New Drug Approvals

Home » Monoclonal antibody » Health Canada Approves ADCETRIS® (Brentuximab Vedotin) for the Treatment of Relapsed or Refractory Hodgkin Lymphoma (HL) and Systemic Anaplastic Large Cell Lymphoma (sALCL)

Health Canada Approves ADCETRIS® (Brentuximab Vedotin) for the Treatment of Relapsed or Refractory Hodgkin Lymphoma (HL) and Systemic Anaplastic Large Cell Lymphoma (sALCL)

DRUG APPROVALS BY DR ANTHONY MELVIN CRASTO .....FOR BLOG HOME CLICK HERE

PAYPAL DONATIONS

ORGANIC SPECTROSCOPY

Read all about Organic Spectroscopy on ORGANIC SPECTROSCOPY INTERNATIONAL 

Categories

Blog Stats

  • 1,309,758 hits

Enter your email address to follow this blog and receive notifications of new posts by email.

Join 1,782 other followers

add to any

Share

Seattle and Millennium Report 75% Response Rate in Pivotal ADC Hodgkin Lymphoma Trial

C) brentuximab vedotin. An ADC is a three-block “engine” -- antibody-linker-drug -- and each part of the composite molecule has to be carefully selected and assembled. Considered as an armed-antibody, an ADC is a bi-dentate construction where both parts (antibody and drug) of the molecule combine their effect to ensure selectivity and potency. The role of the linker arm is of paramount importance demanding a fine tuning to execute the controlled release and delivery of the two active components in the tumor environment.

 Structure of brentuximab vedotin

Brentuximab vedotin on track for BLA filing with FDA during first half of 2011. [© Sebastian Kaulitzki – Fotolia.com]

Brentuximab is a human antibody. The antibody portion of Brentuximab vedotin has the sequence of two copies of:

>Brentuximab vedotin - heavy chain
QIQLQQSGPEVVKPGASVKISCKASGYTFTDYYITWVKQKPGQGLEWIGWIYPGSGNTKY
NEKFKGKATLTVDTSSSTAFMQLSSLTSEDTAVYFCANYGNYWFAYWGQGTQVTVSAAST 
KGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY 
SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSV 
FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY 
RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTK
NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQG 
NVFSCSVMHEALHNHYTQKSLSLSPG
>Brentuximab vedotin - light chain
DIVLTQSPASLAVSLGQRATISCKASQSVDFDGDSYMNWYQQKPGQPPKVLIYAASNLES 
GIPARFSGSGSGTDFTLNIHPVEEEDAATYYCQQSNEDPWTFGGGTKLEIKRTVAAPSVF 
IFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLS 
STLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

February 01, 2013

Seattle Genetics, Inc.  today announced that Health Canada has issued a Notice of Compliance with conditions (NOC/c), authorizing marketing of ADCETRIS for two lymphoma indications: (1) the treatment of patients with Hodgkin lymphoma (HL) after failure of autologous stem cell transplant (ASCT) or after failure of at least two multi-agent chemotherapy regimens in patients who are not ASCT candidates, and (2) the treatment of patients with systemic anaplastic large cell lymphoma (sALCL) after failure of at least one multi-agent chemotherapy regimen. The indications for ADCETRIS were authorized based on promising response rates demonstrated in single-arm trials. No data demonstrate increased survival with ADCETRIS.

“they are focused on making ADCETRIS available globally to all eligible patients with relapsed HL and sALCL. The approval of ADCETRIS in Canada, as well as the recent approval in the European Union, are important milestones to accomplish this goal,” said Clay B. Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics. “Now that Health Canada has approved ADCETRIS, we are committed to working closely with public and private insurers to secure reimbursement coverage for patients in Canada.”

“The approval of ADCETRIS in Canada marks a significant milestone for patients with relapsed HL or sALCL who have had few new treatment options in several decades,” Joseph M. Connors, M.D., FRCPC, Clinical Director, Center for Lymphoid Cancer at BC Cancer Agency in Vancouver, Canada.

Health Canada grants NOC/c, a form of market approval, on the basis of promising evidence of clinical effectiveness, for products intended for the treatment of serious, life-threatening or severely debilitating illnesses that meet a serious unmet medical need or demonstrate a significant improvement in the benefit/risk profile over existing therapies. Conditions associated with market authorization under the NOC/c policy include a requirement that Seattle Genetics conduct clinical trials designed to confirm the anticipated clinical benefit of ADCETRIS in these patients. Two confirmatory phase III clinical trials evaluating ADCETRIS in the front-line treatment setting of HL and mature T-cell lymphoma (MTCL), including sALCL, are currently underway and enrolling patients.

ADCETRIS (brentuximab vedotin) was issued marketing authorization under the NOC/c policy based on results from a single-arm, phase II pivotal trial in HL patients with relapsed or refractory disease following an ASCT and a single-arm, phase II pivotal trial in relapsed or refractory sALCL patients. ADCETRIS is administered in hospitals through IV infusion over 30 minutes every three weeks and patients who achieve stable disease or better should receive a minimum of 8 cycles and up to a maximum of 16 cycles (approximately one year).

ADCETRIS is the first in a new class of antibody-drug conjugates (ADCs) to be approved in Canada. Using Seattle Genetics’ proprietary technology, the ADC consists of a monoclonal antibody directed to an antigen called CD30. The monoclonal antibody is connected to a cell-killing agent by a linker system that is designed to be stable in the bloodstream but to release the cell-killing agent into CD30-expressing cells, resulting in target cell death. The CD30 antigen is known to be expressed on the Reed-Sternberg cells of HL and on sALCL, an aggressive type of T-cell non-Hodgkin lymphoma.

“Health Canada’s approval of ADCETRIS is the first step in getting patients access to this important therapy,” said Sue Robson, Executive Director of Lymphoma Foundation Canada. “The Lymphoma Foundation is committed to working with Canada provincial governments to ensure that appropriate patients have access to this new therapy.”

About Lymphoma

Lymphoma is a general term for a group of cancers that originate in the lymphatic system. There are two major categories of lymphoma: Hodgkin lymphoma and non-Hodgkin lymphoma. Hodgkin lymphoma is distinguished from other types of lymphoma by the presence of one characteristic type of cell, known as the Reed-Sternberg cell. The Reed-Sternberg cell generally expresses CD30. Systemic ALCL is an aggressive type of T-cell non-Hodgkin lymphoma that also expresses CD30.

Brentuximab vedotin (INN, codenamed SGN-35 and previously cAC10-vcMMAE) is an antibody-drug conjugate approved to treat anaplastic large cell lymphoma (ALCL) and Hodgkin lymphoma. The U.S. Food and Drug Administration granted the agent an accelerated approval on August 19, 2011 for use against these two diseases.[1] It is marketed as Adcetris.[2]

The compound consists of the chimeric monoclonal antibody brentuximab (which targets the cell-membrane protein CD30) linked to three to five units of the antimitotic agent monomethyl auristatin E (MMAE, reflected by the ‘vedotin’ in the drug’s name). The antibody portion of the drug attaches to CD30 on the surface of malignant cells, delivering MMAE which is responsible for the anti-tumour activity.[3][4] Hence it is an antibody-drug conjugate.

In a 2010 clinical trial,[5] 34% of patients with refractory Hodgkin Lymphoma achieved complete remission and another 40% had partial remission.[6] Tumor reductions were achieved in 94% of patients. In ALCL, 87% of patients had tumors shrink at least 50% and 97% of patients had some tumors shrinkage.[7]

On 28 February 2011 a Biologics License Application (BLA) was submitted to the U.S. Food and Drug Administration (FDA) for the use of brentuximab vedotin in relapsed or refractory Hodgkin’s lymphoma and relapsed or refractory systemic anaplastic large cell lymphoma.[8] Both indications were approved by the FDA in Aug 2011.[9]

For these same indications brentuximab vedotin received a conditional Marketing authorization from the European Medicines Agency in october 2012.[10]

  1. FDA: Brentuximab Vedotin
  2.  Seattle Genetics to Present Brentuximab Vedotin and SGN-75 Clinical Data at the American Society of Clinical Oncology Annual Meeting
  3.  Seattle Genetics: Brentuximab vedotin (SGN-35)
  4. Francisco, Joseph A; et al. (2003). “cAC10-vcMMAE, an anti-CD30–monomethyl auristatin E conjugate with potent and selective antitumor activity”. Blood 102 (4): 1458–1465. doi:10.1182/blood-2003-01-0039. PMID 12714494.
  5. ClinicalTrials.gov NCT00848926 A Pivotal Open-Label Trial of SGN-35 for Hodgkin Lymphoma
  6. “Seattle Genetics and Millennium Report Positive Data from Pivotal Trial of Brentuximab Vedotin (SGN-35) in Relapsed or Refractory Hodgkin Lymphoma at ASH Annual Meeting”. Dec 2010.
  7.  “Is Seattle Genetics the Next Big Thing?”. 2 Dec 2010.
  8.  “Seattle Genetics Submits BLA to FDA for Brentuximab Vedotin in Relapsed or Refractory Hodgkin Lymphoma and Systemic ALCL”. 28 Feb 2011.
  9. Genetic Engineering & Biotechnology News: Seattle Genetics’ Antibody-Drug Conjugate Receives FDA Okay to Treat Lymphomas
  10.  http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Summary_for_the_public/human/002455/WC500135004.pdf

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s

Paypal Donate

DR ANTHONY CRASTO

Follow New Drug Approvals on WordPress.com

Enter your email address to follow this blog and receive notifications of new posts by email.

Join 1,782 other followers

DR ANTHONY MELVIN CRASTO Ph.D

DR ANTHONY MELVIN CRASTO Ph.D

DR ANTHONY MELVIN CRASTO, Born in Mumbai in 1964 and graduated from Mumbai University, Completed his Ph.D from ICT, 1991,Matunga, Mumbai, India, in Organic Chemistry, The thesis topic was Synthesis of Novel Pyrethroid Analogues, Currently he is working with GLENMARK PHARMACEUTICALS LTD, Research Centre as Principal Scientist, Process Research (bulk actives) at Mahape, Navi Mumbai, India. Total Industry exp 29 plus yrs, Prior to joining Glenmark, he has worked with major multinationals like Hoechst Marion Roussel, now Sanofi, Searle India Ltd, now RPG lifesciences, etc. He has worked with notable scientists like Dr K Nagarajan, Dr Ralph Stapel, Prof S Seshadri etc, He did custom synthesis for major multinationals in his career like BASF, Novartis, Sanofi, etc., He has worked in Discovery, Natural products, Bulk drugs, Generics, Intermediates, Fine chemicals, Neutraceuticals, GMP, Scaleups, etc, he is now helping millions, has 9 million plus hits on Google on all Organic chemistry websites. His friends call him worlddrugtracker. His New Drug Approvals, Green Chemistry International, All about drugs, Eurekamoments, Organic spectroscopy international, etc in organic chemistry are some most read blogs He has hands on experience in initiation and developing novel routes for drug molecules and implementation them on commercial scale over a 29 year tenure till date Aug 2016, Around 30 plus products in his career. He has good knowledge of IPM, GMP, Regulatory aspects, he has several International patents published worldwide . He has good proficiency in Technology transfer, Spectroscopy, Stereochemistry, Synthesis, Polymorphism etc., He suffered a paralytic stroke/ Acute Transverse mylitis in Dec 2007 and is 90 %Paralysed, He is bound to a wheelchair, this seems to have injected feul in him to help chemists all around the world, he is more active than before and is pushing boundaries, He has 9 million plus hits on Google, 2.5 lakh plus connections on all networking sites, 25 Lakh plus views on dozen plus blogs, He makes himself available to all, contact him on +91 9323115463, email amcrasto@gmail.com, Twitter, @amcrasto , He lives and will die for his family, 90% paralysis cannot kill his soul., Notably he has 13 lakh plus views on New Drug Approvals Blog in 212 countries......https://newdrugapprovals.wordpress.com/ , He appreciates the help he gets from one and all, Friends, Family, Glenmark, Readers, Wellwishers, Doctors, Drug authorities, His Contacts, Physiotherapist, etc

Personal Links

View Full Profile →

TWITTER

bloglovin

Follow my blog with Bloglovin The title of your home page You could put your verification ID in a comment Or, in its own meta tag Or, as one of your keywords Your content is here. The verification ID will NOT be detected if you put it here.
%d bloggers like this: