I'm actually happy that ASONEP came out first - if it had been the other way around, and ISONEP had been successful, we'd all be doubling down for the subsequent ASONEP trial, only to lose it all!
that's just flat out wrong. The phase 1 ASONEP results were vague and weak: "The study demonstrated that lymphocyte counts (the number of cells present in blood and lymphatic tissue) in the vascular space were reduced in a dose-related fashion," Phase 1 for ISONEP were much more convincing to me - it's what caused me to invest.
wildbill - sounds about right, right? I mean the guy is the regulatory affairs head, so there was probably some (hopefully inconsequential) screw up in communication with the FDA, or a filing getting botched or something. Given that there has been no announcement on subsequent trials, my guess is that he failed to get the necessary clearances from the FDA in a timely manner, which means they miss the "startup at the end of first quarter." So maybe there is a bureaucratic delay here for a couple of weeks...
well it was a joke. But, to get very serious with you MAC, this news is noise. 83K shares traded after hours versus 3.5 million during session. If any one of substance though this was a factor, this would have dropped $2-3 bucks. In any case, you should be encouraging me to joke about this - so far the announcement is working to your advantage.
opto, I sold half before the announcement, and I am all of that back again. The ISONEP trial is what interests me, not the ASONEP one. Do your own DD, but don't throw in the towel just yet!
Here's what happened on March 18th, in Dr. Shah's office:
"No, I swear Dr. Deshpande, I DID file the breakthrough therapy designation on 3102 at 6 weeks with Sovaldi, just as you had asked, and I had a copy of the application on my desk right here to prove it! I swear, it was right here..."
"Another potential benefit for the patients with occult disease was the resolution of RPE detachment, a potentially serious condition that is often a part of the pathology of wet AMD. Of the two occult patients diagnosed with RPE detachment in the Phase 1 trial, both experienced complete or near-complete resolution of the condition. Based on published studies, neither Lucentis nor Avastin produces this type of clinical benefit with a single dose.
iSONEP’s non-overlapping effects relative to anti-VEGF therapeutics was predicted prior to our clinical trial. As Campochiaro et al. state in Journal of Cellular Physiology 2009 Jan; 218(1):192-8, “Since S1P may have both independent and overlapping effects with VEGF, it is a particularly appealing target…”
agreed. Post hoc analysis may determine a benefit not readily apparent in the overall PFS number. Same thing happened in FOLD trials, But at the end of the day, I always considered Asonep just noise compared to the ISONEP trial in wet AMD, due late June. There were very encouraging signs from phase 1 in "heavily pretreated patients". Three of those patients showed a 12 letter improvement despite the heavy pre-treatments. Phase 2 has a good chance of showing a solid advantage. However, they have predominantly classic, minimally classic, and occult patients all mixed together in this trial, which I don't like, but the occult group accounts for 75% of the population with the disease. Here is from the phase 1 data: "Results from the iSONEP Phase I clinical trial were confirmatory in many respects. The most significant benefit observed was with the five patients diagnosed with some form of occult CNV (vs. classic CNV). Each of these five patients exhibited not only a positive biological response, but also a response that was independent of the effects seen with Lucentis and Avastin in wet-AMD patients.
Specifically, all of the occult patients with an active lesion (four of the five) exhibited a sizeable regression in their CNV lesion, with three of them exhibiting a reduction of greater than 75%. The CNV lesion is believed to be the underlying cause of the disease that eventually leads to degeneration of the macula, the area of the retina responsible for central vision. This type of clinical benefit is not typically seen with current treatments: published data suggest that, even with repeated Lucentis dosing, the total physical size of CNV lesion does not show much reduction, especially with a single dose (Heier JS et al. Ophthalmology. 2006;113:642e1-642.e4)."
Magnam awhile back you asked what company was "BLUE for the eyes" but I can't find the post now- it's AAVL. Their symbol stands for adeno-associated virus as that's the carrier for their fully functioning genetic splice that enables host cells to express a naturally occurring anti-VEGF protein, which inhibits new blood vessels and vascular leakage- hallmarks of wet AMD.
Macugen, your post is meaningless. First, Simeprevir is a macrocyclic protease inhibitor, not a microcyclic one, which to my knowledge doesn't exist. Second, sovaprevir is the PI Achillion will test with 3102/3422, and it is not a macrocyclic compound. ACH-2684 is. Third, there is zero evidence that a macrocyclic PI has any more of a drug-drug interaction with amiodarone than any other PI, or any more than a NS5A or NS5B does for that matter. Fourth, just like atazanavir,or Bristol-Myers' branded HIV drug Reyataz that can cause QT elongation OR arrhythmias, AND NOT SOVAPREVIR WHICH HAD BEEN INAPPROPRIATELY PLACED ON CLINICAL HOLD because of an AE that occurred when dosed in combination with atazanavir, amiodarone can also cause all sorts of cardiac exacerbations including worsening arrhythmias and QT elongation WITHOUT ANY PI OR OTHER DAA HEPC DRUG PRESENT. So, in other words, you are just throwing #$%$ out to see if it can stick on someone's fear wall. So post something informative and factual, instead of macrocyclic dung.
350,000 - 500,000 people die annually from hepc complications according to WHO. An infinitesimal number of people who have HepC are also treated with drug-of-last-resort options like amiodarone. And Barron's then reports that Harvoni's use may be limited? What a joke. The prize for best post goes to "catalano"on the GILD board who wrote: "Grapefruit sales will be down 50% on Monday." (NOTE: Grapefruit juice can increase amiodarone side effects by increasing the drug's concentration in the body).
FOLKS - THIS IS A NON-ISSUE. If GILD drops by a couple bucks tomorrow morning, I may buy it back again. For every dollar it drops, GILD loses $1.5 billion in market cap.
Thought I'd also quote "speedrunner" from the GILD board:
speedrunner199 • 7 hours ago Flag
"Bloomberg headline is completely misleading and out of context with reality
.Amiadarone is a rarely used anti-arrhythmic to treat more refractory arrhythmia (irregular hear rhythm) in patients unresponsive to other more commonly used medications. It has number of important and serious aide effect that limits its usage. Less than % 0.05 of Americans are on this medication.
Sovaldi when used with amiadarone is associated with bradycardia (slowing of the heart rate) in some patients and on patient has died from dradycardia. Thus, Gilead announced that sovaldi should not be used with amiadarone because of the potential risk.
Of the 250 K patients that are expected to be started on sovaldi this year, approximately up to 250 patients are expected to be on amiadarone- thus, 250 patients should not be treated with sovaldi or switched to a different anti-arrhythmic. The impact of restriction in amiodarone usage on sovaldi sales is negligible.
If you read the numerous toxicity associated with Viekra Pak and ribaviron, then you can have the appreciation of the huge safety advantage of sovaldi.
This headline by Blooberg is a sensationalism and completely misleads the readers."
This is why I (faosto) say that this is a non-issue - it's not a positive for ACHN, nor a negative for any of the treatments, including 3422/3102/sovaprevir. Bloomberg and other media are all on the prowl for sensational headlines in this sector - vastly increases their readership.
Thought I'd quote "young Doc" from the GILD board, who is a cardiologist:
Hold on. Please!!! I cannot believe the amount of garbage you people say. Amiodarone is great drug but it should not be used in anybody with liver disease including hepatitis C. I am a cardiologist. Second, amiodarone stays in your body for 6 months. So if you stop it today, it will be out of your system in september. This is a nonissue. Garbage news. Blame cardiologists who put these patients on amiodarone which by itself causes liver failure."
In Blue Cross Blue Shield Utilization Management Criteria for Abbvie's Viekira, there was already a warning about amiodarone (which is a highly toxic drug in just about every respect): Table 3: Potentially Significant Drug Interactions
Amiodarone, bepridil, disopyramide, flecainide, lidocaine (systemic), mexiletine,
Caution is warranted and therapeutic
concentration monitoring is
recommended for antiarrhythmics when coadministered with Viekira Pak.
It is unclear whether the interaction is with the NS5A or the NS5B or the PI.
This is sovaldi's revised warning as on 3/15 (and same for Harvoni):
Sovaldi prescribing info: WARNINGS AND PRECAUTIONS: Bradycardia with amiodarone coadministration: Serious symptomatic bradycardia may occur in patients taking amiodarone and SOVALDI in combination with another direct acting antiviral (DAA), particularly in patients also receiving beta blockers, or those with underlying cardiac comorbidities and/or advanced liver disease. Coadministration of amiodarone with SOVALDI in combination with another DAA is not recommended. In patients without alternative, viable treatment options, cardiac monitoring is recommended. (5.1, 6.2, 7.2)
I don't think this has any negative implications for Achillion, or for Gilead or Abbvie for that matter. "Amiodarone is intended for use only in patients with the indicated life-threatening arrhythmias because its use is accompanied by substantial toxicity." About 10-15% of HCV patients also have some form of cardiomyopathy. We are talking about a relatively small subset of patients, usually in a hospital setting, that are on these class III drugs for post myocardial infarction or life threatening arrthymias. This is more about the toxicity of amiodarone than the toxicity of HCV drugs.