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Category Archives: Monoclonal antibody
DRUG APPROVALS BY DR ANTHONY MELVIN CRASTO
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Bococizumab
Bococizumab
PF-04950615, RN-316, RN316
PCSK9 (proprotein convertase subtilisin/kexin type 9, neural apoptosis-regulated convertase 1, NARC1, NARC-1, proproteine convertase 9, PC9) [Homo sapiens]
IgG2 – kappa
Hypercholesterolemia
Cardiovascular diseases
STRUCTURAL FORMULA
Heavy chain
QVQLVQSGAE VKKPGASVKV SCKASGYTFT SYYMHWVRQA PGQGLEWMGE 50
ISPFGGRTNY NEKFKSRVTM TRDTSTSTVY MELSSLRSED TAVYYCARER 100
PLYASDLWGQ GTTVTVSSAS TKGPSVFPLA PCSRSTSEST AALGCLVKDY 150
FPEPVTVSWN SGALTSGVHT FPAVLQSSGL YSLSSVVTVP SSNFGTQTYT 200
CNVDHKPSNT KVDKTVERKC CVECPPCPAP PVAGPSVFLF PPKPKDTLMI 250
SRTPEVTCVV VDVSHEDPEV QFNWYVDGVE VHNAKTKPRE EQFNSTFRVV 300
SVLTVVHQDW LNGKEYKCKV SNKGLPSSIE KTISKTKGQP REPQVYTLPP 350
SREEMTKNQV SLTCLVKGFY PSDIAVEWES NGQPENNYKT TPPMLDSDGS 400
FFLYSKLTVD KSRWQQGNVF SCSVMHEALH NHYTQKSLSL SPGK 444
Light chain
DIQMTQSPSS LSASVGDRVT ITCRASQGIS SALAWYQQKP GKAPKLLIYS 50′
ASYRYTGVPS RFSGSGSGTD FTFTISSLQP EDIATYYCQQ RYSLWRTFGQ 100′
GTKLEIKRTV AAPSVFIFPP SDEQLKSGTA SVVCLLNNFY PREAKVQWKV 150′
DNALQSGNSQ ESVTEQDSKD STYSLSSTLT LSKADYEKHK VYACEVTHQG 200′
LSSPVTKSFN RGEC 214′
Disulfide bridges location
22-96 22”-96” 23′-88′ 23”’-88”’ 132-214′ 132”-214”’
134′-194′ 134”’-194”’ 145-201 145”-201” 220-220” 221-221”
224-224” 227-227” 258-318 258”-318” 364-422 364”-422”
Bococizumab nonproprietary drug name
RN-316, PF-04950615
target-PC9
USAN (AB-55) BOCOCIZUMAB
PRONUNCIATION boe” koe siz’ ue mab
THERAPEUTIC CLAIM Treatment of dyslipidemia
CHEMICAL NAME
1. Immunoglobulin G2, anti-(human neural apoptosis-regulated proteinase
1)(human-Mus musculus monoclonal PF-04950615 heavy chain), disulfide
with human-Mus musculus monoclonal PF-04950615 light chain, dimer
2. Immunoglobulin G2-kappa, anti-[human proprotein convertase subtilisin/hexin type 9 (neural apoptosis-regulated convertase 1, PC9)], humanized mouse monoclonal antibody; gamma 2 heavy chain (1-444) [humanized VH (Homo sapiens IGHV1-46-1*03 (90.8%) -(IGHD)-IGHJ6*01) [8.8.11] (1-118)-Homo sapiens IGHG2*01 CH2A100>S(327),CH2P101>S(328) (119-444)] (132-214′)-
disulfide with kappa light chain (1′-214′) [humanized V-KAPPA (Homo sapiensIGKV1-39*01 (88.2%)-IGKJ2*01 [6.3.9] (1′-107′)-IGKC*01 (108′-214′)]; dimer
(220-220”:221-221”:224-224”:227-227”)-tetrakisdisulfide
MOLECULAR FORMULA C6414H9918N1722O2012S54
MOLECULAR WEIGHT 145.1 kDa
TRADEMARK None as yet
SPONSOR Pfizer, Inc.
CODE DESIGNATIONS RN316, PF-04950615
CAS REGISTRY NUMBER 1407495-02-6
WHO NUMBER 9840
Bococizumab[1] (RN316)[2] is a drug in development by Pfizer targeting PCSK9 to reduce LDL cholesterol.[3]
Description
Bococizumab is a monoclonal antibody that inhibits PCSK9, a protein that interferes with the removal of LDL. LDL levels are a major risk factor for cardiovascular disease.
Clinical trials
A phase 2b study of statin patients was presented at the 2014 American College of Cardiology. Monthly or bimonthly injections resulted in significantly reduced LDL-C at week 12.
The Phase 3 SPIRE trials plan to enroll 17,000 patients to measure cardiovascular risk. High risk and statin intolerant subjects will be included.
References
- “Statement On A Nonproprietary Name Adopted By The USAN Council: Bococizumab” (PDF). American Medical Association.
- World Health Organization (2013). “International Nonproprietary Names for Pharmaceutical Substances (INN). Proposed INN: List 110”(PDF). WHO Drug Information 27 (4).
- “Bococizumab (RN316) Significantly Reduced LDL Cholesterol In Statin-Treated Adults With High Cholesterol In A Phase 2b Study”. Retrieved 29 December 2014.
| Monoclonal antibody | |
|---|---|
| Type | Whole antibody |
| Source | Humanized (from mouse) |
| Target | Proprotein convertase subtilisin/kexin type 9 (PCSK9) |
| Clinical data | |
| Legal status |
|
| Routes of administration |
Subcutaneous injection |
| Identifiers | |
| CAS Registry Number | 1407495-02-6 |
| ATC code | None |
| PubChem | SID: 194168554 |
| IUPHAR/BPS | 7730 |
| ChEMBL | CHEMBL3137349 |
| Chemical data | |
| Formula | C6414H9918N1722O2012S54 |
| Molecular mass | 145.1 kDa |
//////
Japanese filing for Amgen’s PCSK9 inhibitor Repatha
Amgen has filed its closely watched PCSK9 inhibitor Repatha (evolocumab) in Japan for the treatment of high cholesterol.
Repatha is an investigational fully human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9), a protein that reduces the liver’s ability to remove low-density lipoprotein cholesterol (LDL-C), or ‘bad’ cholesterol, from the blood.
| Monoclonal antibody | |
|---|---|
| Type | Whole antibody |
| Source | Human |
| Target | PCSK9 |
| Clinical data | |
|
|
| Subcutaneous injection | |
| Identifiers | |
| 1256937-27-5 | |
| C10AX13 | |
| Chemical data | |
| Formula | C6242H9648N1668O1996S56 |
| 141.8 kDa | |
Evolocumab[1] (also known as compound number AMG-145 or AMG145)[2] is a monoclonal antibody designed for the treatment of hyperlipidemia.[3] Evolocumab is a fully human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9).
PCSK9 is a protein that targets LDL receptors for degradation and thereby reduces the liver’s ability to remove LDL-C, or “bad” cholesterol, from the blood.
Evolocumab, being developed by Amgen scientists, is designed to bind to PCSK9 and inhibit PCSK9 from binding to LDL receptors on the liver surface. In the absence of PCSK9, there are more LDL receptors on the surface of the liver to remove LDL-C from the blood.
Clinical trials
Two trials have been in progress as at mid-2014:
On 23 January 2014 Amgen announced that the Phase 3 GAUSS-2 (Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects-2) trial evaluating evolocumab in patients with high cholesterol who cannot tolerate statins met its co-primary endpoints: the percent reduction from baseline in low-density lipoprotein cholesterol (LDL-C) at week 12 and the mean percent reduction from baseline in LDL-C at weeks 10 and 12. The mean percent reductions in LDL-C, or “bad” cholesterol, compared to ezetimibe were consistent with results observed in the Phase 2 GAUSS study.[4][5]
The GAUSS-2 trial evaluated safety, tolerability and efficacy of evolocumab in 307 patients with high cholesterol who could not tolerate effective doses of at least two different statins due to muscle-related side effects. Patients were randomly assigned to one of four treatment groups: subcutaneous evolocumab 140 mg every two weeks and oral placebo daily; subcutaneous evolocumab 420 mg monthly and oral placebo daily; subcutaneous placebo every two weeks and oral ezetimibe 10 mg daily; or subcutaneous placebo monthly and oral ezetimibe 10 mg daily.
Safety was generally balanced across treatment groups. The most common adverse events (> 5 percent in evolocumab combined group) were headache (7.8 percent evolocumab; 8.8 percent ezetimibe), myalgia (7.8 percent evolocumab; 17.6 percent ezetimibe), pain in extremity (6.8 percent evolocumab; 1.0 percent ezetimibe), and muscle spasms (6.3 percent evolocumab; 3.9 percent ezetimibe).
Cholesterol-lowering treatment with a statin as part of follow-up care can help reduce a patient’s risk after myocardial infarction, ischaemic stroke or TIA.
The FOURIER Phase 3 clinical study http://www.fourierstudy.com/ seeks to find out whether lowering cholesterol by an additional 50% might reduce this risk even further. Several sites in the UK are part of this very large clinical study, lasting up to five years, and it is hoped that the study will help guide future clinical practice.
Evolocumab (also formerly known as AMG145, from Amgen) binds to PCSK9, a natural protein produced by the liver. By binding to PCSK9, evolocumab allows the LDL receptor (a protein present in the liver) to move LDL-cholesterol out of the bloodstream more efficiently. This study is designed to see whether treatment of dyslipidemia with evolocumab in people who have experienced a prior myocardial infarction, ischaemic stroke or TIA, and who are taking a highly effective dose of a statin, reduces the risk of recurring or additional cardiovascular events. Participants in this study have clinically evident cardiovascular disease.
READ AT
MY EARLIER ARTICLE
References
- World Health Organization (2012). “International Nonproprietary Names for Pharmaceutical Substances (INN). Proposed INN: List 108” (PDF). WHO Drug Information 26 (4).
- 2
- Sheridan, C (2013). “Phase 3 data for PCSK9 inhibitor wows”. Nature Biotechnology 31 (12): 1057–8. doi:10.1038/nbt1213-1057. PMID 24316621.
- 3
- Statement On A Nonproprietary Name Adopted By The USAN Council – Evolocumab
- 4
- Estel Grace Masangkay, “Amgen Phase III GAUSS-2 Trial of Evolocumab (AMG 145) Meets Co-Primary Endpoints Of LDL Cholesterol Reduction”, Bioresearch Online (January 24 2014)
- 5
Pierson, Ransdell (17 March 2014). “Amgen drug meets goal for those with high genetic cholesterol”. Associated Press. Retrieved 19 March 2014.
FDA expands approved use of Opdivo to treat lung cancer
March 4, 2015
Release
The U.S. Food and Drug Administration today expanded the approved use of Opdivo (nivolumab) to treat patients with advanced (metastatic) squamous non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy.
Lung cancer is the leading cause of cancer death in the United States, with an estimated 224,210 new diagnoses and 159,260 deaths in 2014. The most common type of lung cancer, NSCLC affects seven out of eight lung cancer patients, occurring when cancer forms in the cells of the lung.
Opdivo works by inhibiting the cellular pathway known as PD-1 protein on cells that blocks the body’s immune system from attacking cancerous cells. Opdivo is intended for patients who have previously been treated with platinum-based chemotherapy.
“The FDA worked proactively with the company to facilitate the early submission and review of this important clinical trial when results first became available in late December 2014,” said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “This approval will provide patients and health care providers knowledge of the survival advantage associated with Opdivo and will help guide patient care and future lung cancer trials.”
Opdivo’s efficacy to treat squamous NSCLC was established in a randomized trial of 272 participants, of whom 135 received Opdivo and 137 received docetaxel. The trial was designed to measure the amount of time participants lived after starting treatment (overall survival). On average, participants who received Opdivo lived 3.2 months longer than those participants who received docetaxel.
The safety and efficacy of Opdivo to treat squamous NSCLC was supported by a single-arm trial of 117 participants who had progressed after receiving a platinum-based therapy and at least one additional systemic regimen. The study was designed to measure objective response rate (ORR), or the percentage of participants who experienced partial shrinkage or complete disappearance of the tumor. Results showed 15 percent of participants experienced ORR, of whom 59 percent had response durations of six months or longer.
The most common side effects of Opdivo are fatigue, shortness of breath, musculoskeletal pain, decreased appetite, cough, nausea and constipation. The most serious side effects are severe immune-mediated side effects involving healthy organs, including the lung, colon, liver, kidneys and hormone-producing glands.
Opdivo for squamous NSCLC was reviewed under the FDA’s priority review program, which provides for an expedited review of drugs that treat serious conditions and, if approved, would provide significant improvement in safety or effectiveness in the treatment of a serious condition. Opdivo is being approved more than three months ahead of the prescription drug user fee goal date of June 22, 2015, the date when the agency was scheduled to complete its review of the application.
The FDA previously approved Opdivo to treat patients with unresectable (cannot be removed by surgery) or metastatic melanoma who no longer respond to other drugs.
Opdivo is marketed by Princeton, New Jersey-based Bristol-Myers Squibb.
Shirdi – Wikipedia, the free encyclopedia
pronunciation (help·info) (Marathi: शिर्डी) is a town and falls under the jurisdiction of municipal council popularly known as Shirdi Nagar Panchayat, located …
.
Shraddha Inn,Shirdi
SHIRDI PRASADALAYA BOJAN
Solar Kitchen Feeds Many at Shirdi, India Shrine
Rajdhani Restaurant: Rajdhani at Shirdi
The well equipped kitchen provides food two times a day, daily. Around 27, 000 of people are distributed food at cheap rate. The food comprises of dal,
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Novartis obtains European approval for Cosentyx to treat psoriasis
Novartis obtains European approval for Cosentyx to treat psoriasis
Swiss drug-maker Novartis has received approval from the European Commission (EC) for its Cosentyx (secukinumab, formerly known as AIN457) to treat moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy.SEE
PSORIAIS
secukinumab
Secukinumab is a human monoclonal antibody designed for the treatments of uveitis, rheumatoid arthritis, ankylosing spondylitis, and psoriasis. It targets member A from the cytokine family of interleukin 17.[1][2] At present, Novartis Pharma AG, the drug’s developer, plans to market it under the trade name “Cosentyx.” [3] It is highly specific to the human immunoglobulin G1k (IgG1k) subclass.[2]
In July 2014 secukinumab established superiority to placebo and to etanercept for the treatment of chronic plaque psoriasis in Phase III clinical trials.[4] In October 2014, the FDA Dermatologic and Ophthalmic Drugs Advisory Committee unanimously voted to recommend the drug for FDA approval, although this vote in and of itself does not constitute an approval. However, the FDA typically follows recommendations from these committees.[5] In October 2014, Novartis announced that the drug had achieved a primary clinical endpoint in two phase III clinical trials for ankylosing spondylitis.[6] As of 28 October, the relevant FDA committee had not yet responded to these results. In early November 2014, Novartis also released the results of a Phase 3 study on Psoriatic Arthritis that yielded very promising results.[7]
Although the drug was originally intended to treat rheumatoid arthritis, phase II clinical trials for this condition yielded disappointing results.[8] Similarly, while patients in a phase II clinical trial for [psoriatic arthritis] did show improvement over placebo, the improvement did not meet adequate endpoints and Novartis is considering whether to do more research for this condition.[9] Novartis has said that it is targeting approval and release in early 2015 for plaque psoriasis and ankyloding spondylitis indications.
It is also in a phase II clinical trial for Multiple Sclerosis [10] as it has exhibited efficacy in treating experimental autoimmune encephalomyelitis (EAE), an animal model of MS.
CAS registry numbers
- 875356-43-7 (heavy chain)
- 875356-44-8 (light chain)
References
- “Statement On A Nonproprietary Name Adopted By The USAN Council: Secukinumab”. American Medical Association.
- Hueber, W.; Patel, D. D.; Dryja, T.; Wright, A. M.; Koroleva, I.; Bruin, G.; Antoni, C.; Draelos, Z.; Gold, M. H.; Psoriasis Study, P.; Durez, P. P.; Tak, J. J.; Gomez-Reino, C. S.; Rheumatoid Arthritis Study, R. Y.; Foster, C. M.; Kim, N. S.; Samson, D. S.; Falk, D.; Chu, Q. D.; Callanan, K.; Nguyen, A.; Uveitis Study, F.; Rose, K.; Haider, A.; Di Padova, F. (2010). “Effects of AIN457, a Fully Human Antibody to Interleukin-17A, on Psoriasis, Rheumatoid Arthritis, and Uveitis”. Science Translational Medicine 2 (52): 52ra72.doi:10.1126/scitranslmed.3001107. PMID 20926833.
- http://www.medscape.com/viewarticle/835331
- Langley RG, Elewski BE, Mark Lebwohl M, et al., for the ERASURE and FIXTURE Study Groups (July 24, 2014). “Secukinumab in Plaque Psoriasis — Results of Two Phase 3 Trials”. N Engl J Med 371: 326–338. doi:10.1056/NEJMoa1314258.
- committees.http://www.familypracticenews.com/index.php?id=2934&type=98&tx_ttnews=306073[dead link]
- http://inpublic.globenewswire.com/2014/10/23/Novartis+AIN457+secukinumab+meets+primary+endpoint+in+two+Phase+III+studies+in+ankylosing+spondylitis+a+debilitating+joint+condition+of+the+spine+HUG1864939.html
- http://www.medpagetoday.com/MeetingCoverage/ACR/48743
- http://www.medscape.com/viewarticle/806510_6
- http://www.ncbi.nlm.nih.gov/pubmed/23361084
- http://clinicaltrials.gov/show/NCT01874340
| Monoclonal antibody | |
|---|---|
| Type | Whole antibody |
| Source | Human |
| Target | IL17A |
| Clinical data | |
| Legal status |
|
| Identifiers | |
| CAS number |  |
| ATC code | L04AC10 |
| DrugBank | DB09029 |
| Synonyms | AIN457 |
| Chemical data | |
| Formula | C6584H10134N1754O2042S44 |
| Molecular mass | 147.94 kDa |
FDA Approves Blincyto (blinatumomab) for Precursor B-Cell Acute Lymphoblastic Leukemia
Blinatumomab linking a T cell to a malignant B cell.
FDA Approves Blincyto (blinatumomab) for Precursor B-Cell Acute Lymphoblastic Leukemia
December 3, 2014 — The U.S. Food and Drug Administration today
approved Blincyto (blinatumomab) to treat patients with Philadelphia
chromosome-negative precursor B-cell acute lymphoblastic leukemia
(B-cell ALL), an uncommon form of ALL.
Blinatumomab (AMG103) is a drug that has anti-cancer properties. It belongs to a new class of constructed monoclonal antibodies,bi-specific T-cell engagers (BiTEs), that exert action selectively and direct the human immune system to act against tumor cells. Blinatumomab specifically targets the CD19 antigen present on B cells.[1]
The drug was developed by a German-American company Micromet, Inc. in cooperation with Lonza; Micromet was later purchases by Amgen, which has furthered the drug’s clinical trials. In July 2014, the FDA granted breakthrough therapy status to blinatumomab for the treatment of acute lymphoblastic leukemia (ALL).[2] In October 2014, Amgen’s Biologics License Application for blinatumomab was granted priority review designation by the FDA, thus establishing a deadline of May 19, 2015 for completion of the FDA review process.[3]
Structure and mechanism of action
Blinatumomab linking a T cell to a malignant B cell.
Blinatumomab enables a patient’s T cells to recognize malignant B cells. A molecule of blinatumomab combines two binding sites: a CD3site for T cells and a CD19 site for the target B cells. CD3 is part of the T cell receptor. The drug works by linking these two cell types andactivating the T cell to exert cytotoxic activity on the target cell.[4] CD3 and CD19 are expressed in both pediatric and adult patients, making blinatumomab a potential therapeutic option for both pediatric and adult populations.[5]
Therapeutic use
Clinical trials
In a phase 1 clinical study with blinatumomab, patients with non-Hodgkin’s lymphoma showed tumor regression, and in some cases complete remission.[6] There are ongoing phase 1 and phase 2 clinical trials of blinatumomab in patients with acute lymphoblastic leukemia (ALL).[7] One phase II trial for ALL reported good results in 2010 and another is starting.[8]
Adverse effects
Common side effects observed in Phase 2 trials are listed below; they were temporary and typically occurred during the first treatment cycle:[5]
- Flu-like symptoms (i.e. fever, headache, and fatigue)
- Tremor
- Weight increase
- Hypokalemia
- Decrease of blood immunoglobulin
CNS effects were also observed during clinical trials and were treated via a lower dose of blinatumomab, administration of dexamethasone, or treatment discontinuation. Because the side effects were reversible, early monitoring for the CNS symptoms listed below is important:[5]
- Seizure
- Encephalopathy
- Tremor
- Apraxia
- Speech disorders
- Disorientation
Less common side effects include cytokine release syndrome and immunogenicity.[5]
References
- Statement on a Nonproprietary Name adopted by the USAN Council: Blinatumomab
- Amgen Receives FDA Breakthrough Therapy Designation For Investigational BiTE® Antibody Blinatumomab In Acute Lymphoblastic Leukemia
- Amgen’s BiTE® Immunotherapy Blinatumomab Receives FDA Priority Review Designation In Acute Lymphoblastic Leukemia
- Mølhøj, M; Crommer, S; Brischwein, K; Rau, D; Sriskandarajah, M; Hoffmann, P; Kufer, P; Hofmeister, R; Baeuerle, PA (March 2007). “CD19-/CD3-bispecific antibody of the BiTE class is far superior to tandem diabody with respect to redirected tumor cell lysis”. Mol Immunol 44 (8): 1935–43. doi:10.1016/j.molimm.2006.09.032. PMID 17083975.
- Background Information for the Pediatric Subcommittee of the Oncologic Drugs Advisory Committee Meeting 04 December 2012
- Bargou, R; et al. (2008). “Tumor regression in cancer patients by very low doses of a T cell-engaging antibody”. Science 321 (5891): 974–977. doi:10.1126/science.1158545.PMID 18703743.
- ClinicalTrials.gov NCT00560794 Phase II Study of the BiTE Blinatumomab (MT103) in Patients With Minimal Residual Disease of B-precursor Acute ALL
- “Micromet initiates MT103 phase 2 trial in adult ALL patients”. 20 Sep 2010.
External links
| Monoclonal antibody | |
|---|---|
| Type | Bi-specific T-cell engager |
| Source | Mouse |
| Target | CD19, CD3 |
| Clinical data | |
| Legal status |
?
|
| Identifiers | |
| CAS number | 853426-35-4  |
| ATC code | None |
| UNII | 4FR53SIF3A |
| Chemical data | |
| Formula | C2367H3577N649O772S19 |
| Mol. mass | 54.1 kDa |
Glenmark’s Enrollment Begins of First Patient in Phase II Vatelizumab (GBR 500) Trial in Relapsing Remitting Multiple Sclerosis
Enrollment Begins of First Patient in Phase II Vatelizumab Trial in Relapsing Remitting Multiple Sclerosis
Glenmark outlicensed Vatelizumab (GBR 500) to Sanofi for all indications in 2011
Mumbai – India, November 4, 2014: Glenmark announced today enrollment of the first patient in a multicenter Phase II clinical trial to evaluate Genzyme’s investigational infusion therapy vatelizumab in patients with relapsing remitting multiple sclerosis (RRMS). The trial, called EMPIRE, is designed to assess the efficacy of vatelizumab vs. placebo in RRMS patients. The safety, tolerability and pharmacokinetics of vatelizumab will also be assessed.
read at
The mechanism of action of vatelizumab, which is developed in a collaboration between Glenmark Pharmaceuticals and Genzyme, is not yet fully understood. However, the researchers believe that it will be able to block VLA-2 on activated immune cells, which may enable the interference with collagen-binding in areas of inflammation, as well as leading to the reduction of inflammatory cascade associated with MS.
“We are excited about the commencement of this trial and are pleased with the continued progress of our partnership with Sanofi/Genzyme,” said the President of Biologics and Chief Scientific Officer of Glenmark Pharmaceuticals Ltd., Michael Buschle. EMPIRE, which will be conducted for 12 weeks, is a global phase 2a/2b double-blind, randomized, placebo-controlled study that will study the efficacy, safety, and dose-response of vatelizumab in 168 patients with active RRMS at55 sites in ten different countries.
Vatelizumab is an immunomodulator. It binds to integrin alpha 2.[1]
| Company | Glenmark Pharmaceuticals Ltd. |
| Description | mAb against integrin alpha(2) (VLA-2; CD49B) |
| Molecular Target | Integrin alpha(2) (VLA-2) (CD49B) |
| Mechanism of Action | Antibody |
| Therapeutic Modality | Biologic: Antibody |
| Latest Stage of Development | Phase I/II |
| Standard Indication | Inflammatory bowel disease (IBD) |
| Indication Details | Treat inflammatory bowel disease (IBD); Treat ulcerative colitis (UC) |
| Regulatory Designation | |
| Partner |
References
- World Health Organization (2011). “International Nonproprietary Names for Pharmaceutical Substances (INN). Proposed INN: List 105”(PDF). WHO Drug Information 25 (2).
Over 700 biosimilars now in development worldwide: report
More than 700 follow-on biologic therapies are currently in development, and they are expected to account for around a quarter of the $100 billion-worth of sales stemming from off-patent biologic drugs by the end of this decade, according to new research.
read at
Amgen files ‘breakthrough’ leukaemia drug Blinatumomab (AMG103) in the US
Blinatumomab
Biotechnology giant Amgen has filed its investigational cancer immunotherapy blinatumomab in the US for the treatment of certain forms of acute lymphoblastic leukaemia (ALL).
Specifically, the Biologic License Application seeks approval to market the drug for patients with Philadelphia-negative (Ph-) relapsed/refractory B-precursor forms of the aggressive blood/bone marrow cancer.
Blinatumomab (AMG103) is a drug that has anti-cancer properties. It belongs to a new class of constructed monoclonal antibodies, bi-specific T-cell engagers (BiTEs), that exert action selectively and direct the human immune system to act against tumor cells. Blinatumomab specifically targets the CD19 antigen present on B cells.[1]
The drug was developed by a German-American company Micromet, Inc. in cooperation with Lonza; Micromet was later purchases byAmgen, which has furthered the drug’s clinical trials.
Structure and mechanism of action
Blinatumomab linking a T cell to a malignant B cell.
Blinatumomab enables a patient’s T cells to recognize malignant B cells. A molecule of blinatumomab combines two binding sites: a CD3 site for T cells and a CD19 site for the target B cells. CD3 is part of the T cell receptor. The drug works by linking these two cell types and activating the T cell to exert cytotoxic activity on the target cell.[2]
Therapeutic use
Clinical trials
In a phase 1 clinical study with blinatumomab, patients with non-Hodgkin’s lymphoma showed tumor regression, and in some cases completeremission.[3] There are ongoing phase 1 and phase 2 clinical trials of blinatumomab in patients with acute lymphoblastic leukemia (ALL),[4]lung or gastrointestinal cancers.[citation needed] One phase II trial for ALL reported good results in 2010 and another is starting.[5]
| Monoclonal antibody | |
|---|---|
| Type | Bi-specific T-cell engager |
| Source | Mouse |
| Target | CD19, CD3 |
| Clinical data | |
| Legal status |
?
|
| Identifiers | |
| CAS number | 853426-35-4 |
| ATC code | None |
| UNII | 4FR53SIF3A |
| Chemical data | |
| Formula | C2367H3577N649O772S19 |
| Mol. mass | 54.1 kDa |
References
- Statement on a Nonproprietary Name adopted by the USAN Council: Blinatumomab
- Mølhøj, M; Crommer, S; Brischwein, K; Rau, D; Sriskandarajah, M; Hoffmann, P; Kufer, P; Hofmeister, R; Baeuerle, PA (March 2007). “CD19-/CD3-bispecific antibody of the BiTE class is far superior to tandem diabody with respect to redirected tumor cell lysis”. Mol Immunol 44 (8): 1935–43. doi:10.1016/j.molimm.2006.09.032. PMID 17083975.
- Bargou, R; et al. (2008). “Tumor regression in cancer patients by very low doses of a T cell-engaging antibody”. Science 321 (5891): 974–977. doi:10.1126/science.1158545.PMID 18703743.
- ClinicalTrials.gov NCT00560794 Phase II Study of the BiTE Blinatumomab (MT103) in Patients With Minimal Residual Disease of B-precursor Acute ALL
- “Micromet initiates MT103 phase 2 trial in adult ALL patients”. 20 Sep 2010.
External links
MAKE IN INDIA
http://makeinindia.com/
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Ibritumomab tiuxetan
Ibritumomab tiuxetan, sold under the trade name Zevalin, is a monoclonal antibody radioimmunotherapy treatment for relapsed or refractory, low grade or transformed B cell non-Hodgkin’s lymphoma, a lymphoproliferative disorder. The drug uses the monoclonal mouse IgG1 antibody ibritumomab (pronounced as <ih bri TYOO mo mab>)[1] in conjunction with the chelator tiuxetan, to which a radioactive isotope (either yttrium-90 or indium-111) is added. Tiuxetan is a modified version of DTPA whose carbon backbone contains an isothiocyanatobenzyl and a methyl group.[2][3]
Mechanism of action
The antibody binds to the CD20 antigen found on the surface of normal and malignant B cells (but not B cell precursors), allowing radiation from the attached isotope (mostly beta emission) to kill it and some nearby cells. In addition, the antibody itself may trigger cell death via antibody-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and apoptosis. Together, these actions eliminate B cells from the body, allowing a new population of healthy B cells to develop from lymphoid stem cells.
Zevalin (Ibritumomab tiuxetan) is a radio-labeled antibody. The antibody seeks and binds to cells that have a receptor called CD20 — present on both normal and malignant mature b-cells.
Once bound to the target cells, Zevalin delivers radiation, which enhances the killing effect of the antibody.
Because immature b-cells do not have the CD20 receptor, normal b-cells will recover in about nine months after treatment.
Rituxan (the naked antibody) is administered prior to Zevalin with the goal of clearing the majority of normal b-cells so that the therapeutic dose (the radio-labeled antibody) is more focused on tumor cells.
Preparation
Zevalin is supplied as a single dosage kit supplied by IDEC Pharmaceuticals Corp. It consists of Ibritumomab covalently conjugated to the metal chelator tiuxetan, which forms a stable complex with indium-111 for imaging and yttrium-90 for therapy.
The kit is supplied with four vials – a vial containing 3.2 mg of conjugated antibody in 2 ml saline, a vial containing 2 ml 50mM sodium acetate, a vial containing phosphate buffer, and a fourth empty reaction vial. Prior to labeling, a volume of sodium acetate buffer equivalent to 1.2 times the volume of the tracer solution is transferred to the reaction vial. Then 5.5 mCi (203.5 MBq) indium-111 or 40mCi (1.48 GBq) yttrium-90 is added to the reaction vial and mixed thoroughly without shaking. Next, 1.3 ml of conjugated antibody is added. The mixture is incubated for exactly 30min for indium-111 and for 5 min with yttrium-90 labeling, followed by the addition of enough phosphate buffer to make the final volume 10 ml. The labeling yield is determined by ITLC-SG with 0.9% saline as the mobile phase. Labeling efficiency should be greater than 95%.[4]
http://pubs.rsc.org/en/content/articlelanding/2006/cs/b514859f/unauth#!divAbstract
A cartoon depiction of the radiolabelled monoclonal antibody 90Y-ibritumomab tiuxetan 18.
Administration
In order to qualify for ibritumomab, a patient needs to have bone marrow involvement of < 25% and > 15% bone marrow cellularity. Since ibritumomab is known to cause cytopenia, platelet and neutrophil counts are also taken pretreatment. Refractory/relapsed patients should have platelet counts of 100,000 per cubic millimetre (100,000/cmm) or greater; consolidation patients should have counts of 150,000/cmm or greater. Since a murine antibody is used, the patient might also be tested for human anti mouse antibodies (HAMA). Having bulky disease does not disqualify a patient.
The ibritumomab regimen takes 7–9 days. An imaging dose of the drug is no longer required in the U.S. Rituxan 250 mg/sq.m is given day 1, then on day 7-9 the Rituxan dose is repeated and Zevalin given within four hours. The dose of Zevalin 0.4 mCi/kg (= 14.8MBq/kg) if platelet counts are above 150,000/cmm; 0.3 mCi/kg (= 11.1MBq/kg) if 100,000-150,000/cmm. The Zevalin dose never exceeds 32 mCi (= 1184MBq).[5]
Ibritumomab tiuxetan is administered by intravenous infusion which usually lasts around 10 minutes. Only acrylic shielding is needed, not lead. A trained nuclear medicine technologist performs the infusion and safely disposes of waste.
Efficacy
Treatment with ibritumomab showed higher response rates in clinical trials compared to treatment with only rituximab (similar to ibritumomab, but without the attached radioisotope), and showed very promising results for patients who no longer respond to rituximab.
In patients with relapsed or refractory low-grade, follicular, or transformed B-cell NHL, where no prior anti-CD20 therapy was allowed, the ORR was 83% / 55% and CR was 38% / 18%, comparing ibritumomab to rituximab. [6]
Recently, extended follow-up data for the ZEVALIN ([90Y]-ibritumomab tiuxetan) First-line Indolent (FIT) study presented at the American Society of Hematology (ASH) Annual Meeting demonstrated the continued improvement in progression-free survival (PFS) following ibritumomab consolidation therapy for patients with follicular B-cell non-Hodgkin’s lymphoma who achieved a response to first-line therapy over chemotherapy alone. Additionally, ibritumomab consolidation did not adversely affect the use of various effective second-line treatments including stem cell transplants in patients who relapsed.[7]
In a Phase II study on patients with relapsed and refractory mantle cell lymphoma, the OR was 42% and CR was 26%.[8]
A study demonstrated that rituximab followed by single agent ibritumomab in a front-line setting for patients with MALT lymphoma and low-grade follicular lymphoma that primarily involved the conjunctiva or orbit, produced a complete response rate of 83 percent.[9]
http://rd.springer.com/article/10.2165%2F00024669-200201050-00004#page-1
History
Developed by the IDEC Pharmaceuticals, which is now part of Biogen Idec, ibritumomab tiuxetan was the first radioimmunotherapy drug approved by the Food and Drug Administration (FDA) in 2002 to treat cancer. It was approved for the treatment of patients with relapsed or refractory, low‑grade or follicular B‑cell non‑Hodgkin’s lymphoma (NHL), including patients with rituximab refractory follicular NHL.
In December 2007, Cell Therapeutics Inc acquired the U.S. rights to sell, market, and distribute this radioimmunotherapy antibody from Biogen for approximately US$30 million, or the equivalent of about two years’ net sales revenue in the U.S. for the drug.[10] Outside of the U.S., Bayer Schering Pharma continues to have the rights to the drug.
In March 2009, Spectrum Pharmaceuticals acquired 100% control of RIT Oncology, LLC, to commercialize Zevalin in the US. Now Spectrum Pharmaceuticals is responsible for all activities relating to Zevalin in the US.
In September 2009, ibritumomab received approval from the FDA for an expanded label for the treatment of patients with previously untreated follicular non-Hodgkin’s Lymphoma (NHL), who achieve a partial or complete response to first-line chemotherapy.
Costs
Ibritumomab which is not available in a generic form because it is still under patent protection, is currently the most expensive drug available given in a single dose, costing over US$ 37,000 (€ 30,000) for the average dose. However, ibritumomab is essentially an entire course of lymphoma therapy which is delivered in 7–9 days, with one visit for pre-dosing Rituxan, and one visit a week later for the actual Zevalin therapeutic dose preceded by Rituxan. Compared to other monoclonal antibody treatments (many of which are well over US$ 40,000 for a course of therapy), this drug is priced in the middle for many of these therapies.
 |
|
| Monoclonal antibody | |
|---|---|
| Type | Whole antibody |
| Source | Mouse |
| Target | CD20 |
| Clinical data | |
| Trade names | Zevalin |
| AHFS/Drugs.com | monograph |
| Licence data | US FDA:link |
| Legal status | |
| Routes | intravenous |
| Identifiers | |
| CAS number | 174722-31-7 |
| ATC code | V10XX02 (90Y) |
| DrugBank | DB00078 |
External links
- http://www.zevalin.com/ – Official Zevalin web site
- http://www.spectrumpharm.com/ – Spectrum Pharmaceuticals, Inc. web site
- http://www.accessdata.fda.gov/drugsatfda_docs/label/2002/ibriide021902LB.pdf – Package Insert
http://www.fda.gov/ohrms/dockets/ac/01/slides/3782s2_02_idec/sld015.htm
References
- Ibritumomab: Pronunciation
- Milenic, Diane E.; Brady, Erik D.; Brechbiel, Martin W. (June 2004). “Antibody-targeted radiation cancer therapy”. Nat Rev Drug Discov 3 (6): 488–499. doi:10.1038/nrd1413. ISSN 1474-1776. PMID 15173838.
- WHO Drug Information
- http://www.accessdata.fda.gov/drugsatfda_docs/label/2002/ibriide021902LB.pdf
- Ibritumomab: Indications
- Ibritumomab: Efficacy
- ZEVALIN Consolidation in First-Line Therapy in Patients with Non-Hodgkin’s Lymphoma Resulted in a Progression-Free Survival of Greater Than 67 Months
- Zevalin and mantle cell
- ZEVALIN(R) Produced 83 Percent Complete Response Rate in Mucosa-Associated Lymphoid Tissue (MALT) Orbital Lymphoma Study
- [1]
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September 23, 2014
// CASI Signs China Licensing Deal With Spectrum For 3 Cancer Drugs…http://www.outsourcedpharma.com/doc/casi-signs-china-licensing-deal-with-spectrum-for-cancer-drugs-0001
// CASI Signs China Licensing Deal With Spectrum For 3 Cancer Drugs// // // // //
CASI Pharmaceuticals and Spectrum Pharmaceuticals (SPPI) announced the signing of a license agreement that gives CASI exclusive rights to develop three cancer drugs from Spectrum and market them in China, including Macau, Hong Kong, and Taiwan.
The agreement concerns the two approved cancer drugs Zevalin (ibritumomab tiuxetan) Injection non-Hodgkin’s lymphoma (NHL) and Marqibo (vinCRIStine sulfate LIPOSOME injection) for acute lymphoblastic leukemia (ALL) as well as the investigational Phase 3 drug Captisol-Enabled Melphalan (CE melphalan) being studied as a conditioning treatment before autologous stem cell transplant in patients with multiple myeloma. Spectrum recently reported that Melphalan met its primary endpoint in its pivotal safety and efficacy trial. In view of the results, Spectrum said it intends to file a New Drug Application (NDA) with the U.S. Food and Drug Administration (FDA) for the drug in the second half of 2014.
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Sun Pharma, Merck & Co Inc ink pact for Tildrakizumab
Sep 17, 2014,
Under terms of the agreement, Sun Pharma will acquire worldwide rights to tildrakizumab for use in all human indications from Merck in exchange for an upfront payment of USD 80 million.
Pharma major Sun Pharmaceutical Industries today entered into a licensing agreement with Merck & Co Inc for investigational therapeutic antibody candidate, tildrakizumab to be used for treatment of plaque psoriasis. Under terms of the agreement, Sun Pharma will acquire worldwide rights to tildrakizumab for use in all human indications from Merck in exchange for an upfront payment of USD 80 million, the companies said in a joint statement. Tildrakizumab is being evaluated in Phase III registration trials for the treatment of chronic plaque psoriasis, a skin ailment. “Merck will continue all clinical development and regulatory activities, which will be funded by Sun Pharma. Upon product approval, Sun Pharma will be responsible for regulatory activities, including subsequent submissions, pharmacovigilance, post approval studies, manufacturing and commercialisation of the approved product,” it added.
Sun Pharma managing director Dilip Shanghvi.
| Monoclonal antibody | |
|---|---|
| Source | Humanized (from mouse) |
| Target | IL23 |
| Clinical data | |
| Legal status |
?
|
| Identifiers | |
| CAS number | 1326244-10-3 |
| ATC code | None |
| Chemical data | |
| Formula | C6426H9918N1698O2000S46 |
| Mol. mass | 144.4 kDa |
Tildrakizumab is a monoclonal antibody designed for the treatment of immunologically mediated inflammatory disorders.[1]
Tildrakizumab was designed to block interleukin-23, a cytokine that plays an important role in managing the immune system andautoimmune disease. Originally developed by Schering-Plough, this drug is now part of Merck‘s clinical program, following that company’s acquisition of Schering-Plough.
As of March 2014, the drug was in phase III clinical trials for plaque psoriasis. The two trials will enroll a total of nearly 2000 patients, and preliminary results are expected in June, 2015. [2][3]
New Drug Approvals 
