Replies to post #54649 on Biotech Values

[bladerunner1717]

Thomas,

I was wondering that myself. And does anyone know if the immunogenicity concerns of the FDA can be adequately addressed without having to conduct clinical trials? If Lovenox did have immunogenicity concerns, it could well be argued that MNTA's drug might have less immungenicity, due to less non-active ingredients--than the branded drug. But, of course, the FDA would want evidence of that and the question is again: Can the FDA's concerns over immunogenicity be alleviated by anything other than clinical trials?


Bladerunner

[DewDiligence]

The main AE to Lovenox is heparin-induced
thrombocytopenia (HIT). Here are some
excerpts from the Lovenox FDA label:

http://www.fda.gov/cder/foi/label/2007/022138,020164s075lbl.pdf

>>
5) WARNINGS AND PRECAUTIONS

5.5 Thrombocytopenia

Moderate thrombocytopenia (platelet counts between 100,000/mm3 and 50,000/mm3) occurred at a rate of 1.3% in patients given Lovenox, 1.2% in patients given heparin, and 0.7% in patients given placebo in clinical trials.

Platelet counts less than 50,000/mm3 [severe thrombocytopenia] occurred at a rate of 0.1% in patients given Lovenox, in 0.2% of patients given heparin, and 0.4% of patients given placebo in the same trials. [I.e. these events were higher in placebo, presumably a statistical fluke—Dew]

Thrombocytopenia of any degree should be monitored closely. If the platelet count falls below 100,000/mm3, Lovenox should be discontinued. Cases of heparin-induced thrombocytopenia with thrombosis have also been observed in clinical practice. Some of these cases were complicated by organ infarction, limb ischemia, or death.

6) ADVERSE REACTIONS

6.1 Clinical Trials Experience

In a clinical trial in patients with acute ST-segment elevation myocardial infarction, the only additional possibly related adverse reaction that occurred at a rate of at least 0.5% in the Lovenox group was thrombocytopenia (1.5%). [The word “additional” means incremental to the AE’s seen in the Lovenox trials in DVT secondary to elective surgery.]

6.2 Post-Marketing Experience

Local reactions at the injection site (e.g., skin necrosis, nodules, inflammation, oozing), systemic allergic reactions (e.g., pruritus, urticaria, anaphylactoid reactions), vesiculobullous rash, rare cases of hypersensitivity cutaneous vasculitis, purpura, thrombocytosis, and thrombocytopenia with thrombosis have been reported.
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