Farletuzumab ( Eisai) Cancer Review

Farletuzumab ( Eisai) Cancer Review

Monoclonal antibody to treat ovarian cancer
Farletuzumab (Morphotek, Eisai) is an antifolate receptor alpha mAbs in clinical Phase III trials in ovarian cancer patients. The results of the Phase II trials for advanced ovarian cancer patients not yet published. Interim results indicated durable objective response justifying the need for a Phase III trial. Eisai has provided updated info during the 3Q2010 R&D review of key projects. Farletuzumab is expected to show activity in cancer types which overexpress Folate receptor alpha such as ovarian, breast, colorectal, NSCLC, RCC etc. Phase II study in platinum sensitive ovarian cancer, confirmed extended recurrence period in 21% of patients. The multicentric multinational Phase III study in Pt sensitive ovarian cancer in ongoing and results expected by the end of 2011. BLA/MAA filings planned for 2012. Phase II trials in Pt resistant ovarian cancer and NSCLC are ongoing. New data may be presented during the ASCO 2011 meeting.
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The article discusses many unapproved, unlabeled and unevaluated uses/indications of  products
 under clinical investigation which have not been approved or reviewed by the FDA/EMA. Farletuzumab has not been reviewed or approved by the FDA/EMA.




Introduction                                                                                                        


The over expression of folate receptor alpha in ovarian cancer and its association with aggressive forms of cancer makes this receptor a target of Farlutuzumab . Fmab (MORAb-003) was discovered and developed by Morphotek which after its takeover operates as a subsidiary of Eisai. 


Nomenclature
Prefix Sub stem A Sub stem B Suffix common
Farle tu zu mab
Innovator choice tumor humanized monoclonal antibody





Farletuzumab is a humanized monoclonal antibody for cancer treatment.

The mAbs is in Phase II trials in ovarian cancer patients resistant to platinum drugs. It is Phase III trials in platinum sensitive ovarian cancer patients after their first relapse.

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Morphotek Eisai                                                                                                


Image from Morphotek



Morphotek discovered a clever way of making human or humanized mAbs using the natural deletion mechanism ( morphogenics ) of eliminating dangerous mutations through mismatch repair.




The company used morphogenics for the following applications.

Generated human mAbs bypassing all the patents for recombinant technology. Human Morphodoma
and Libradoma to generate and screen to identify human mAbs to known antigens and bypass all existing technologies and patents. R&D deals with big pharma validate this approach like Amgen, J&J, Novo Nordisk and Pfizer. 

Because of its unique mAbs technology platform and its leads in development, Morphotek was taken over in 2007 by Eisai for $ 325 million, which by current prices looks very cheap. The takeover has added several mAbs to the parent company R&D portfolio and new regulatory filing and market introductions projected during 2013-2015 period. A monoclonal antibody MORAb-004 is in Phase 1 trials and targets a cell surface protein endosialin or tumor endothelial marker 1 TEM and CD248. MORAb-009 is in Phase II trials for pancreatic cancer and targets cell surface glycoprotein mesothelin. Farletuzumab is in Phase III trials with orphan drug designation.


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YouTube Video




Ovarian cancer                                                                                                   


There were 21000 new cases of ovarian cancer and 14600 deaths in the US in 2009. There are 65000 new cases worldwide each year.
 
Ovarian Cancer Home Page [3]

Ovarian Cancer  By Pedro [4]

For a recent review and new agents in development.[5][6][7]



Warning- Some of the graphic images and photos presented may hurt the sensibility of some persons and children . Such persons are advised to discontinue.

Under Creative Commons Attribution 3.0 License
Ovarian cancer dangers



http://www.nlm.nih.gov/medlineplus/ency/images/ency/fullsize/17106.jpg

YouTube Video




YouTube Video



Under Creative Commons Attribution 3.0 License
NCI CDR618030


Estrogen receptor assay
NCI Image ID 2028
preview



Cis Platinum Crystals

NCI Image ID 2313
 




Folate Pathway
http://sites.huji.ac.il/malaria/maps/folate.gif




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Farletuzumab                                                                                                     

 
Eisai has provided updated info during the 3Q2010 R&D review of key projects. Farletuzumab is expected to show activity in cancer types which overexpress Folate receptor alpha such as ovarian, breast, colorectal, NSCLC, RCC etc. Phase II study in platinum sensitive ovarian cancer, confirmed extended recurrence period in 21% of patients.  The multicentric multinational Phase III study in Pt sensitive ovarian cancer in ongoing and results expected by the end of 2011. BLA/MAA filings planned for 2012. Phase II trials in Pt resistant ovarian cancer and NSCLC are ongoing.
 
[8][9]

FAR-131-blue small


Safety and efficacy                                                                                             

Data not yet available in peer reviewed journals although it has been presented as abstracts in meetings.
 
ASCO 2010 Abstracts
 
 
 



 











Farletuzumab Clinical Trials

Farletuzumab Clinical Trials





Breaking News ASCO   2010                                                                                                       


Abstracts, new data and video presented at ASCO Meeting will be added in this section ASAP




#5001-Efficacy and safety of farletuzumab, a humanized monoclonal antibody to folate receptor alpha, in platinum-sensitive relapsed ovarian cancer subjects: Final data from a multicenter phase II study.
Allan J. White, MD

• Discussion: Targeting the folate receptor in ovarian cancer. (Please also note functional folate receptor imaging abstract 44469)
Alan Hilary Calvert, MD

Phase II data on 54  patients (pt sensitive after 1st relapse) treated with weekly injections of farletuzumab (q 21 d for 6 cycles) as a single agent or added to carboplatin or carboplatin and taxane. After 6 cycles of dosing, Fmab was given as maintenance dose. No additive toxicity was observed and Fmab was well tolerated. 44 patients evaluable, 89% of treated patients had normal CA 125 levels. Nine out of 44 patients had duration of their second remission lasting longer than the first remission.

Phase II trial ongoing in 126 ovarian cancer patients resistant to platinum to be enrolled and randomized in a 2:1 ratio with paclitaxel. The design of the study and protocol was presented at ASCO meeting.
  
45A #5034-Use of 99mTc-EC20 (a folate-targeted imaging agent) to predict response to therapy with EC145 (folate-targeted therapy) in advanced ovarian cancer.
James Thomas Symanowski

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Books and Monographs                                                                                                                

Breast, Ovarian and Cervical Cancer

Breast, Ovarian and Cervical Cancer



Live MED and R&D RSS Feeds                                                                            

These are given as examples. Live updates of Clinical trials, patents filed, patents published, slides, training manual, educational material, publications, abstracts, presentations can be provided for this product and its potential rival.



European Medicines Agency


What's New: Drugs RSS Feed



Farletuzumab Google News ‎(U.S.)‎

Farletuzumab Google News ‎(U.S.)‎

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Monoclonal Antibody Guide                                                                            


Monoclonal Antibody Guide, Knols

Monoclonal Antibody Guide, Knols




Acknowledgements                                                                            

 

Thanks are due to Mr. Jean-Antoine de Mandato (PDP, Geneva) for providing office facilities and administrative support.

 

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References

  1. http://www.morphotek.com/Uploads/DocumentRepository/Morphotek-Bioprocess%20Intl-11.04.pdf
  2. Li J, Sai T, Berger M, Chao Q, Davidson D, Deshmukh G, Drozdowski B, Ebel W, Harley S, Henry M, Jacob S, Kline B, Lazo E, Rotella F, Routhier E, Rudolph K, Sage J, Simon P, Yao J, Zhou Y, Kavuru M, Bonfield T, Thomassen MJ, Sass PM, Nicolaides NC, Grasso L. Human antibodies for immunotherapy development generated via a human B cell hybridoma technology. Proc Natl Acad Sci U S A. 2006 Mar 7;103(10):3557-62. Epub 2006 Feb 27. PubMed PMID: 16505368; PubMed Central PMCID: PMC1383494.
  3. http://www.cancer.gov/cancertopics/types/ovarian
  4. http://knol.google.com/k/ovarian-cancer#
  5. Hennessy BT. Coleman, RL. Markman M. Ovarian cancer. The Lancet, 2009 Oct 374: 9698, 1371-1382.
  6. Hennessy BT. Markman M. Development of novel agents for ovarian cancer. Update on Cancer Therapeutics, 2009, Apr. 3:3, 119-132.
  7. Willmott LJ, Fruehauf JP. Targeted therapy in ovarian cancer. J Oncol. 2010;2010:740472. Epub 2010 Jan 14. PubMed PMID: 20130818; PubMed Central PMCID: PMC2814233.
  8. Kalli KR. MORAb-003, a fully humanized monoclonal antibody against the folate receptor alpha, for the potential treatment of epithelial ovarian cancer. Curr Opin Investig Drugs. 2007 Dec;8(12):1067-73. PubMed PMID: 18058577.
  9. Smith-Jones PM, Pandit-Taskar N, Cao W, O'Donoghue J, Philips MD, Carrasquillo J, Konner JA, Old LJ, Larson SM. Preclinical radioimmunotargeting of folate receptor alpha using the monoclonal antibody conjugate DOTA-MORAb-003. Nucl Med Biol. 2008 Apr;35(3):343-51. PubMed PMID: 18355690; PubMed Central PMCID: PMC2676680.
  10. Armstrong DK. Coleman R. White AJ. Bicher, A. Gibbon DG. Old L. Verheijen R. Weil S. Phillips M. Chakrabarti D. 8000 Efficacy and safety of farletuzumab, a humanized monoclonal antibody to folate receptor alpha, in platinum-sensitive relapsed ovarian cancer subjects: preliminary data from a phase-2 study. Eur. J. Cancer Supplements. 2009, Sept 7:2, 450.
  11. Spannuth WA, Sood AK, Coleman RL. Farletuzumab in epithelial ovarian carcinoma. Expert Opin Biol Ther. 2010 Mar;10(3):431-7. PubMed PMID: 20092424.
  12. Ebel W, Routhier EL, Foley B, Jacob S, McDonough JM, Patel RK, Turchin HA, Chao Q, Kline JB, Old LJ, Phillips MD, Nicolaides NC, Sass PM, Grasso L. Preclinical evaluation of MORAb-003, a humanized monoclonal antibody antagonizing folate receptor-alpha. Cancer Immun. 2007 Mar 9;7:6. PubMed PMID: 17346028.

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