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Isis Pharmaceuticals, Inc. Message Board

  • caveat_emtor caveat_emtor Oct 20, 2005 4:58 PM Flag

    ISIS301012:Effective for 60 days? How?

    I have a question on the effectiveness of ISIS-301012. It appears that a loading dose of 3 to 4 injections of about 200 mg followed by a weekly injection for three additional weeks can maintain LDL lowering of about 30% for two additional months. This type long effect lowering of LDL. It could be obtained in addition to the use of a statin such as Zocor that goes generic middle 2006. While all this looks very good, as things have looked for Isis in the past, it can all fall apart just like all the other anti-sense drugs Isis has tested. The real question is why if ISIS 301012 different in that its effect lasts for 2 additional months. Here are some points to consider :

    1. The half life of ISIS 301012 is many months in humans ? Looks unlikely but can explain the finding.

    2. The drug enters hepatocytes that make Apo B100/assemble VLDL, the drug remains within the cells for months and causes anti-sense destruction of Apo B message. ISIS 301012 is different from past anti-sense drugs that found it difficult to enter cells.

    3. The small Phase 1 trial supporting this data was a fluke or had faulty reporting (it was not done in the US, possibly in Eastern Europe).

    Considering that ISIS 301012 may act in addition to statin treatment makes it an attractive drug for partnering. A recent example of such a drug is Zetia that was combined with Zocor to give Vytorin. Such a combination can help towards the LDL target that is being lowered downwards over the years.

    The biggest statin player is Pfizer, then we have Merck, Astra Zeneca, Bristol Myers and Novartis. A partner may come from these or even other big pharma that do not have statins as they can do combination with generic statins.

    Serious competition for ISIS 301012 comes from microsomal transfer protein (MTP) inhibitors. These reduce Apo B, LDL and TG far better than ISIS 301012 and are oral drugs to be taken daily. Some of the players listed are expected to have such drugs in testing and could make comparisons readily.

    Can anyone explain how ISIS 301012 works ? What bugs me most is "its effect lasts for 2 additional months".

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    • Jet, I didn't mean it that way.
      I was giving Dark and his minions grief about the "Old School Articles" A Day old, week old and so on.. Info from 5 yrs ago is ....well anyway.

      It's good to see you're a Sports Fan.. Yes "Go Blue"

      Their QB is a really good athlete

    • Dan, I assure you his mind is not dinosaur like. Blu might go undefeated this year except for this week. Go Blu starting on 10/10/10. t

    • Since I like "Kickin It" Old School. I dug this up via google.

      Maybe the new name of "dogsdazed"
      is "DinosaurDazed" because info from 5 yrs ago is quite a long time!

      Anyway maybe you will enjoy LOL

      Google Expert =P

    • Very interesting post, as usual.

      Don't waste your time with Caveat (Vae victis!).

      This New Isis young fox is starting to run up, jumping on $ 6,00 hedge.

    • There are a couple of issues to bear in mind:

      First: If I am not mistaken, Pravachol comes off patent protection in April 2006 and Zocor loses its protection 2 months later. Lipitor maintains protection until 2010.

      Second: Pfizer will probably come out with a combination product consisting of Lipitor and torcetrapid to prolong some degree of Lipitor patent protection.

      Third: Generic forms of Pravachol and Zocor will place a great deal of lower price pressure on the entire statin market and will almost certainly and dramatically errode Lipitor dominance (both as a single or combination agent).

      Fourth: The new medicare prescription drug benefit plans and growing presence of private health insurance drug benefits will add a great deal of additional pressure to move from branded statins and branded statin combinations to generics.

      The losers will not only include BMS (Pravachol)and Merck (Zocor), but also Pfizer. Merck will be a double loser since it also has a share of Vytorin (simvastatin combined with ezetimibe) -- these agents will be less expensive if prescribed individually.

      The winners will be new compounds which can be prescribed individually with a generic statin. This would include Zetia and potentially Isis-301012. I have read that Pfizer will not offer torcetrapid as a single agent.

      Zetia combined with low-dose statin results in about a 52% reduction in LDL; with moderate-dose statin, 58%; and with high-dose statin, about 64%. As pointed out in an excellent recent New England Journal of Medicine article, side-effects increase significantly as higher doses of statin are used.

      Lipid management guidelines have progressively become more stringent. With LDL-C targets of 70mg/dl or less for high risk patients, statin alone (or even combined with Zetia)may not be sufficient. As these patients with coronary artery disease or coronary artery disease equivalence have to meet lower and lower LDL-C levels, Isis 301012 could be an important agent.

      There are also a significant number of statin intolerant patients. Therefore, Isis-301012 may potentially have a large market when combined with a statin or when used as a single agent. With the upcoming phase II trials, we will have a much better idea about 301012's promise and potential problems. Thus far, it has looked very promising.

    • My take from having simavastatin in the combo : BMY (pravastatin), AZN (rosuvastatin), PFE (atorvastatin), NVS (fluvastatin) are out of the race for partnering.

      MRK has already dropped-out of the partneship on PTP 1B, with generic simavastatin, it makes little sense to partner for ISIS-301012 (one drug is injectable, other is oral, cannot have a single pill to extend franchise).

      This means Isis is looking for a non-statin (one that does not market a branded statin) partner for ISIS-301012.

    • I looked at the books. This boat is sinking fast.

    • You got a real swinger here. Down down and down. Chapter 11 dead ahead!

    • I thought you might like to know.

    • babsy knew that. she didn't want her son to know.

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