Replies to post #54602 on Biotech Values

[stockdak]

MNTA: I think the FDA will require immunogenicity. I am guessing that MNTA product will be more like the pentasaccharide fondaparinux than LMWH in terms of HIT response. I could be wrong but it should be sorted out in a year.

Seems very similar to GTCB and the non-approval of ATRYN by the EMEA in Feb/Mar. In June there was a nice pop back when EMEA granted the approval upon -re-review. This is a big if for MNTA though.

1: Blood. 2005 Dec 1;106(12):3791-6. Epub 2005 Aug 18.

Anti-platelet factor 4/heparin antibodies in orthopedic surgery patients receiving antithrombotic prophylaxis with fondaparinux or enoxaparin.

Warkentin TE, Cook RJ, Marder VJ, Sheppard JA, Moore JC, Eriksson BI, Greinacher
A, Kelton JG.

Department of Pathology and Molecular Medicine, McMaster University, Hamilton,
ON, Canada. [e-mail]

Heparin-induced thrombocytopenia (HIT) is caused by platelet-activating IgG antibodies that recognize platelet factor 4 (PF4) bound to heparin. Immunogenicity of heparins differs in that unfractionated heparin (UFH) induces more anti-PF4/heparin antibodies than low-molecular-weight heparin (LMWH) and UFH also causes more HIT. Fondaparinux, a synthetic anticoagulant modeled after the antithrombin-binding pentasaccharide, is believed to be nonimmunogenic. We tested 2726 patients for anti-PF4/heparin antibodies after they were randomized to receive antithrombotic prophylaxis with fondaparinux or LMWH (enoxaparin)following hip or knee surgery. We also evaluated in vitro cross-reactivity of the IgG antibodies generated against PF4 in the presence of UFH, LMWH, danaparoid, or fondaparinux. We found that anti-PF4/heparin antibodies were generated at similar frequencies in patients treated with fondaparinux or enoxaparin. Although antibodies reacted equally well in vitro against PF4/UFH and PF4/LMWH, and sometimes weakly against PF4/danaparoid, none reacted against PF4/fondaparinux, including even those sera obtained from patients who formed antibodies during fondaparinux treatment. At high concentrations, however, fondaparinux inhibited binding of HIT antibodies to PF4/polysaccharide, indicating that PF4/fondaparinux interactions occur. No patient developed HIT. We conclude that despite similar immunogenicity of fondaparinux and LMWH, PF4/fondaparinux, but not PF4/LMWH, is recognized poorly by the antibodies generated, suggesting that the risk of HIT with fondaparinux likely is very low.

[DewDiligence]

Re: Other Lovenox ANDA’s

>Have other companies already tried to get their generic versions of Lovenox approved, but were shot down by the FDA?<

Amphastar and Teva submitted separate ANDA’s for Lovenox in 2003; neither has yet been approved. On MNTA’s CC three days ago, CEO Craig Wheeler stated that the FDA told him over the phone that these other ANDA’s will also be required to demonstrate non-immunogenicity.

Why haven’t investors heard anything about the generic-Lovenox ANDA’s from these companies?

For Teva, a change in status of this program does not meet the threshold of materiality for disclosure to investors and hence we won’t hear anything from Teva unless the news is positive.

Amphastar is a private company and it need not disclose anything. Amphastar’s partner is WPI, which had this to say about Lovenox on Tuesday: #msg-24335230.

I doubt that investors will hear anything more about the Amphastar ANDA unless the news is positive.