Daiichi Sankyo第一三共株式会社 fetched new indications for Indocyanine green (Diagnogreen): Evaluation of blood circulation in vascular and tissues

Daiichi Sankyo Obtains Approval for Additional Indication and Dosage for DiagnogreenⓇ for Injection 25 mg in Japan Tokyo, Japan (July 2, 2018) – Daiichi Sankyo Company, Limited (hereinafter, Daiichi Sankyo) today announced that it has obtained approval in Japan for an additional indication and dosage for Diagnogreen® for injection 25 mg (indocyanine green; hereinafter, ICG) for evaluation of blood circulation in vascular and tissues (hereinafter, this indication). The Review Committee for Unapproved or Off-label Use of Drugs with High Medical Needs*1 recommended that a public knowledge-based application*2 should be made concerning this indication, and the acceptability of a public knowledge-based application was determined by the First Committee on New Drugs of the Pharmaceutical Affairs and Food Sanitation Council on January 26, 2018. Based on this, Daiichi Sankyo submitted a supplemental new drug application for an additional indication and dosage on February 22, 2018. This indication is already approved in Europe (including UK and Germany) and the drug is widely used in Japan as a means for mainly visual and real-time confirmation of blood circulation in various fields of surgery (vascular, cardiac, gastrointestinal, plastic, etc.) Daiichi Sankyo is committed to making unapproved and off-label drugs with high medical needs available to patients who are waiting for them to be approved.

*1 Review Committee for Unapproved or Off-label Use of Drugs with High Medical Needs A committee established under the sponsorship of the MHLW with the aim of promoting pharmaceutical companies to develop unapproved or off-labeled drugs with indications approved in foreign countries but not in Japan.

*2 Public knowledge-based applications Application for a drug commonly known to be medically and pharmaceutically safe and with proven efficacy for which clinical trials can be partly or entirely omitted.

「ジアグノグリーンⓇ注射用25mg」の効能･効果および用法･用量追加に係る承認取得のお知らせ2018年7月2日 会社名 第一三共株式会社 代表者 代表取締役社長　眞鍋　淳（コード番号4568東証第１部） 問合せ先 執行役員ｺｰﾎﾟﾚｰﾄｺﾐｭﾆｹｰｼｮﾝ部長 小川　晃司 TEL　報道関係者の皆様　03-6225-1126 株式市場関係者の皆様　03-6225-1125第一三共株式会社（本社：東京都中央区、以下「当社」）は、本日、ジアグノグリーンⓇ注射用25mg（一般名：インドシアニングリーン、以下「本剤」）の「血管及び組織の血流評価」(以下「本適応症」)の効能･効果および用法･用量追加に係る承認を取得しましたのでお知らせいたします。本剤は、医療上の必要性の高い未承認薬･適応外薬検討会議*1で本適応症に関する公知申請*2を行うことが適当と判断され、2018年1月26日に開催された薬事・食品衛生審議会医薬品第一部会において公知申請を行うことが了承されました。これらを受け当社は2018年2月22日に効能・効果及び用法・用量追加に係る医薬品製造販売承認事項一部変更承認申請を行いました。本適応症は、既に欧州（英国およびドイツ等）で承認されており、国内においても各外科領域(血管、心臓、消化器、形成など)で、主に手術時に視覚的、またリアルタイムに血流を確認する手段として用いられています。当社は、引き続き医療上の必要性の高い未承認薬・適応外薬の解消に取り組み、医療に貢献してまいります。以 上

*1医療上の必要性の高い未承認薬･適応外薬検討会議について厚生労働省が主催し、欧米等では使用が認められているが、国内では承認されていない医薬品や適応について、製薬企業による未承認薬・適応外薬の開発を促進することを目的として設置された会議

*2公知申請について 医薬品（効能・効果追加等）の承認申請に関して、その医薬品の有効性や安全性が医学薬学上公知であるとして、臨床試験の全部又は一部を新たに実施することなく行う申請

2 optical methods of care have emerged that are able to obtain high spatial resolution images with easily implemented instrumentation: indocyanine green (ICG) angiography and laser speckle contrast imaging (LSCI). Neurosurgery 71:1023–1031, 2012 

Indocyanine green  

更勝保肝! silibinin水飛薊賓抑制肺癌腦轉移並延長病人存活期(15.5M vs 4 M): 關鍵點reactive astrocytes (active STAT3)

無論哪種癌症的致命腦轉移，都有救了！ 肺癌康復圈 腫瘤並不可怕，可怕的是轉移，這句話大家一定耳熟能詳。而腦轉移更是預後顯著惡化的先兆！據統計，原發性腫瘤有10％至40％的概率會發生腦轉移，目前針對腫瘤腦轉移的方案主要是手術和放療，但收效甚微。 雖然近年來在靶向治療或免疫治療方面也曾出現過一些替代方案，但即便是在最佳狀況下，也僅有20％的患者能夠因此獲益。近日，研究小組在Nature Medicine雜誌上發表的一項研究表明，對腦轉移的病人使用silibinin可以減少病變，且不會造成任何不良影響，這種化合物有望成為治療腦轉移的有效且安全的替代方案。

Silibinin是何方神聖？早在2015年的美國癌症研究協會（AACR）年會上，就出現過它的大名——silibinin，中文名水飛薊賓，是一種存在於牛奶薊種子內的非毒性，潛在的化學預防劑。

Silibinin停止大腸腫瘤幹細胞生長 當時來自科羅拉多大學的學者展示了最新的研究結果關於silibinin能減慢結直腸癌幹細胞生長的能力。silibinin治療後採樣的腫瘤幹細胞重新注入到新模型上，細胞未能發展成具有同樣侵襲性的腫瘤，即使在沒有再服用水飛薊賓的情況下。在silibinin餵養的小鼠腫瘤內，腫瘤幹細胞數目很少，腫瘤體積較小，代謝水準較低，並表現出新的血管生長水準下降。 更重要的是，silibinin餵養的小鼠的腫瘤幹細胞失去了分裂繁殖的能力。研究人員表示具體的分子機制的發現還需要一定的研究，確認silibinin在癌症的預防和或治療的人體臨床實驗也在計畫之中。研究者嘗試在小鼠中把這種STAT3基因從反應性星形膠質細胞中消除，並結合silibinin，發現其腦轉移得到了顯著改善。而後，研究者進行了18名肺癌腦轉移患者的佇列研究，結果顯示：75％的患者在腦轉移水準呈陽性反應。 其中3名患者（20％）顯示總反應，10名（55％）顯示部分反應。平均存活率為15.5個月，而對照組僅為4個月。 對於任何類型的腦轉移，這種治療方法都可以發揮效力，而無論其原發腫瘤是什麼。但是儘管取得了積極的成果，但還是必須對這種化合物進行進一步的試驗。並且值得關注的是，這是史上第一個針對腦轉移的靶向治療方法，可以說是腦轉移治療的里程碑，由它帶來的積極意義也勢必將不可估量。

Silibinin (INN), also known as silybin (both from Silybum, the generic name of the plant from which it is extracted), is the major active constituent of silymarin, a standardized extract of the milk thistle seeds, containing a mixture of flavonolignans consisting of silibinin, isosilibinin, silicristin, silidianin, and others.

 

A new therapy proves effective against brain metastasis  June 11, 2018, The National Centre for Cancer Research. A study published in Nature Medicine by a team led by Manuel Valiente, head of the Brain Metastasis Group at the Spanish National Cancer Research Centre (CNIO), shows that the administration of silibinin in patients with brain metastasis reduces lesions without causing any adverse effects. This preliminary trial provides proof of concept that this compound could be a new effective and safe alternative to treat brain metastasis. "We have demonstrated, taking into account all the considerations relevant to a compassionate use trial such as ours, that we can successfully treat brain metastasis," says Valiente. "This treatment could also be valid for any type of brain metastasis, regardless of the primary tumour that generated it," he added. It is estimated that between 10 percent and 40 percent of primary tumours generate metastasis in the brain, a situation that worsens patient prognosis considerably. Few advances have been made in terms of treatment; currently, brain metastasis is still being treated with surgery and/or radiotherapy. In recent years, some alternatives have appeared in terms of targeted therapies or immunotherapy, but the percentage of patients who might benefit from these therapies is just 20 percent in the best-case scenario.

The tumour microenvironment as a critical factor in metastasis The role of the cellular context (microenvironment) in which a tumour develops is becoming increasingly important, not only with a view to understanding how cancer cells grow, but also to know how to attack them. In the brain, an inhospitable environment for any foreign element, the role of the microenvironment is relevant and understudied. Valiente and his group have been studying this brain microenvironment for years, focusing in particular on two elements: One, a population of cells known as astrocytes, which respond to damage by entering into a reactive state and which are associated with metastasis. Two, the STAT3 gene, which research has established is involved with brain metastasis. As shown in this research, the activation of STAT3 is significant in a subpopulation of reactive astrocytes that are key to establishing a pro-metastatic environment. When this gene is eliminated from the reactive astrocytes, the viability of brain metastasis is compromised. With this information on the table, Valiente's research group used a novel drug screening strategy developed by them called METPlatform. This tool is capable of analysing the relationship between hundreds of compounds and the metastatic cells found in the target organ simultaneously; in this case, in the brain. "This strategy allows us to assess experimental drugs as well as those that are already in use for other types of pathologies that might or might not be linked to cancer. We believe that by using METPlatform we can be more efficient in developing new therapeutic options, since we can study the metastatic cell growing in the organ being colonised," explained Valiente. One of the compounds tested in this preparation was silibinin, whose anti-tumour potential had previously been established by Joaquim Bosch, Head of the Lung Cancer Unit at Catalonia's Cancer Institute (ICO) in Girona, and co-author of this study. "In 2016, we reported positive brain responses in two patients with no other treatment options who received silibinin, but we did not know how it worked. Thanks to this research, led by Valiente's group, we now understand how it acts at the level of the brain," said Bosch. A new therapeutic concept with encouraging results Following the good results obtained by blocking STAT3 with silibinin in mice, the authors established a cohort of 18 patients with lung cancer and brain metastasis for whom compassionate use of this drug was granted in combination with standard treatment. 75 percent of the patients reacted positively at the level of brain metastasis. Three patients (20 percent) displayed a total response, and 10 (55 percent) a partial response. Average survival rate was 15.5 months, whereas in the control group (composed of patients treated for this disease in the same institution during 2015-2016) it was four months. "Our treatment mainly targets the brain environment that has been altered by metastasis. This is a new therapeutic concept," said Valiente. "We are also attacking an alteration that is only seen when there is brain metastasis, and which is necessary for its viability," he added. "We have explored whether therapies targeting organ-specific survival mechanisms could be a novel approach to treat brain metastasis," explains Neibla Priego, first author of the study. In spite of the positive results, further trials must be conducted with this compound before it can be incorporated into clinical practice. Researchers have been trying to launch such trials for months, but so far, they have not been able to secure the funding they need in order to do so. "This present research describes the first targeted therapy for brain metastasis that acts by attacking its tumour microenvironment. However, more data are needed before it can be incorporated into clinical practice. The 18 patients treated so far indicate that it would be feasible to administer this treatment and that it could be very relevant at a clinical level. Clinical trials, with silibinin or with drugs that act against this target, are crucial if we wish to make this new therapeutic option available to patients," concluded Bosch, head of the clinical study, and Valiente, research director. Patients with brain metastasis have traditionally been excluded from clinical trials because of their poor prognosis. "It now appears that there is a move toward not excluding them given their growing importance in clinical practice. In this regard, we hope that with METPlatform we will be able to help build confidence so that new drugs can be evaluated on these patients," adds Valiente.

 

STAT3 labels a subpopulation of reactive astrocytes required for brain metastasis

Nature Medicine (2018) |The brain microenvironment imposes a particularly intense selective pressure on metastasis-initiating cells, but successful metastases bypass this control through mechanisms that are poorly understood. Reactive astrocytes are key components of this microenvironment that confine brain metastasis without infiltrating the lesion. Here, we describe that brain metastatic cells induce and maintain the co-option of a pro-metastatic program driven by signal transducer and activator of transcription 3 (STAT3) in a subpopulation of reactive astrocytes surrounding metastatic lesions. These reactive astrocytes benefit metastatic cells by their modulatory effect on the innate and acquired immune system. In patients, active STAT3 in reactive astrocytes correlates with reduced survival from diagnosis of intracranial metastases. Blocking STAT3 signaling in reactive astrocytes reduces experimental brain metastasis from different primary tumor sources, even at advanced stages of colonization. We also show that a safe and orally bioavailable treatment that inhibits STAT3 exhibits significant antitumor effects in patients with advanced systemic disease that included brain metastasis. Responses to this therapy were notable in the central nervous system, where several complete responses were achieved. Given that brain metastasis causes substantial morbidity and mortality, our results identify a novel treatment for increasing survival in patients with secondary brain tumors.

 

 

(エーブィエ バイオファーム) AZとMSDPARP阻害薬リムパーザをコ・プロがん領域の強化狙い 公開日時

2018/06/29アストラゼネカ（AZ）とMSDは6月28日、AZが製造販売するPARP阻害薬リムパーザ（一般名：オラパリブ）について、がん領域の強化を図るグローバルの戦略的提携にもとづくコ・プロモーションを日本でも始めると発表した。７月１日から実施する。同剤は、がん細胞に特異的に細胞死を誘導する作用を持つとされる世界初のPARP阻害薬。日本では2018年1月に「白金系抗悪性腫瘍剤感受性の再発卵巣がんにおける維持療法」で承認され、近く「がん化学療法治療歴のあるBRCA遺伝子変異陽性かつHER2陰性の手術不能または再発乳がん」を効能・効果に追加する承認が見込まれる。このコ・プロは、2017年７月、英AZと米メルクによるオラパリブ（日本製品名：リムパーザ）、開発中のMEK阻害剤セルメチニブ（日本での開発状況非開示）の共同開発・商業化に関する戦略的提携に基づくもの。この中には各々の社が単独で、AZの抗PD-L1抗体デュルバルマブ（日本での予定製品名：イミフィンジ）もしくはメルクの抗PD-1抗体ペムブロリズマブ（日本製品名：キイトルーダ）との併用療法としてオラパリブ、セルメチニブを開発することも盛り込まれている。

 

2018Q1~2 FDA批准17新藥之一: 癌藥止吐: AKYNZEO (palonosetron, a serotonin-3 (5-HT3) receptor antagonist+ fosnetupitant, substance P/neurokinin-1 (NK-1) receptor antagonists)

2018上半年FDA批准的17個新藥匯總及逐個評述 譚九零 藥智網2018年上半年，FDA藥品審評與研究中心（CDER）批准了17個新藥，這些新藥包括新藥申請NDA中的新分子實體（NME）和生物製品許可申請（BLA）。上圖是過去10年中，CDER每年批准的新藥數。2018年上半年CDER批准的新藥包括5個BLA和12個NME。相比於2017年上半年的23個減少了6個，略高於2016上半年和2015上半年。

罕見病/孤兒藥(Rare OR "Orphan" Diseases) 已批准的17個新藥中，8個新藥獲得了孤兒藥資格（O），占CDER批准新藥的47%。罕見病有兩個特徵，其一為患者人數少，美國為少於20萬人的疾病，歐盟屬於5/10000的疾病；其二為危及生命和健康的嚴重疾病。

優先審評（Priority Review）如果CDER確定藥品能夠有潛力對醫療保健做出實質性推動，藥品將獲得優先審評。藥品在6個月內而不是標準的10個月內審評。2018年上半年獲批新藥中有8個被認定為優先審評（P），占17個新藥的47%。 CDER應用多種監管方法加快新藥研發和審批。這些方法除了優先審評還包括：快速通道（Fast Track）、突破性治療認定（Breakthrough）和加速批准（Accelerated Approval）。 治療領域方面，2018年上半年還是比較豐富，抗腫瘤藥明顯減少，僅有2個。整體來說，美國FDA還是各藥企新藥上市的首選，17個新藥有12個藥物都是全球首批，其餘的大多在歐盟首批。

品種評述

01 Lutathera 1月26日，FDA批准了諾華子公司法國Advanced Accelerator Applications 公司Lutathera用於治療影響胰腺或胃腸道的一類癌症，即胃腸胰腺神經內分泌腫瘤（GEP-NETs）。 Lutathera是一種Lu-177標記的生長抑素類似物，屬於新興的肽受體放射性核素療法（PRRT），通過與一種稱為生長激素抑制素受體的細胞結合而起作用，該生長抑素受體可能存在於某些腫瘤上。在與受體結合之後，藥物進入細胞，釋放輻射來損傷腫瘤細胞。在美國和歐盟，Lutathera均被授予孤兒藥地位。歐盟已於2017年10月批准用於治療不可切除或轉移的生長抑素受體陽性胃腸胰腺神經內分泌腫瘤成人患者。這也是放射性藥物首次被FDA批准用於治療GEP-NETs。

02 Biktarvy 2月7日，FDA批准了Gilead公司的Biktarvy，作為每日一次的單片片劑療法，用於治療HIV-1感染。 Biktarvy是一款全新的無助推（unboosted）整合酶鏈轉移抑制劑（INSTI），由bictegravir（50mg）、emtricitabine（200mg）、與tenofovir alafenamide（25mg）三種成分組成。 Biktarvy的療效與安全性在4項正在進行的3期臨床試驗中得到了驗證。試驗1489和1490招募的是初治的HIV-1感染成人患者，而試驗1844與1878則招募了病毒感染在病毒學上得到抑制的成人患者。 在試驗1489中，629名患者以1：1的比例分為兩組,分別接受Biktarvy與abacavir/dolutegravir/lamivudine（600/50/300mg）的治療。在48周後，這兩組患者中，分別有92.4%和93.0%的患者達到了HIV-1 RNA小於每毫升50c的主要終點。而在試驗1490中，645名患者接受的分別是Biktarvy與dolutegravir/FTC/TAF。同樣，兩組達到主要終點的比例接近，分別為89.4%與92.9%。 在試驗1878中，577名在藥物作用下，HIV-1 RNA已經小於每毫升50c的成人患者被1：1分為兩組，一組繼續現有的療法，另一組則切換到Biktarvy的治療。在48周後，兩組中均有1.7%的患者其HIV-1 RNA回到不低於每毫升50c的水準；而根據FDA的演算法，分別有92.1%（Biktarvy組）與88.9%（現有療法組）的患者保持了HIV-1 RNA小於每毫升50c。

03  Symdeko 2月13日，FDA批准了Vertex醫藥公司的Symdeko上市，用於治療12歲及以上的囊性纖維化（cystic fibrosis，CF）患者。SYMDEKO是Vertex獲得FDA批准的第3種針對囊性纖維化根本病因的治療藥物。囊性纖維化是一種罕見的會縮短壽命的遺傳疾病，影響了北美、歐洲和澳大利亞約 75000 名患者，由基因突變導致的 CFTR 蛋白缺陷或缺失引起。兒童必須遺傳到兩個有缺陷的 CFTR 基因——分別來自父母，才會患囊性纖維化。CFTR 基因中有約 2000 個已知的突變，其中一些突變會通過在細胞表面產生不工作或過少的 CFTR 蛋白，它們可以通過基因檢測或基因分型檢測來確定。CFTR 蛋白的功能缺陷或缺失導致許多器官細胞中鹽和水的流入和流出不均衡。在肺中，這會造成異常粘稠的粘液積聚，引起慢性肺部感染和進行性肺損傷，並最終導致死亡。囊性纖維化患者的中位壽命在 20 歲左右。據悉，歐洲藥品管理局（EMA）已經確認了tezacaftor/ivacaftor組合藥物的行銷授權申請（MAA）。公司預計在2018年下半年獲得歐盟批准。

04  Erleada (apalutamide) 2月14日，FDA批准強生Erleada (apalutamide) 上市，用於治療非轉移性（前列腺癌細胞未擴散）去勢抵抗（激素治療後疾病仍進展）的前列腺癌。 Erleada獲得過FDA的優先審評資格，是FDA批准的首個治療非轉移性去勢抵抗前列腺癌的藥物，也是首個憑藉無轉移生存期（metastasis-free survival，MFS）的臨床終點獲批上市的腫瘤新藥。 Erleada的安全性及療效在涉及1207例非轉移性去勢抵抗前列腺癌的隨機研究中得到證實。患者隨機給予apalutamide或安慰劑，並接受內分泌治療，包括接受促性腺激素釋放激素（GnRH）類似物，或者手術去勢（切除雙側睾丸）以降低體內雄激素水準。結果顯示，apalutamide治療組無轉移生存期相比安慰劑組顯著延長（40.5 vs 16.2個月）。

05 Trogarzo 2018年3月7日，美國FDA宣佈正式批准藥明生物合作夥伴中裕新藥(TaiMed)的Trogarzo上市，作為一種全新的抗逆轉錄病毒療法，治療現有多種療法均無法起效的成人HIV感染者。值得一提的是，這是美國FDA在2018年批准的首款創新生物藥，此專案也是藥明生物首個商業化生產的項目，標誌著藥明生物躋身成為全球少數幾個通過FDA GMP認證的生物藥合作研發生產服務商(CDMO)。Trogarzo是一種靜脈滴注的人源化免疫球蛋白G4單克隆抗體，它與CD4+ T細胞受體的第二個胞外區域結合，阻止HIV病毒入侵這些細胞。Trogarzo的安全性與療效在一項臨床試驗中得到了驗證。該試驗招募了40名感染有多重耐藥性HIV的患者，他們均重度經治，有些患者甚至已經接受過10種或更多的抗逆轉錄病毒療法。然而即便接受了大量治療，他們血液中的病毒水準(HIV-RNA)依舊很高。研究人員發現，在現有的療法中額外加入Trogarzo的治療後，只要短短一周，大部分患者血液中的HIV-RNA水準就有顯著下降。24周後，43%的患者其HIV-RNA水準依舊得到了抑制。對於這些急缺治療方案的患者，Trogarzo帶來了顯著益處。

06 Ilumya 3月20日，FDA批准ILUMYA 上市，用於適合接受全身治療或光療的中重度斑塊型銀屑病成人患者。據3期臨床試驗資料顯示，與安慰劑相比，施用ILUMYA 100 mg能取得顯著的臨床改善。研究通過兩次用藥後第12周至少75%的皮膚清除率（銀屑病面積敏感指數或PASI 75），以及醫師全面評估（PGA）評分"清除"或"最小"進行測量。其中，該研究有74%（229人）的患者在三次用藥後第28周達到75%的皮膚清除率，84%持續用藥的患者在第64周能維持PASI 75。毋庸置疑，ILUMYA是中度至重度斑塊型銀屑病臨床治療上的又一個重要突破。

07 Tavalisse  4月17日，美國FDA批准了Rigel製藥的TAVALISSE用於對之前治療緩解不佳的成年慢性免疫性血小板減少症（ITP）患者血小板減少的治療。TAVALISSE是一種口服的脾臟酪氨酸激酶(SYK)抑制劑，通過阻止血小板的破壞來應對疾病的潛在自身免疫原因，為成年慢性ITP患者提供了一個重要的新的治療方案。TAVALISSE的批准依賴於FIT臨床研究專案的資料，FIT包含兩項隨機安慰劑對照的臨床3期研究047和048、一項開標擴展試驗049以及最初的概念驗證試驗。新藥上市申請包括了163例ITP患者的資料，並得到了一項安全資料集的支持，該資料集包含4600多名涉及其它適應症的已接受TAVALISSE評估的受試者。

08 Crysvita 4月17日，美國FDA批准了Ultragenyx Pharmaceutical公司的新藥Crysvita，成為首個獲批治療1歲及以上兒童和成年人的X連鎖低磷血症（XLH）的藥物。XLH是一種罕見的遺傳性軟骨病，會造成血液中磷含量低，導致兒童和青少年的骨骼生長和發育受損，並使其一生都有骨礦化的問題。Crysvita獲批是基於4項臨床試驗中的安全性和療效資料。在一項安慰劑對照臨床試驗中，94％的每月接受一次Crysvita的成年人能達到正常的磷水準，而安慰劑組患者只有8％能達到這一水準。在兒童中，每兩周接受一次Crysvita的患者中有94％到100％能達到正常的磷水準。在兒童和成人中，接受Crysvita療法的患者的X光（與XLH相關）結果有所改善。把這些結果與自然歷史佇列相比較，也為Crysvita的有效性提供了支援。

09 Akynzeo  4月19日，FDA批准了瑞士製藥集團Helsinn公司的靜脈注射AKYNZEO，作為經歷CINV的患者的替代治療選擇。FDA已批准將AKYNZEO®IV與成人地塞米松聯合用於預防與高度致吐性癌症化療的初始和重複過程有關的急性和延遲性噁心和嘔吐。尚未研究AKYNZEO®用於預防與蒽環類加環磷醯胺化療相關的噁心和嘔吐 口服AKYNZEO在2014年被美國食品藥物管理局批准為固定組合口服藥，用於預防與癌症化療初期和重複過程有關的急性和延遲性噁心和嘔吐，包括但不限於高度致吐化療。AKYNZEO®靜脈注射製劑的批准為將這種重要治療選擇帶入更多患者採用新配方鋪平了道路，並將於2018年5月在美國推出此產品。

10 Lucemyra 5月16日，美國FDA宣佈批准US World Meds的Lucemyra（鹽酸洛非斯汀，lofexidine hydrochloride），用於緩解突然停用阿片類藥物的成人患者的戒斷症狀。雖然Lucemyra可以減輕戒斷症狀的嚴重程度，但它無法完全阻止這些症狀，並且最長只能使用14天。 Lucemyra的安全性和有效性得到了兩項隨機、雙盲、安慰劑對照臨床試驗的支援。這些臨床試驗共有866名符合阿片類藥物依賴診斷標準的成人患者，這些患者在生理上依賴于阿片類藥物，並正在進行阿片類藥物戒斷。這些研究使用Gossop短暫停藥量表（SOWS-Gossop）來評估療效，這是一種通過患者報告結果來評估阿片類戒斷症狀的工具。這些症狀包括感覺不適、胃痙攣、抽搐、感覺冷、心臟劇烈跳動、肌肉緊張、疼痛，打呵欠、流淚和失眠。

11 Aimovig5月17日，FDA批准了安進（Amgen）公司的Aimovig，作為成人偏頭痛的預防性治療，給藥方式為每月一次的自我注射，這也是FDA批准的首個預防性偏頭痛治療藥物。Aimovig獲批主要基於圍繞其展開的三項臨床試驗，試驗評估了其在偏頭痛預防中的安全性和有效性。 第一項研究包括955名有發作性偏頭痛病史的參與者，並將Aimovig與安慰劑進行比較。在6個月的時間裡，aimovig治療的患者平均每月的偏頭痛天數比服用安慰劑的患者少1到2個月。 第二項研究包括577名有發作性偏頭痛病史的患者，並將Aimovig與安慰劑進行比較。在三個月的時間裡，aimovig治療的患者平均每個月比服用安慰劑的病人少一次偏頭痛。 第三項研究對667例慢性偏頭痛患者進行了評估，並將Aimovig與安慰劑進行比較。在這項研究中，在三個月的時間裡，接受Aimovig治療的患者平均每月比接受安慰劑的患者少2次。臨床試驗中最常見的副作用是注射部位的反應和便秘。

12  Lokelma5月18日，美國FDA批准了阿斯利康（AstraZeneca）的新藥Lokelma用於治療罹患高鉀血症（hyperkalaemia）的成人患者。高血鉀風險在慢性腎病（CKD）患者以及服用普通心力衰竭（HF）藥物（如腎素-血管緊張素-醛固酮系統[RAAS]抑制劑）的患者中顯著增加，因為這種藥物會增加血鉀水準。Lokelma於今年3月底在歐盟獲批上市。次Lokelma獲得FDA的批准是基於三項雙盲、安慰劑對照試驗和兩項開放標籤試驗資料的支援。 這些研究表明，Lokelma的起效時間是服藥後1.0小時，達到正常血鉀水準的中位時間是2.2小時，92％的患者在基線後48小時內達到正常血鉀水準。該藥物的治療效果可維持長達12個月。

13  Doptelet 5月21日，美國FDA批准Dova Pharmaceuticals子公司AkaRx的新藥Doptelet片劑，用於治療計畫接受醫療或牙科手術的慢性肝病（CLD）成人患者的低血小板計數（血小板減少症）。Doptelet的安全性和有效性在兩項試驗（ADAPT-1和ADAPT-2）中得到了驗證。這些研究共包含435名慢性肝病和嚴重血小板減少症患者，他們將接受通常需要輸注血小板的手術。這些試驗評估了兩個劑量水準的口服Doptelet與安慰劑相比治療5天的效果。結果顯示，與安慰劑組相比，兩種劑量水準的Doptelet組有較高比例的患者具有增加的血小板計數，並且不需要在手術當天和治療後7天內接受血小板輸注或任何救援治療。Doptelet最常見的副作用有發燒、胃（腹）痛、噁心、頭痛、疲勞和手足腫脹（水腫）。

14  Doptelet  5月24日，FDA批准了BioMarin Pharmaceutical公司的Palynziq注射劑，用於降低苯丙酮尿症（PKU）成人患者的血液苯丙氨酸（Phe）水準，這些患者在現有管理下其血液Phe濃度無法控制在600微摩爾/升以內。Palynziq是一種聚乙二醇化的重組苯丙氨酸解氨酶，用來替代PKU患者缺乏的苯丙氨酸羥化酶（PAH）以分解Phe。在關鍵3期研究PRISM-2中，Palynziq與安慰劑相比顯著降低了血液Phe水準（p<0.0001），抵達了血液Phe變化的主要終點。在PRISM-2雙盲、安慰劑對照、隨機停藥期試驗（RWP）中，患者以2：1的比例被隨機分配繼續接受Palynziq治療（每日20 mg或每日40 mg）或接受安慰劑，持續8周。結果顯示，Palynziq組患者可以維持血液Phe濃度，而安慰劑組患者的血液Phe濃度恢復到治療前基線。

15  Olumiant 5月31日，美國FDA批准了禮來公司（Eli Lilly）新藥Olumiant上市，治療罹患中度至重度類風濕關節炎，卻無法從TNF抑制劑治療中受益的成人患者。由禮來與Incyte帶來的Olumiant就是這樣一款充滿潛力的新藥。它是一款每日一次的口服JAK抑制劑，能高效抑制JAK1、JAK2、以及TYK2。在人體內，不少細胞因數依賴於JAK的活性，其在不少炎性疾病和自身免疫疾病的發病過程中有潛在作用。通過抑制多種JAK的活性，Olumiant有望給類風濕關節炎患者帶來福音。

16  Epidioloex 6月25日，美國FDA批准了GW RESEARCH LTD新藥Epidiolex口服溶液治療兩歲及以上患者的兩種罕見和嚴重癲癇，Lennox-Gastaut綜合征和Dravet綜合征相關的癲癇發作。這是FDA批准的第一種含有從大麻中提取的純化藥物的藥物。這也是FDA首次批准用於治療Dravet綜合征患者的藥物。在三項隨機，雙盲，安慰劑對照的臨床試驗中研究了Epidiolex的有效性，該試驗涉及516名患有Lennox-Gastaut綜合征或Dravet綜合征的患者。與安慰劑相比，Epidiolex與其他藥物一起被證明可有效降低癲癇發作的頻率。

17  Zemdri 6月25日，美國FDA批准了Achaogen新藥Zemdri上市，用於由某些腸桿菌科細菌感染引起的、治療選擇非常有限或無治療選擇的複雜性尿路感染（cUTI，包括腎盂腎炎）成人患者，該藥是一種靜脈輸注藥物，每天給藥一次。 此次批准，使Zemdri成為治療cUTI的唯一一種每日一次的氨基糖苷類療法。plazomicin是一種新一代的氨基糖苷類抗生素，能夠抑制細菌蛋白質的翻譯過程。plazomicin是在西梭黴素（sisomicin）基礎上進行了化學改造而得，能避免被主要的氨基糖苷類抗生素鈍化酶（AME）破壞而失去活性。plazomicin開發用於治療MDR革蘭氏陰性菌腸桿菌科細菌導致的嚴重感染，包括對碳青黴烯類抗生素耐藥的腸桿菌。 Zemdri的獲批，是基於III期臨床研究EPIC的資料。該研究是首個評估每日一次氨基糖苷類療法治療cUTI（包括腎盂腎炎）的隨機對照研究，資料顯示，Zemdri達到了與美羅培蘭（meropenem）的非劣效性。

參考資料：1. Novel Drug Approvals for 20182. Novel Drug Approvals for 20173.2017年FDA批准的46個新藥匯總及國內進展簡述(https://news.yaozh.com/archive/21707.html)4.藥智資料中國臨床試驗資料庫5.新浪醫藥新聞(http://med.sina.com/)新聞來源：藥智網

Helsinn Group announces the launch of the IV formulation of AKYNZEO® (fosnetupitant/palonosetron) in the United States

8th May 2018  Lugano, Switzerland, and Iselin, NJ, United States, May 8, 2018 – Helsinn, a Swiss pharmaceutical group focused on building quality cancer care products, today announces that the intravenous formulation of AKYNZEO® (a fixed antiemetic combination of fosnetupitant, 235mg, and palonosetron, 0.25mg) for injection has been launched in the United States by its U.S. subsidiary, Helsinn Therapeutics (U.S.), Inc.. The FDA, on April 19, 2018, has approved AKYNZEO® IV in combination with dexamethasone in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy. AKYNZEO® for injection has not been studied for the prevention of nausea and vomiting associated with anthracycline plus cyclophosphamide chemotherapy.

Oral AKYNZEO® was previously approved by the FDA as a fixed combination oral agent in 2014 for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of cancer chemotherapy, including, but not limited to, highly emetogenic chemotherapy. AKYNZEO® is an oral fixed combination of palonosetron and netupitant: palonosetron prevents nausea and vomiting during the acute phase and netupitant prevents nausea and vomiting during both the acute and delayed phase after cancer chemotherapy. The bioequivalence of fosnetupitant and netupitant was demonstrated in a Phase 1 study and the safety of IV AKYNZEO® was established through a repeated dose safety study in cancer patients to potentially uncover adverse drug reactions that may appear during subsequent clinical practice. No anaphylactic and injection site reactions related to IV AKYNZEO® were reported in this study. A repeated dose safety study is ongoing in patients receiving anthracycline plus cyclophosphamide to further establish the safety profile in this setting. The prevention of CINV has significantly evolved over the past several decades. Currently the combination treatment of antiemetic medicines with different mechanisms of actions is recommended by the main international antiemetic guidelines for the prevention of CINV in most settings. Giorgio Calderari, Helsinn Group General Manager, commented: "Helsinn's mission is to help people with cancer get the most out of every day. We're delighted that we are now able to make this therapy available in intravenous formulation. This is an important moment for Helsinn, as it allows us to bring an additional option to patients experiencing CINV in highly emetogenic chemotherapy treatment." Paul Rittman, Chief Executive Officer of Helsinn Therapeutics, added: "We are delighted to launch the  further expand the presence of Helsinn in the U.S. in order to help even more people who are suffering from the emetogenic side effects of cancer treatment."

About Akynzeo®

AKYNZEO® (netupitant 300mg/palonosetron 0.5mg) capsules was approved October 2014 in the United States and is indicated in combination with dexamethasone in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of cancer chemotherapy, including, but not limited to, highly emetogenic chemotherapy.

AKYNZEO® (fosnetupitant 235mg/palonosetron 0.25) for injection was approved April 2018 in the United States and is indicated in combination with dexamethasone in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy.

Limitations of Use AKYNZEO for injection has not been studied for the prevention of nausea and vomiting associated with anthracycline plus cyclophosphamide chemotherapy. AKYNZEO is a combination of palonosetron, a serotonin-3 (5-HT3) receptor antagonist, and netupitant or fosnetupitant, substance P/neurokinin-1 (NK-1) receptor antagonists: palonosetron prevents nausea and vomiting during the acute phase and netupitant/fosnetupitant prevents nausea and vomiting during both the acute and delayed phase after cancer chemotherapy.