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Isis Pharmaceuticals, Inc. Message Board

jetmanbash 260 posts  |  Last Activity: Apr 15, 2014 8:52 AM Member since: Dec 29, 2004
  • Reply to

    Another verification of the AKT target in CA:

    by jetmanbash Mar 22, 2014 11:35 AM
    jetmanbash jetmanbash Mar 23, 2014 2:24 PM Flag

    Hey KG! Good to hear from you. Guess G is knocking off some steelheads with P. stay in touch. t

  • Reply to

    Okay I see the pattern forming now

    by ballsacklover Mar 22, 2014 4:25 PM
    jetmanbash jetmanbash Mar 23, 2014 1:58 AM Flag

    You don't know shxt about shxt. The stock has held strong relatively speaking. The message is getting out about what the pipeline has to offer. Whenever the stock drops there will be plenty of buyers at whatever lower price there is to pick them up on the cheap based on the pipeline and true potential. All of that baby talk that is R or X rated won't cut it and you will be shown as the puzzy you really are. t

  • 5-epi-Torrubiellutin C shows antiproliferative activity on DU145 prostate cancer cells through inactivation of the AKT/mTOR pathway
    Anti-Cancer Drugs, 03/20/2014 Clinical Article

    Singh A, et al. – The current study aimed to determine the anticancer potential of Torrubiellutins by defining the molecular mechanism of cytotoxicity using DU145 cells. The results showed that the inhibition of prostate cancer cell growth by 3a was associated with inhibition of anchorage–independent growth, cell migration, and, to a small extent, apoptosis–mediated cell death by caspase activation.

  • Reply to

    New target for AEGR from LS:

    by jetmanbash Mar 20, 2014 3:01 PM
    jetmanbash jetmanbash Mar 21, 2014 10:02 AM Flag

    Yep, it is a sure thing. You should go out and buy a place in the Carribean right now. t

  • Aegerion Pharma (AEGR -0.71%) Target lowered to $66 from $86 at Leerink Swann

  • Reply to

    Part III:

    by jetmanbash Mar 20, 2014 2:34 PM
    jetmanbash jetmanbash Mar 20, 2014 2:37 PM Flag

    Part V:

    Wait and see
    If everything continues to work in evolocumab's favor there's a strong chance that Amgen could file for a new drug application before the end of 2014. There's also a decent shot, since it would be for an orphan (or rare) disease, that the FDA could expedite the review process, possibly bringing a third FDA-approved drug to select HoFH patients before mid-2015.

    More importantly, improved quality of life may await HoFH patients.

  • Reply to

    Part III:

    by jetmanbash Mar 20, 2014 2:34 PM
    jetmanbash jetmanbash Mar 20, 2014 2:36 PM Flag

    Part IV:

    Furthermore, in ongoing testing being done on evolocumab, the side effects have been incredibly mild relative to the boxed warnings of liver toxicity forJuxtapid and Kynamro. The TESLA trial noted that adverse events were balanced across treatment groups, with the most common being upper respiratory tract infections, influenza, gastroenteritis, and nasopharyngitis. In other words, evolocumab could possess a considerably better safety profile which may warrant preferential treatment from physicians if a patient is determined by genetic testing to be responsive to evolocumab.

    Finally, as Herper pointed out in his discussion of evolocumab, because it targets high cholesterol, in general, through multiple trials and studies that will include around 30,000 people, if approved it'll have a huge market of potential patients. What that means for the consumer is a significantly lower annual price than Juxtapid or Kynamro, which are strictly geared toward a few select indications.

    Wait and see
    If everything continues to work in evolocumab's favor there's a strong chance that Amgen could file for a new drug application before the end of 2014. There's also a decent shot, since it would be for an orphan (or rare) disease, that the FDA could expedite the review process, possibly bringing a third FDA-approved drug to select HoFH patients before mid-2015.

  • jetmanbash by jetmanbash Mar 20, 2014 2:34 PM Flag

    Amgen's new therapy is unique in that it targets a protein known as PCSK9 which binds with LDL receptors and allows high levels of LDL cholesterol to persist in HoFH patients. However, a natural mutation of PCSK9 can actually cause a dramatic reduction in cholesterol in a patient which lowers the risk for cardiovascular disease. Amgen's evolocumab works by mimicking this mutation and inhibits PCSK9 from binding with LDL receptors, leaving more of those receptors free to remove LDL cholesterol from an HoFH patient's blood.

    Earlier this week, Amgen released its latest findings in its TESLA phase 2/3 trial on evolocumab for HoFH. The first part of its phase 3 study met its primary endpoint of a clinically meaningful and statistically significant reduction in LDL cholesterol from baseline at week 12. Although specific data wasn't released, Amgen said it plans to release that information at an upcoming medical conference and through subsequent publications. Overall, Amgen's phase 3 program for evolocumab involves a whopping 14 separate trials that will evaluate its long-term safety and efficacy among a number of cholesterol-based diseases, including HoFH.

    What's really intriguing about Amgen's therapy is that it's a subcutaneous injection given just once monthly for 12 weeks, then followed up with one injection every two weeks for another 12 weeks. Add that up and you're looking at just nine injections over 24 weeks, compared to 24 injections for Kynamro and 168 capsules for Juxtapid over the same time span.

  • jetmanbash jetmanbash Mar 20, 2014 2:25 PM Flag

    Part II:

    Aegerion's Juxtapid has been the early standout despite an annual treatment price tag that is more than $119,000 higher than Kynamro. Juxtapid is a once-daily capsule taken in the evening well after a last meal; it works in conjunction with proper diet and exercise to remove LDL cholesterol from a patient's blood. While it did reduce LDL cholesterol levels by approximately half during the first 26 weeks of study in its phase 3 trial, it also comes with a boxed warning regarding liver toxicity: Juxtapid can cause the accumulation of fat in the liver, as well as liver enzyme abnormalities. The FDA's approval was given on the condition that Aegerion run three post-marketing studies regarding the safety of long-term use of the drug.

    Sanofi and Isis' Kynamro is an injection given to patients once a week that also works as an adjuvant therapy to proper diet and exercise to lower LDL cholesterol. Cholesterol levels for those taking the drug fell by a tamer 25% during the first 26 weeks. It, too, comes with a boxed warning due to the potential for liver toxicities associated with accumulation of fat in the liver and liver enzyme abnormalities. The drug-company duo was also required to run four post-marketing studies mainly to establish the long-term safety of the therapy.

    Meanwhile, select HoFH sufferers may soon have a new therapy to lean on if Amgen's (NASDAQ: AMGN ) phase 3 studies continue to deliver primary endpoint-meeting results.

    A wonder drug in the making?
    The experimental therapy, which Forbes' health care columnist Matthew Herper said could become a direct competitor for about one-third of Juxtapid users, is evolocumab, known also as AMG 145.

  • Theobromine, the primary methylxanthine found in theobroma cacao, prevents malignant glioblastoma proliferation by negatively regulating phosphodiesterase-4, extracellular signal-regulated kinase, akt/mammalian target of rapamycin kinase, and nuclear factor-kappa b
    Nutrition and Cancer, 03/17/2014 Clinical Article

    Sugimoto N, et al. – The purpose of this study was to determine whether theobromine could exert growth inhibitory effects on U87–MG, a cell line derived from human malignant glioma. Theobromine, a caffeine derivative, is the primary methylxanthine produced by Theobroma cacao. The authors show that theobromine treatment elevates intracellular cAMP levels and increases the activity of p38 mitogen–activated protein kinase and c–Jun N–terminal kinase, whereas it attenuates p44/42 extracellular signal–regulated kinase activity and the Akt/mammalian target of rapamycin kinase and nuclear factor–kappa B signal pathways.

  • Reply to

    Looks like a bottom is forming...

    by stan91724 Mar 17, 2014 3:46 PM
    jetmanbash jetmanbash Mar 17, 2014 7:48 PM Flag

    Please tell me what it says??

    Aegerion Pharma: Hearing Deutsche Bank defending AEGR following AMGN data (51.71 -0.80)

  • Reply to

    You are an idiot if???

    by stan91724 Mar 14, 2014 1:52 PM
    jetmanbash jetmanbash Mar 17, 2014 10:40 AM Flag

    You seem like an angry person, hope you're feeling better. t

  • Reply to

    ZAP2 is here, look for ZAP3 sometime soon:

    by jetmanbash Mar 17, 2014 9:27 AM
    jetmanbash jetmanbash Mar 17, 2014 10:08 AM Flag

    Potential competitors within 12 to 18 mos could be: AMGN, REGN, MDCO, SNY, and maybe even PFE and their partner if they get their PCSK9 inhibitor underway. t

  • Reply to

    ZAP2 is here, look for ZAP3 sometime soon:

    by jetmanbash Mar 17, 2014 9:27 AM
    jetmanbash jetmanbash Mar 17, 2014 9:39 AM Flag

    If the price for the AMGN product is about $20 to $40K there is a chance that many insurances will have patients show that they fail this product first, then they can get the honor of paying $350K for a twenty year old drug. t

  • Reply to

    ZAP2 is here, look for ZAP3 sometime soon:

    by jetmanbash Mar 17, 2014 9:27 AM
    jetmanbash jetmanbash Mar 17, 2014 9:38 AM Flag

    If the stock can go UP ten points in minutes from bad news for potential competitor, what should it do when that competitor becomes real with good news?? t

  • Amgen announces positive top-line results from Phase 3 TESLA trial of evolocumab (AMG 145) in patients with homozygous familial hypercholesterolemia; study meets primary endpoint of LDL cholesterol reduction (122.54)

    Co announced that the Phase 3 TESLA (Trial Evaluating PCSK9 Antibody in Subjects with LDL Receptor Abnormalities) trial evaluating evolocumab met its primary endpoint of the percent reduction from baseline at week 12 in low-density lipoprotein cholesterol (LDL-C). The percent reduction in LDL-C, or "bad" cholesterol, was clinically meaningful and statistically significant. Evolocumab is an investigational fully human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9), a protein that reduces the liver's ability to remove LDL-C from the blood.
    Safety was generally balanced across treatment groups. The most common adverse events in the evolocumab group (more than one subject) were upper respiratory tract infection, influenza, gastroenteritis and nasopharyngitis.
    Details of the Phase 3 TESLA trial will be submitted to a future medical conference and for publication.

  • jetmanbash by jetmanbash Mar 14, 2014 12:41 PM Flag

    Low volume and stock not moving down much. The CEO knows the potential of these drugs already. He will under promise and over deliver. t

  • Activation of the PI3K/AKT pathway correlates with prognosis in stage II colon cancer
    British Journal of Cancer, 03/13/2014  Clinical Article
    Malinowsky K, et al. – Patients with UICC/AJCC stage II colon cancer have a high 5–year overall survival rate after surgery. Nevertheless, a significant subgroup of patients develops tumour recurrence. Currently, there are no clinically established biomarkers available to identify this patient group. The authors applied reverse–phase protein arrays (RPPA) for phosphatidylinositide–3–kinase pathway activation mapping to stratify patients according to their risk of tumour recurrence after surgery. This data indicate that activation of the PI3K/AKT pathway evidenced on the protein level might be a valuable prognostic marker to stratify patients for their risk of tumour recurrence. Beside adjuvant chemotherapy targeting of upregulated PI3K/AKT signalling may be an attractive strategy for treatment of high–risk patients.


    Full–length proteins were extracted from formalin–fixed, paraffin–embedded tissue samples of 118 patients who underwent curative resection.
    RPPA technology was used to analyse expression and/or phosphorylation levels of six major factors of the phosphatidylinositide–3–kinase pathway.
    Oncogenic mutations of KRAS and BRAF, and DNA microsatellite status, currently discussed as prognostic markers, were analysed in parallel.

    Expression of phospho–AKT (HR=3.52; P=0.032), S6RP (HR=6.3; P=0.044), and phospho–4E–BP1 (HR=4.12; P=0.011) were prognostic factors for disease–free survival.
    None of the molecular genetic alterations were significantly associated with prognosis.

  • This company has it together. They have excellent people in charge, they have carefully constructed their plan and mission. The biomarker AKt1 may be the most important in all of CA and they are approaching it by using an ANS drug to go after it because the target is probably undruggable with small molecules, or even Mab's. Keep the faith, and have a three year time horizon and you will be richly rewarded. t

  • jetmanbash jetmanbash Mar 12, 2014 9:39 AM Flag

    Archie, to flip it around the other way.....your presence here could be considered the kiss of death for this stock. Remember the last time, when your neighbor told you there was nothing wrong with LIPD and to buy more?? Uh-oh...t

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