2024年1月8日，F(xiàn)DA的CDER發(fā)布了《2023年新藥治療審批報(bào)告》，從這個(gè)審批報(bào)告中我們可以了解到，2023年FDA批準(zhǔn)了55種創(chuàng)新藥物，這個(gè)數(shù)量遠(yuǎn)超于2022年的37種。另外，值得我們注意的是這55款獲批新藥中單孤兒藥就高達(dá)28個(gè)，占獲批藥物總數(shù)的51%（詳見(jiàn)圖1）。
圖1 CDER各年度新藥批準(zhǔn)數(shù)量
美國(guó)于1983年頒布了《孤兒藥法案》，成為世界上第一個(gè)為罕見(jiàn)病藥物立法的國(guó)家。之后為了鼓勵(lì)罕見(jiàn)病藥物的研發(fā)，美國(guó)通過(guò)了孤兒藥認(rèn)定（Orphan Drug Designation, ODD）計(jì)劃的一系列政策。孤兒藥認(rèn)定（Orphan Drug Designation, ODD）就是FDA 孤兒藥產(chǎn)品開(kāi)發(fā)辦公室（Office of Orphan Products Development， OOPD) 對(duì)符合條件的用于預(yù)防、治療及診斷罕見(jiàn)病的藥物（包括生物制品）授予的一種資格認(rèn)定。
近年來(lái)，國(guó)內(nèi)多家生物醫(yī)藥公司開(kāi)發(fā)的創(chuàng)新藥在美國(guó)獲得孤兒藥資格認(rèn)定，本文我們就盤(pán)點(diǎn)一下2023年中國(guó)制藥企業(yè)獲得FDA孤兒藥資格認(rèn)定的創(chuàng)新藥。
根據(jù)FDA的孤兒藥認(rèn)定數(shù)據(jù)庫(kù)資料初步統(tǒng)計(jì)，2023年獲得FDA授予的孤兒藥認(rèn)定的創(chuàng)新藥共有376種，其中中國(guó)的創(chuàng)新藥占59種（按適應(yīng)癥計(jì)）,約占15%（詳見(jiàn)表1）。
國(guó)內(nèi)制藥企業(yè)獲得FDA孤兒藥資格認(rèn)定的這些產(chǎn)品，從其適應(yīng)癥領(lǐng)域來(lái)看，多集中在腫瘤領(lǐng)域，占比高達(dá)63%（37/59），數(shù)量最多的5個(gè)癌種依次是胰腺癌（9項(xiàng)）、胃癌（5項(xiàng)）、惡性膠質(zhì)瘤（4項(xiàng)）、小細(xì)胞肺癌（3項(xiàng)）、膽道癌（2項(xiàng)）。除此之外，肌萎縮側(cè)索硬化癥和亨廷頓舞蹈癥關(guān)注度也較高。
另外，這些產(chǎn)品涵蓋了CAT-T療法、抗體偶聯(lián)藥物（ADC）、雙特異性抗體、基因療法等創(chuàng)新療法。
值得注意的是，有多家公司的多個(gè)產(chǎn)品同時(shí)被授予孤兒藥資格認(rèn)定。例如博安生物自主開(kāi)發(fā)的兩款靶向Claudin18.2的在研產(chǎn)品--創(chuàng)新抗體BA1105、創(chuàng)新抗體偶聯(lián)藥物BA1301獲得FDA授予的治療胰腺癌適應(yīng)癥的孤兒藥資格認(rèn)定;Suzhou Immunofoco Biotechnology Co., Ltd（易慕峰）是一家致力于突破實(shí)體瘤治療，給患者帶來(lái)長(zhǎng)期生存獲益的免疫細(xì)胞治療藥物開(kāi)發(fā)企業(yè)，其自主研發(fā)的靶向EpCAM的自體CAR-T細(xì)胞注射液產(chǎn)品獲得FDA授予的治療胃癌適應(yīng)癥的孤兒藥資格認(rèn)定，時(shí)隔不久該產(chǎn)品又被FDA授予孤兒藥資格認(rèn)定，用于治療胰腺癌患者;德琪（杭州）生物自主研發(fā)和開(kāi)發(fā)的Claudin 18.2抗體偶聯(lián)藥物（ADC）ATG-022獲FDA先后授予的兩項(xiàng)孤兒藥資格認(rèn)定，分別用于治療胃癌及胰腺癌。
表1 2023年獲得FDA授予孤兒藥資格認(rèn)定的中國(guó)藥企及產(chǎn)品
|
NO. |
藥品名稱(chēng) |
授予時(shí)間 |
適應(yīng)癥 |
MAH |
|
1 |
4-(3-(4-(1H-imidazo[4,5-b]pyridin-5-yl)piperazine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one hydrochloride dihydrate |
01/09/2023 |
小細(xì)胞肺癌(SCLC) |
Shanghai Yidian Pharmaceutical Technology Development Co., Ltd. 上海壹典醫(yī)藥科技開(kāi)發(fā)
|
|
2 |
recombinant adeno-associated virus serotype 8 vector encoding human phenylalanine hydroxylase (PAH) |
01/09/2023 |
苯丙酮尿癥（PKU） |
NGGT (Suzhou) Biotechnology Co., Ltd. |
|
3 |
N-(6-(2,6-dichloro-3,5-dimethoxyphenyl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-4-(3,3-dimethylpiperazin-1-yl)benzamide hydrochloride |
01/12/2023 |
胃癌和胃食管交界癌 |
3D Medicines (Beijing) Co., Ltd |
|
4 |
(S)-N-(5-(1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl)-4,6-dioxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)acetamide |
01/18/2023 |
白塞病 |
Ganzhou Hemay Pharmaceutical Co., Ltd.合美醫(yī)藥 |
|
5 |
5¿-(4-fluorophenyl)-3¿-isopropyl-N-(4-(4-methylpiperazin-1-yl) phenyl)-1H,3¿H-[2,4¿-biimidazole]-4-carboxamide acetate |
02/01/2023 |
特發(fā)性肺纖維化 |
InSilico Medicine Hong Kong Limited英矽智能 |
|
6 |
(-)-B-Elemene（ KH617） |
02/14/2023 |
多型膠質(zhì)母細(xì)胞瘤 |
Sichuan Honghe Biotechnology Co., Ltd.四川弘合生物科技 |
|
7 |
a humanized, immunoglobulin G subtype 4 anti-Amphiregulin monoclonal antibody |
02/16/2023 |
特發(fā)性肺纖維化 |
Pulmongene (Hong Kong) Co., Limited普沐(香港)生物科技有限公司 |
|
8 |
allogeneic T cells genetically modified to express anti-B7-H3 chimeric antigen receptor (CAR) |
02/16/2023 |
惡性膠質(zhì)瘤 |
T-MAXIMUM Pharmaceutical (Suzhou) Co., Ltd. |
|
9 |
Mefuparib |
02/28/2023 |
膽道癌 |
Convalife (Shanghai) Co., Ltd.甫康（上海）健康科技 |
|
10 |
siRNA oligonucleotide designed to target and knockdown the expression of SOD1 |
03/01/2023 |
肌萎縮側(cè)索硬化癥（ALS） |
Ractigen Therapeutics中美瑞康 |
|
11 |
Autologous CD4+/CD8+ T cells transduced with lentiviral vector directed against MAGE-A4 antigen |
03/23/2023 |
IIB至IV期黑色素瘤 |
TCRx Therapeutics Ltd.科士華生物 |
|
12 |
Humanized, Low-fucose Anti-Claudin 18.2 IgG1 Antibody |
03/23/2023 |
胰腺癌 |
Suzhou Transcenta Therapeutics Co., Ltd.創(chuàng)勝集團(tuán) |
|
13 |
3-(5-cyano-4-(cyclopropylamino)pyridin-2-yl)-1-(6-formyl-5-((4-methyl-2-oxopiperazin-1-yl)methyl)pyridin-2-yl)-1-methylurea |
03/27/2023 |
軟組織肉瘤 |
Wuxi Abbisko Biomedical Technology Co., Ltd.和譽(yù)生物醫(yī)藥 |
|
14 |
a multiple substituted pyrimidoheterocycle small molecule inhibitor that covalently binds to the Switch II pocket of KRAS p.G12C and locks the oncogenic protein in its GDP-bound inactive form |
03/27/2023 |
攜帶KRAS p.G12C突變蛋白的晚期癌癥 |
D3 Bio (Wuxi) Co., Ltd.德昇濟(jì) |
|
15 |
A plasmid encoding a rabies virus glycoprotein tag & lysosome-associated membrane glycoprotein 2 fusion protein gene and a mutant huntingtin small interfering RNA |
04/10/2023 |
亨廷頓舞蹈癥 |
ExoRNA Bioscience Nanjing Co. Ltd. |
|
16 |
(2-(6-(2-(4-cyclopropylpyrimidin-5-yl)-4-fluorophenoxy)-1,2,4-triazin-5-yl)-2,7-diazaspiro[3.5]nonan-7-yl)((1S,3aR,6aS)-octahydrocyclopenta[c]pyrrol-1-yl)methanone |
04/17/2023 |
急性髓細(xì)胞白血病 |
BioNova Pharmaceuticals (Shanghai) Limited燁輝醫(yī)藥 |
|
17 |
Edralbrutinib |
04/24/2023 |
視神經(jīng)脊髓炎譜系障礙 |
Reistone Biopharma Company Limited瑞石生物醫(yī)藥 |
|
18 |
allogeneic umbilical cord mesenchymal stem cells |
05/03/2023 |
眼部移植物抗宿主病 |
Guangdong ProCapZoom Biosciences Co., Ltd.廣東普羅凱融生物醫(yī)藥 |
|
19 |
Autologous Chimeric Antigen Receptor (CAR) Modified Recombinant T Cells Targeting EGFRvIII |
05/09/2023 |
惡性膠質(zhì)瘤 |
Beijing DCTY® Biotech Co., Ltd.北京鼎成肽源生物技術(shù) |
|
20 |
N-[3-fluoro-4-[[1-methyl-6-(1H-pyrazol-4-yl)-1H-indazol-5-yl]oxy]phenyl]-1-(4-fluorophenyl)-1,2-dihydro-6-(1-methylethoxy)-2-oxo-3-pyridinecarboxamide(多靶點(diǎn)激酶抑制劑TSN084) |
05/16/2023 |
用于治療急性髓系白血病 |
Tyligand Bioscience (Shanghai) Limited泰勵(lì)生物 |
|
21 |
Antibody drug conjugate targeting Claudin 18.2 (CLDN 18.2) consisting of a humanized monoclonal antibody against CLDN 18.2 and a conjugated linker-payload VC-MMAE (maleimidocaproyl-valine-citrulline-p-aminobenzylalcohol-Monomethyl Auristatin E) |
05/16/2023 |
胰腺癌 |
Antengene (Hangzhou) Biologics Co., Ltd.德琪(杭州)生物 |
|
22 |
autologous CD3+ T cell product transduced with transgene constructs expressing anti-human mesothelin (MSLN) CAR and self-secreting anti-human PD-1 nanobody |
05/16/2023 |
間皮瘤 |
Shanghai Cell Therapy Group Pharmaceutical Technology Co., Ltd上海細(xì)胞治療集團(tuán) |
|
23 |
antibody drug conjugate targeting Claudin 18.2 (CLDN 18.2) consisting of a humanized monoclonal antibody against CLDN 18.2 and a conjugated linker-payload VC-MMAE (maleimidocaproyl-valine-citrulline-p-aminobenzylalcohol-Monomethyl Auristatin E) |
05/22/2023 |
胃癌 |
Antengene (Hangzhou) Biologics Co., Ltd德琪(杭州)生物 |
|
24 |
Recombinant humanized anti-MSLN monoclonal antibody- monomethyl auristatin E conjugate |
05/22/2023 |
胰腺癌 |
RemeGen Co., Ltd榮昌生物 |
|
25 |
chimeric antigen receptor (CAR) modified recombinant T cells targeting B7-H3 |
06/21/2023 |
惡性膠質(zhì)瘤 |
Fuzhou Tcelltech Biological Science and Technology Inc. |
|
26 |
Pegylated Iron Oxide Nanoparticles |
06/26/2023 |
肝細(xì)胞癌的治療的診斷 |
MegaPro Biomedical Company, Ltd.巨生生醫(yī) |
|
27 |
human umbilical cord-derived mesenchymal stem cells |
08/09/2023 |
特發(fā)性肺纖維化 |
Wuhan Optics Valley Vcanbiopharma Co., Ltd. |
|
28 |
Autologous synthetic NKG2D receptor armored CLDN18.2 specific CAR-T cell injection |
08/15/2023 |
胃癌 |
Suzhou Immunofoco Biotechnology Co., Ltd易慕峰 |
|
29 |
Autologous EpCAM specific CAR-T cell injection |
08/16/2023 |
胃癌 |
Suzhou Immunofoco Biotechnology Co., Ltd易慕峰 |
|
30 |
a genetically modified Salmonella comprising of methioninase |
08/28/2023 |
小細(xì)胞肺癌 |
Guangzhou Sinogen Pharmaceutical Co., Ltd.廣州華津醫(yī)藥 |
|
31 |
Autologous synthetic NKG2D receptor armored CLDN18.2 specific CAR-T cell injection |
08/28/2023 |
胰腺癌 |
Suzhou Immunofoco Biotechnology Co., Ltd易慕峰 |
|
32 |
autologous chimeric antigen receptor (CAR) T cells targeting CD7 |
08/31/2023 |
急性淋巴細(xì)胞白血病和淋巴細(xì)胞淋巴瘤 |
Hebei Senlang Biotechnology Co. Ltd.河北森朗生物 |
|
33 |
N( 4{[ 5fluoro7( 2methoxyethoxy) 4quinazolinyl] amino}phenyl)2( 4isopropyl1H1,2,3triazol1yl) acetamide 4-methylbenzenesulfonate (1:1) |
09/13/2023 |
胃腸道間質(zhì)瘤（GIST） |
Ningbo NewBay Technology Development Co., Ltd.寧波新灣醫(yī)藥 |
|
34 |
(R)-3-(5,5-dimethyl-4,5-dihydro-1,2,4-oxadiazol-3-yl)-N-(1-(2,3,5-trifluorophenyl) ethyl) pyrazolo[1,5-a] pyrimidin-5-amine hydrate |
09/19/2023 |
ALK陽(yáng)性、ROS1陽(yáng)性、NTRK融合陽(yáng)性或LTK陽(yáng)性非小細(xì)胞肺癌 |
TYK Medicines, Inc 同源康 |
|
35 |
Folate-TRPV6-peptide exatecan drug conjugate （CBP-1019） |
09/19/2023 |
胰腺癌 |
Coherent Biophanna (Hefei) Co., Ltd.同宜醫(yī)藥 |
|
36 |
Human Retinal Pigment Epithelial Cell Injection |
09/19/2023 |
色素性視網(wǎng)膜炎 |
Eyecure Therapeutics Inc.江蘇艾爾康生物醫(yī)藥科技 |
|
37 |
A Lipid Nanoparticle Suspension of Akt-1 Antisense Oligonucleotide |
09/20/2023 |
肝細(xì)胞癌 |
Zhejiang Haichang Biotech Co., Ltd.浙江海昶生物醫(yī)藥技術(shù)有限公司 |
|
38 |
((2S,5S)-5-(4-amino-5-(4-(2,3-difluorophenoxy)phenyl)imidazo[5,1-f][1,2,4]triazin-7-yl)tetrahydro-2H-pyran-2-yl)methanol |
10/02/2023 |
用于治療中樞神經(jīng)系統(tǒng)淋巴瘤 |
Dizal (Jiangsu) Pharmaceutical Co., Ltd.迪哲(江蘇)醫(yī)藥 |
|
39 |
recombinant adeno-associated virus vector serotype 8 carrying the coding sequence of human GBA1 gene |
10/05/2023 |
戈謝病 |
Lingyi Biotech Co. Ltd凌意（杭州）生物科技 |
|
40 |
Virus-like particle containing Cas9/gRNA ribonucleoprotein targeting the human HTT gene |
10/05/2023 |
亨廷頓舞蹈癥 |
Shanghai BDgene Co., Ltd.上海本島基因 |
|
41 |
adeno-associated virus (AAV) vector-based gene therapy delivering a therapeutic transgene of RJK002 |
10/16/2023 |
肌萎縮側(cè)索硬化癥 |
Rejukon Biopharm Inc.瑞吉康生物醫(yī)藥有限公司 |
|
42 |
recombinant humanized anti-interleukin 36R monoclonal antibody |
10/16/2023 |
泛發(fā)性膿皰型銀屑病 |
Shanghai Huaota Biopharmaceutical Co., Ltd.上海華奧泰生物藥業(yè) |
|
43 |
N-(2-(4-Fluorophenyl)-5,7-dimethyl-1,2,3,4-tetrahydro isoquinolin-6-yl)-2-(1-methylcyclopropyl) acetamide |
10/18/2023 |
肌萎縮側(cè)索硬化癥 |
Shanghai Zhimeng Biopharma, Inc上海摯盟醫(yī)藥科技 |
|
44 |
Recombinant human signal regulating protein alpha (SIRPalpha) fragment crystallizable (Fc)-fusion protein |
11/07/2023 |
慢性粒單核細(xì)胞白血?。–MML） |
ImmuneOnco Biopharmaceuticals (Shanghai) Inc.宜明昂科 |
|
45 |
Recombinant human IgG1 anti-B7H3 monoclonal antibody conjugated to topoisomerase I inhibitor YL0010014 |
11/16/2023 |
食管癌 |
MediLink Therapeutics蘇州宜聯(lián)生物醫(yī)藥 |
|
46 |
Allogenic spinal motor neuron precursor cell |
11/22/2023 |
肌萎縮側(cè)索硬化癥（ALS） |
XellSmart Bio-Pharmaceutical (Suzhou) Co., Ltd士澤生物醫(yī)藥(蘇州) |
|
47 |
Epirubicin |
11/28/2023 |
惡性膠質(zhì)瘤 |
Beijing Inno Medicine Co., Ltd.茵諾醫(yī)藥 |
|
48 |
Chaenomelis Fructus Extract |
11/29/2023 |
BAG3相關(guān)肌原纖維肌病 |
Centre for Chinese Herbal Medicine Drug Development Limited中藥創(chuàng)新研發(fā)中心 |
|
49 |
a bispecific antibody composed of a Light Chain and a Heavy Chain pair targeting HER2, and a Light Chain and a Heavy Chain pair targeting CD47 |
12/07/2023 |
胃癌癥患者的治療，包括胃食管交界處癌癥 |
D3 Bio (Wuxi) Co., Ltd.德昇濟(jì) |
|
50 |
Tetrahydro-2H-pyran-4-yl 7-(2-(cyclopropanecarboxamido)- imidazo[1,2-a]pyridin-6-yl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine-1-carboxylate hydrochloride |
12/11/2023 |
急性移植物抗宿主病 |
Accro Bioscience (Suzhou) Limited愛(ài)科諾生物醫(yī)藥(蘇州)有限公司 |
|
51 |
(-)-Huperzine A石杉?jí)A甲 |
12/12/2023 |
重癥肌無(wú)力 |
Wanbangde Pharmaceutical Group Co, Ltd.萬(wàn)邦德制藥 |
|
52 |
recombinant humanized anti-human tissue factor monoclonal antibody conjugated with a cytotoxic small molecule MMAE |
12/12/2023 |
胰腺癌 |
Shanghai Miracogen Inc.上海美雅珂生物 |
|
53 |
trastuzumab-rezetecan |
12/14/2023 |
膽道癌 |
Jiangsu Hengrui Pharmaceuticals Co., Ltd. 恒瑞醫(yī)藥 |
|
54 |
recombinant fusion protein composed of a recombinant human arylsulfatase A (rhARSA) fused with a variable domain of the heavy chain of heavy chain-only antibody fragment targeting human transferrin |
12/15/2023 |
異染性腦白質(zhì)營(yíng)養(yǎng)不良 |
Linno Pharmaceuticals, Inc.領(lǐng)諾醫(yī)藥 |
|
55 |
an IgG1(Immunoglobulin G1) subclass antibody targeting CCR8(C-C Motif Chemokine Receptor 8) |
12/18/2023 |
胰腺癌 |
LaNova Medicines Limited禮新醫(yī)藥 |
|
56 |
Adeno-associated viruses 8 (AAV8)-based gene therapy vector that expresses B domain-deleted human factor VIII under the control of human liver-specific promoters |
12/19/2023 |
血友病A |
Gritgen Therapeutics Co., Ltd.華毅樂(lè)健 |
|
57 |
anti-Claudin18.2 monoclonal antibody conjugated with Duostatin-5 payload |
12/21/2023 |
胰腺癌 |
Shandong Boan Biotechnology Co., Ltd.博安生物 |
|
58 |
Human monoclonal IgG1 antibody against the isoform 2 of human Claudin 18 protein (Claudin 18.2) |
12/21/2023 |
胰腺癌 |
Shandong Boan Biotechnology Co., Ltd.博安生物 |
|
59 |
Dual recombinant adeno-associated viral vectors encoding the human otoferlin gene |
12/21/2023 |
耳啡肽介導(dǎo)的聽(tīng)力損失 |
Shanghai Refreshgene Therapeutics Co., Ltd.上海鼎新基因科技 |
分析
從上面這些數(shù)據(jù)看，國(guó)內(nèi)創(chuàng)新藥企業(yè)對(duì)美國(guó)孤兒藥的政策很熟悉，并且充分運(yùn)用。對(duì)于研發(fā)成本高啟的美國(guó)醫(yī)藥市場(chǎng)，可以通過(guò)孤兒藥資格認(rèn)定這條途徑，開(kāi)啟合適的臨床試驗(yàn)并控制研發(fā)費(fèi)用，對(duì)于創(chuàng)新藥公司是一條不錯(cuò)的開(kāi)辟途徑。
參考資料：
1-FDA官網(wǎng)
2-FDA《2023年新藥治療審批報(bào)告》
作者簡(jiǎn)介：zhulikou431，高級(jí)工程師、PDA會(huì)員、ISPE會(huì)員、ECA會(huì)員、PQRI會(huì)員、資深無(wú)菌GMP專(zhuān)家，在無(wú)菌工藝開(kāi)發(fā)和驗(yàn)證、藥品研發(fā)和注冊(cè)、CTD文件撰寫(xiě)和審核、法規(guī)審計(jì)、國(guó)際認(rèn)證、國(guó)際注冊(cè)、質(zhì)量體系建設(shè)與維護(hù)領(lǐng)域，以及無(wú)菌檢驗(yàn)、環(huán)境監(jiān)控等領(lǐng)域皆具有較深造詣。近幾年開(kāi)始著力關(guān)注制藥宏觀領(lǐng)域趨勢(shì)分析和制藥企業(yè)并購(gòu)項(xiàng)目的風(fēng)險(xiǎn)管理工作。
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