Replies to post #107258 on Biotech Values

[pollyvonwog]

DD has suggested that Teva is not the source of the generic Lovenox that they filed with the FDA

Just to clarify, TEVA IR has confirmed that TEVA is in fact not the source of generic lovenox so it is more than a suggestion.

[ilpapa]

But IF we find that the tL is already being marketed in South America or elsewhere

That would be interesting. Do we know that it is or may be?

[go seek]

Some of the generic versions of LMWHs are already available in Asia and South America and represent substandard products. These products do not conform to current product and regulatory compliance guidelines. For this reason some of the generic LMWHs manufactured in South Asia have been removed from the market. Moreover, there are no established guidelines to approve or disapprove these drugs in Europe or the US. Therefore, additional guidelines regarding the characterization of these products may be needed, and any unilateral claim from manufacturers that structural information obtained from specific analytical profiling may result in an ideal generic product is not valid. Claims from the suppliers that generic LMWHs are identical to branded products are not supported by any publication or other documentation that we are aware of at this time. Chemical characterization of a complex heterogeneous sulfated carbohydrate mixture may be similar; however, the pharmacodynamics of such a mixture is a cumulative biologic response. Until data on pharmacodynamics are available, the product(s) cannot be claimed similar. Therefore in addition to the chemical characterization, molecular profiling of these drugs may be necessary.

above is an excerpt from:
Generic Low Molecular Weight Heparins: Where Do We Stand?

http://www.natfonline.org/graphics/LMWHs_July2007.pdf

[turtlepower]

There's an ASH presentation comparing enox with cutenox.

http://ash.confex.com/ash/2010/webprogram/Paper31905.html

1086 An Open Label, Non Randomized, Propspective Phase IV Clinical Trial Evaluating the Immunogenicity of Branded Enoxaparin Versus Biosimilars In Healthy Volunteers
Oral and Poster Abstracts
Poster Session: Antithrombotic Therapy: Poster I
Saturday, December 4, 2010, 5:30 PM-7:30 PM
Hall A3/A4 (Orange County Convention Center)
Poster Board I-66
Marise Gomes, Ph.D.1*, Eduardo Ramacciotti, M.D., Ph.D.1*, Debra Hoppensteadt, Ph.D.2*, Jeanine M. Walenga, PhD3, Bruce E Lewis, MD4*, Walter Jeske, Ph.D.5* and Jawed Fareed, PhD2

1University of Michigan, Ann Arbor, MI
2Pathology and Pharmacology, Loyola University Chicago, Maywood, IL
3Cardiovascular Institute, Loyola Univ. Medical Center, Maywood, IL
4Cardiology, Loyola University Chicago, Maywood, IL
5Thoracic and Cardiovascular Surgery, Loyola University Medical Center, Maywood, IL

Biosimilar enoxaparin preparations are in use outside the U.S. Due to compositional variations, their interaction with platelet factor 4 (PF4) differs leading to differential immunogenic responses between branded and biosimilar agents. To compare their immunogenic response, branded enoxaparin (Clexane®, Sanofi-Aventis) and a biosimilar version (Cutenox®, Gland-Pharma) were administered to healthy volunteers (n=110/drug) at a dose of 40 mg SQ for10 days. Blood samples drawn on days 1 and 10 were analyzed for anti-heparin/PF4 antibody (A-HPF4-Ab) titers and subtypes by ELISA (GTI, Brookfield, WI). Treatment with each LMWH resulted in comparable A-HPF4-Ab generation as compared by using the total absorbance for each population (p<0.05). However in the thrombin generation assays clexane group showed a stronger inhibition (45+12% vs 32+9%). None of these antibodies activated platelets as determined by the serotonin release assay. The two groups alos showed comparable AXa and AIIa responses (p<0.05). Antibody subtyping demonstrated different profiles between LMWHs. For IgG (Clexane1=0.15±0.04, Clexane10=0.21±0.06, Cutenox1=0.17±0.04, Cutenox10=0.28±0.10) with a significant time effect (p<0.0001), a significant drug effect (p<0.0001), and a significant time by drug interaction (p=.0009). Post hoc comparisons showed a difference between the drugs at time 0 (p=0.03), a difference between the drugs at time 10 (p<0.0001) and a significant time effect for each drug (p<0.0001).For IgA (Clexane1=0.12±0.02, Clexane10=0.15±0.02, Cutenox1=0.12±0.03, Cutenox10=0.13±0.02) with significant effects for time (p<0.0001), drug (p=0.0078) and for the drug x time interaction (p<0.0001). The post hoc comparisons showed a significant drug effect at time 10 (p<0.0001). There was a significant time effect for Clexane (P<0.0001) but not for Cutenox. For IgM (Clexane1=0.11±0.01, Clexane10=0.13±0.02, Cutenox1=0.11±0.03, Cutenox10=0.13±0.02), there was only a time effect (p<0.0001). The post hoc comparisons showed no difference between drugs at either time, but significant time effects for each drug (p<0.0001). The immunogenic potential of LMWHs varies in terms of ability to generate A-HPF4-Ab, the antibody subtypes generated, and their cross-reactivity with pre-formed A-HPF4-Ab. Such parameters may be useful in defining the bioequivalence of generic LMWHs. Future studies evaluating the immunogenicity of different compounds in patients exposed to biosimilar drugs are warranted.


Disclosures: Jeske: PolyMedix, Inc.: Research Funding.