　http://www.newscom.com/cgi-bin/prnh/20071022/NYM074LOGO） 　同臨床試験は盲検化、被験者内対照、単回投与、用量漸増試験で、過去にアルコール暴露に伴って先天性アルコール代謝異常の症状を呈したことがある日系人３２人が参加してハワイで実施された。試験参加時に被験者は、アルコール脱水素酵素（ＡＤＨ）およびＡＬＤＨ２（アルデヒド脱水素酵素２型）の遺伝子型診断も受けた。試験の目的は、アルコールを摂取するＡＬＤＨ２欠損被験者において、アセトアルデヒド毒性による症状の治療薬として可能性がある４−ＭＰの安全性と有効性を検討することであった。試験ではまた、最適有効用量および投与回数、用量範囲の設定のための情報収集も目的とした。 　試験の結果、コンビビアの有効成分は、すべての試験用量で飲酒をするＡＬＤＨ２欠損者が多く経験する症状である心臓の動悸（頻脈）を有意に抑制した。また、試験からは、ある特定の肝ＡＤＨおよびＡＬＤＨ２酵素の遺伝的変異を有する被験者サブグループにおいて、アセトアルデヒドのピーク値および総暴露量が４−ＭＰによって有意に低下することが示された。このサブグループは、成人ＡＬＤＨ２欠損者人口の約３分の１を占める。 　ラプター社の臨床部門社長であるテッド・デーリー氏は「コンビビアの第２ａ相臨床試験の成績を得てわれわれは自信を深めた。現在、ＡＬＤＨ２欠損の治療薬として承認された薬剤はなく、発がん物質として知られるアセトアルデヒドへの暴露が軽減され、飲酒による不快な反応が緩和されれば、この障害をもつ人々に恩恵がもたらされる可能性は高い。われわれはアジア諸国で臨床的および商業的事業パートナーを探し、この製品候補の開発を継続していく計画をもっている」と語った。 　▽ＡＬＤＨ２欠損について 　ＡＬＤＨ２欠損は、「アジアン・フラッシング・シンドローム（アジア人顔面紅潮症候群）」と呼ばれることもあり、東アジア人口の４０〜５０％に認められる遺伝性代謝障害で、肝臓のアルデヒド脱水酵素（ＡＬＤＨ２）の働きが障害される。ＡＬＤＨ２欠損者がアルコール飲料を飲むと発がん性のアルコール中間代謝物質であるアセトアルデヒドが血中や組織に蓄積される。公表されているレトロスペクティブ（後ろ向き）試験の結果からは、飲酒習慣のあるＡＬＤＨ２欠損者には、消化管がん、肝臓がん、遅発性アルツハイマー病、およびその他の重篤な健康障害と有意な関連があることが認められている。長期にわたる健康リスクに加えて、アセトアルデヒド値の上昇は、顔面紅潮、頻脈（心拍数の増加）、頭痛、吐き気、めまいなどの症状を引き起こす。ＡＬＤＨ２欠損者は、飲酒による不快な反応に苦しみ、長期の健康リスクに直面しているにもかかわらずアルコールを常飲する割合が高い。 　▽ラプター・ファーマシューティカルズ（Raptor Pharmaceuticals Corp.）について 　ラプター・ファーマシューティカルズは、高度に専門化したドラッグターゲティング技術と製剤化経験を応用して既存の治療薬の改善し、患者に新たな治療オプションを迅速に提供することに特化して事業を展開している。ターゲットとしているのは十分な治療を受けていない患者層で、この領域で最も貢献できる可能性があると考えている。ラプターは現在、アルデヒド脱水素酵素（ＡＬＤＨ２）に欠損がある患者、腎障害性シスチン蓄積症患者、および非アルコール性脂肪性肝炎（ＮＡＳＨ）患者を対象とする臨床試験を実施している。 　ラプターの前臨床段階にある開発プログラムには、がん、神経変性疾患、感染症を対象に開発された新規の遺伝子組み換え候補薬、ヒト受容体関連タンパク質（ＲＡＰ）およびこれに関連するタンパク質に由来するドラッグターゲティングの応用などがある。 　ラプター社に関する情報はwww.raptorpharma.com.を参照。 (了) ▽問い合わせ先 Investors: Sara Ephraim, +1-646-536-7002, sephraim@theruthgroup.com Media: Janine McCargo, +1-646-536-7033, jmccargo@theruthgroup.com both of The Ruth Group for Raptor Pharmaceuticals Corp. Photo:  NewsCom:  http://www.newscom.com/cgi-bin/prnh/20071022/NYM074LOGO

Raptor Pharmaceuticals Corp. Announces Positive Phase IIa Clinical Study Results for Convivia(TM) Program

PR32621 NOVATO, Calif., Nov. 14 /PRN=KYODO JBN/ --     Reduction in Tachycardia and Blood Acetaldehyde Levels in Subset of              Subjects with Inborn Error of Alcohol Metabolism     Raptor Pharmaceuticals Corp. ("Raptor" or the "Company") (OTC Bulletin Board: RPTP), today announced positive results in its Phase IIa study of oral 4-methylpyrazole ("4-MP") in subjects with ALDH2 deficiency, or ethanol intolerance, as the initial development stage of its Convivia(TM) program.   Convivia(TM) is Raptor's proprietary oral formulation of 4-MP designed to reduce systemic acetaldehyde exposure and related symptoms in ALDH2 deficient persons following alcohol consumption. 4-MP, the active ingredient in Convivia(TM) and used in this Phase IIa study, is marketed in an injectible formulation for other indications, but is investigational for treatment of acetaldehyde toxicity associated with ethanol exposure in ALDH2 deficient subjects.     (Logo:  http://www.newscom.com/cgi-bin/prnh/20071022/NYM074LOGO)     Conducted in Hawaii, the blinded, intra-subject controlled, single dose, dose escalation study enrolled 32 subjects of Japanese descent with a history of symptoms of inborn altered ethanol metabolism with concomitant ethanol exposure. At the time of enrollment, study subjects also submitted to alcohol dehydrogenase ("ADH") and aldehyde dehydrogenase ("ALDH2") genotyping. The objectives of the study were to investigate the safety and efficacy of 4-MP as a potential treatment of symptoms resulting from acetaldehyde toxicity in ALDH2 deficient subjects who drink alcohol. The trial also sought to provide information leading to the most efficacious dose and dosage timing range.     The study results demonstrated that the active ingredient in Convivia(TM) significantly reduced heart palpitations (tachycardia), which are commonly experienced by ALDH2 deficient people who drink, at all dose levels tested.   The study also found that the 4-MP significantly reduced peak acetaldehyde levels and total acetaldehyde exposure in a subset of the study participants who possess specific genetic variants of the liver ADH and ALDH2 enzymes. This subset represents approximately one-third of the ALDH2 deficient adult population.     Ted Daley, President of Raptor's Clinical Division, stated, "We are encouraged by these results from our Phase IIa study for Convivia(TM). Currently there are no approved treatments for ALDH2 deficiency, and people with this disorder could potentially benefit by lessening their exposure to acetaldehyde, a known carcinogen, and mitigating the unpleasant reactions to drinking.  We plan to seek partners with clinical and commercial operations in Asian countries, to continue the development of this product candidate."     About ALDH2 Deficiency     ALDH2 deficiency, sometimes referred to as "Asian flushing syndrome," is an inherited metabolic disorder affecting 40% to 50% of East Asian populations, impairing the activity of the liver enzyme aldehyde dehydrogenase ("ALDH2"). When people with ALDH2 deficiency drink alcoholic beverages, there is an accumulation of acetaldehyde, a carcinogenic intermediate in the metabolism of ethanol, in blood and tissues.  Published retrospective studies have observed a significant correlation between recurrent drinkers with ALDH2 deficiency and an increase in risk for digestive tract cancers, liver diseases, late-onset Alzheimer's disease and other serious health disorders.  In addition to the long-term health risks, elevated acetaldehyde levels produce acute symptoms, including facial flushing, tachycardia (rapid heart rate), headache, nausea and dizziness. Although ALDH2 deficient people suffer from unpleasant reactions and face long-term health risks, a substantial proportion of them are recurring drinkers of alcoholic beverages.       About Raptor Pharmaceuticals Corp.     Raptor Pharmaceuticals Corp. ("Raptor") is dedicated to speeding the delivery of new treatment options to patients by working to improve existing therapeutics through the application of highly specialized drug targeting platforms and formulation expertise. We focus on underserved patient populations where we can have the greatest potential impact. Raptor is currently running clinical trials in patients with aldehyde dehydrogenase ("ALDH2") deficiency, nephropathic cystinosis and non-alcoholic steatohepatitis ("NASH").     Raptor's preclinical programs are based upon bioengineered novel drug candidates and drug-targeting platforms derived from the human receptor-associated protein ("RAP") and related proteins to that are designed to target cancer, neurodegenerative disorders and infectious diseases.     For additional information, please visit www.raptorpharma.com.     FORWARD LOOKING STATEMENTS     This document contains forward-looking statements as that term is defined in the Private Securities Litigation Reform Act of 1995. These statements relate to future events or our future results of operation or future financial performance, including, but not limited to the following statements:  Raptor's ability to obtain Asian partners to further develop Convivia(TM); Raptor's ability to manufacture clinical scale quantities of its proprietary Convivia(TM) formulation; Convivia's(TM) ability to benefit ALDH2 deficient individuals by lessening their exposure to acetaldehyde and mitigating their unpleasant reactions to drinking; the ability of Convivia(TM) to be successfully developed into a marketable treatment; and Raptor's ability to successfully develop any of its other clinical and preclinical products. These statements are only predictions and involve known and unknown risks, uncertainties and other factors, which may cause our actual results to be materially different from these forward-looking statements. Factors which may significantly change or prevent our forward looking statements from fruition include that we may be unsuccessful in developing any products or acquiring products; that our technology may not be validated as we progress further and our methods may not be accepted by the scientific community; that we are unable to retain or attract key employees whose knowledge is essential to the development of our products; that unforeseen scientific difficulties develop with our process; that our patents are not sufficient to protect essential aspects of our technology; that competitors may invent better technology; that our products may not work as well as hoped or worse, that our products may harm recipients; and that we may not be able to raise sufficient funds for development or working capital when we require it. As well, our products may never develop into useful products and even if they do, they may not be approved for sale to the public. We caution readers not to place undue reliance on any such forward-looking statements, which speak only as of the date they were made. Certain of these risks, uncertainties, and other factors are described in greater detail in our filings from time to time with the Securities and Exchange Commission ("SEC"), which we strongly urge you to read and consider, including our Registration Statement on Form S-1, as amended, that was declared effective on August 7, 2008; and our annual report on Form 10-K filed with the SEC on October 30, 2008, all of which are available free of charge on the SEC's web site at http://www.sec.gov. Subsequent written and oral forward-looking statements attributable to us or to persons acting on our behalf are expressly qualified in their entirety by the cautionary statements set forth in our reports filed with the SEC. We expressly disclaim any intent or obligation to update any forward-looking statements.     For more information, please contact:     The Ruth Group     Sara Ephraim (investors)            Janine McCargo (media)     (646) 536-7002                      (646) 536-7033     sephraim@theruthgroup.com           jmccargo@theruthgroup.com SOURCE: Raptor Pharmaceuticals Corp.     CONTACT:  Investors:  Sara Ephraim,               +1-646-536-7002,               sephraim@theruthgroup.com;               Media: Janine McCargo,               +1-646-536-7033,               jmccargo@theruthgroup.com,                         both of The Ruth Group for Raptor Pharmaceuticals Corp.     Photo:  NewsCom:  http://www.newscom.com/cgi-bin/prnh/20071022/NYM074LOGO