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Can you post the link ?
AVNR - if we were to go strictly by SPA guidelnes for Primary End-points for both efficacy and safety, they should get the approval. But this is all in theory
Piano, the more you wish good luck, more the stock tanks .... please don't wish us luck
Exactly..that's what I thought when I saw the Motley Fool note. Wonder where these guys come from ? !
AVNR vs BIOD mix-up
For all your reasonings, why then FDA accepted the data as part of the filings. I believe BIOD had discussed this outlier with FDA as part of the filing.
Hey, I posted enough messages on this board to qualify as an Executive, no ? This is without counting ton of pm's and taking phone calls from Johny Who....and double that for being both long and short at the same time
Your blog has nothing new other than simply quoting the article. The Gekkowire is flatly negative while the other link focuses on AMLN debacle comparison.
You are almost convincing that FDA could reject AVNR's zenvia due to their undisclosed shelf offering...LOL...
AVNR - Insider roster has Craig Wheeler...interesting he being CEO of MNTA...may be he can bring his good luck to AVNR come October 30th.
Torpedo the spa ? The whole SPA protocol is to collaborate with FDA on a trial that will not leave any doubt on agreed end-points (both on efficacy and saftey). On both these accounts, AVNR STAR trail met its primary end points goal.
With regard to mortality rate...
Per AVNR VP..
...Benevich: There were 2 separate assessments done for deaths reported in the STAR trial. Consistent with Good Clinical Practices, investigators were asked to assess the study-medication-relationship for adverse events using the following explanations: Not Related, Unlikely, Possible, Probable, Highly Probable. There were 7 deaths reported in the STAR trial, all among patients with underlying amyotrophic lateral sclerosis (ALS): 3 in the AVP-923 (30/10) group, 3 in the AVP-923 (20/10) group, and 1 in the placebo group. Six of these were reported by the investigators as not related, while the seventh was reported by the investigator as ‘possibly’ related to study medication.
Following standard procedures, detailed clinical narratives were created for each case. This information was reviewed by an independent mortality adjudication committee on a blinded basis. All deaths were classified by the committee as respiratory related and likely due to the progression of the underlying ALS. No acute decompensation of respiratory function after initiation of study drug was observed, and no deaths were ascribed to a cardiac cause.
ALS is a relentlessly disabling neurologic disease that inevitably progresses to respiratory failure and death. When respiratory muscles weaken, a cascade of events leading to respiratory failure can be observed. Death usually occurs secondary to respiratory failure or respiratory complications and the average life expectancy of an ALS patient is about 2-5 years from time of diagnosis. All data related to the 7 reported deaths were provided to the FDA as part of the full response filing.
One more reason to say that Safety is not an issue with AVNR..
What Bydureon CRL Means for Avanir Pharmaceuticals
By Rockford Coscia, on October 20th, 2010
Yesterday, Amylin (AMLN), Alkermes (ALKS), and Eli Lilly (LLY) announced receipt of a complete response letter (CRL) for Bydureon – a once-weekly treatment of Byetta (exenatide), a currently approved once-daily treatment for diabetes. As approval was widely expected for the second go around for Bydureon (A CRL was issued in March of this year), Amylin’s share price plummeted after its rejection – dropping over 50% to start the day. Alkermes’ share value was also down as much as 25%.
As all of the above companies are well above the $1 billion market cap that I provide as somewhat of a coverage limit, I devoted very little attention to the above FDA decision. Additionally, there wasn’t much news to speak of – approval was widely expected. Very, very few, outside from apparently this guy, thought this wasn’t an extremely likely approval. The decision, however, does impact a stock that is of especially high interest to the readership here at BIP, Avanir Pharmaceuticals (AVNR).
That’s because the Bydureon CRL was based largely on the fact that the FDA was concerned about prolongation of QT interval – a measure of electrical rhythm within the heart – a concern that was also expressed by the FDA in Avanir’s first CRL for AVP-923. The concern is serious, as QT interval prolongation can be associated sudden cardiac death. Likely due to this association, Avanir’s stock price is down today as well – over 4% as of this writing. Many have interpreted the event as the FDA playing hardball with fluctuations in QT interval.
But is the argument that a CRL issued on QT interval should cause a decline in Avanir’s share price valid?
I’d first like to address what the FDA has stated with regards to QT prolongation. In its Guidance for Industry report on the Clinical Evaluation of QT/QTc Interval Prolongation, the FDA states that threshold level for regulatory concern is around 5 ms prolongation. The reason for the wording ‘around 5 msec’ is because the agency would like to see the upper bound of the 95% confidence interval of QTc prolongation to be below a 10 msec prolongation threshold.
Schematic representation of normal ECG trace, from Wikipedia
Quinidine, one of the ingredients in Avanir’s AVP-923, is an antiarrythmic agent. One of its main therapeutic purposes, then, is to change problematic electrical currents within the heart. It is also a good inhibitor of cytochrome P450 2D6, an enzyme important for the metabolism of a number of exogenous drug molecules. It is this second action that AVP-923 exploits to allow dextromethorphan – a drug metabolized by the cytochrome P450 2D6 pathway – enough time in the body to demonstrate a clinical reduction in psuedobublar affect (PBA) episodes.
It was due to quinidine’s first therapeutic action, QT interval prolongation, that Avanir received its initial CRL (then called an ‘approvable letter’) in 2006. In the trials submitted in AVP-923’s first NDA, the quinidine pushed the mean QT interval prolongation above the 5 msec threshold. After discussions with the FDA, the company decided to reduce the amount of quinidine in the drug from 30 mg to 10 mg. Avanir would then have to run an additional trial under a special protocol assessment (SPA) that would demonstrate safety and efficacy, as well as demonstrate that QT prolongation was under the thresholds set out in the FDA guidelines. A summary of those results are available here.
Now there are several ways in which to calculate QT prolongation; the two most standard being the Bazett and Fridericia corrections. The reason for this is that the interval must be adjusted to the changes in patient heart rates. According to Avanir, the highest therapeutic dose in the new studies (30 mg dextromethorphan/ 10 mg quinidine) showed mean interval prolongation of 3.0 and 4.8 msec, depending on the correction method used. In the lower therapeutic dose (20 mg dextromethorphan/ 10 mg quinidine) the reported mean prolongation are either -1.9 or 1.0 msec. In either of the dosage levels, the QT prolongation falls within the levels set forth in the FDA guidelines.
The bottom line, then, is that the Bydureon CRL should mean nothing in regards to AVP-923’s approvability. Avanir conducted its STAR trial under an SPA agreement and AVP-923’s QT mean prolongation fell within the guidelines published by the FDA. PDUFA dates always carry risk – regardless of the market’s certainty of approval as evidenced by the current Amylin debacle –but the QT issue should not be a contributing factor Avanir’s risk on October 30.
But Lovenox did not have a generic at the time of this PR...?
Yes. It was a good observation on your part and I am not sure why it got deleted either..
We will get approved. One more tangential reference as towhy....AVNR did the right thing..took the SPA route and not a shortcut like AMLN did....see below (part of the article posted)
The Short-Seller Who Got Amylin Right
Adam Feuerstein
10/20/10 - 10:15 AM EDT
NEW YORK (TheStreet) -- Not all investors are shocked and upset about the decision by U.S. regulators to reject Amylin Pharmaceuticals'(AMLN) diabetes drug Bydureon. Short-sellers -- investors who bet that Amylin shares would fall -- are positively giddy and making money.
Amylin shares are down $10.35, or 50%, to $10.14 in Wednesday trading.
How did the shorts get Amylin right when a majority of investors believed Bydureon was going to be approved? I spoke with one Amylin short early Wednesday about his bear thesis. This hedge fund manager asked to remain anonymous because the rules of his fund forbid him to speak publicly about his investments.
"I always believed that Amylin and Eli Lilly(LLY) were taking shortcuts to get Bydureon through the FDA" and the agency was going to have problems with this approach, said this short seller.
Some bozo dropped a 100 shares at the low print. Also someone bought at 3:15 and that's where we are hanging at this point...
Fortunately I am picking up more
Big relef QTc data. Not an issue for AVNR unlike AMLN...so more cocnfident that AVNR will get approved.
pcrutch, in light of the interview which obviously has removed lot of misgivings, what's your approval percentage, if I may ask ? TIA
P.S Please keep up the good work.
Third world will eat FDA's lunch if they continue to reject such as this. Companies such as AMLN should partner overseas for markets abroad as risk mitigation strategy
From $heff's board...he is no idiot
AVNR ($3.14)...solid article that pcrutch had with key management of AVNR. He cut right to the chase and asked the questions that investors & shareholders needed answered. That is more than a lot of the conjecture I hear on the board. People know who the source is and know of the intention as a shareholder. Very well done! I look forward to next week when we hear of a decision! $heff
Awesome job..after seeing the interview report, bought 10k more at 3.15...i think AVNR crossing 4+ prior to PDUFA date.
This should be positive, right ? Almost an extra year on the 30/10 arem for the mean time when the death was reported got to be good.
biomedreports article ? If anthing significant is posted, I seriously doubt anyone in AVNR would have shared such information two weeks before PDUFA data. I would expect the poster to quote AVNR source if the article is to be treated with any merits.
Cancord has come out earlier that they had extensive talks with experts especially on latest safety details. No concerns whatsoever. The Gekko guy has hidden several facts based on the comments posted on his website...see for yourself...
I am holding my 20k shares all the way to approval.
What's really frustrating is this 'overhang' on MNTA PPS due to potentially TEVA getting the approval (if at all).
IMHO, other than Oppenheimer no one is buying the analyst take at this point.
5K at 14.75. Any loss now will be on the top of previous level at 20+ and again at 18+ buys..
Made a stupid mistake of buying based on cancord note. Somthing ugly is brewing on for sure..
Doji or hammer..whatever...I actually see couple of nails being driven down the head of shorts...lol
As $Sheff pointed out, Gekkowire's omissions on factual information related safety raises intention befaind their article so close to the PDUFA date.
IMHO, likely these guys shorted at high's and plan to cover low using these scare tactics...
Saftey Profile based on P3 trials..no alarming issues...the gekkowire article is overblown..
Safety Evaluations
Side effects were recorded throughout the clinical trial period. The
administration of AZ-004 was generally safe and well tolerated. The most
common side effects reported (> 10% in any treatment group) were taste
(dysgeusia), dizziness, sedation and headache. These side effects were
generally mild to moderate in severity, and occurred in both drug and placebo
dose groups.
Treatment Emergent Side Effects
(> 2% in any treatment group)
Placebo 5 mg AZ-004 10 mg AZ-004
Term (n=115) (n=116) (n=113)
Dysgeusia 3 % 9 % 11 %
Dizziness 10 % 5 % 11 %
Sedation 10 % 13 % 11 %
Oral
Hypoaesthesia 0 % 1 % 4 %
Headache 14 % 3 % 3 %
Somnolence 3 % 3 % 3 %
Nausea 5 % 1 % 2 %
Vomiting 3 % 1 % 1 %
Agitation 3 % 1 % 0 %
There were two serious adverse events reported during the trial: exacerbation of schizophrenia (1 patient in the placebo group) and gastroenteritis (1 patient in the 10 mg group). Both of these events were scored by the investigator as "unrelated" to study drug.
FWIW I am holding all my shares thru PDUFA date.
Picked 3k more at 3:04 AH..good opportunity, IMHO
Everyone should just relax. The filing today is the registration of stock that was part of the Hercules loan deal. See SEC filing Schedule D dated 5/12/2010. This has been public information for months and is nothing to get all worked up about. They were granted the right to 376,394 shares as part of the loan arrangement, and now want to be able to sell their stock, which they could not do unless it was registered. That is all the filing today is about. This is not a bad thing. If AZ-004 gets it approval, Hercules wants to cash in on the rise in stock price, just like everyone else. The sky is not falling.
Management is not selling any stock, they cannot until after 90 days after the last dilution, it is in the SEC filings. So everyone take a deep breadth, put away the charts and relax.
You seem to get delighted by your postings every time AVNR tanks..sounds like you are a short. If you don't like its trading, then you must like something about AVNR to still keep posting your messages !!!!
Why is MNTA dropping like a rock ? It has become just another sink-hole biotech lately
Glad I held on to my shares and not sell hoping to buy back cheap. AVNR may never look back now...
fwiw, Ayer Capital Management that I track closely have bought QCOR as of 8/16. This fund does great DD on upcoming breakout biotechs.
I am very positive QCOR will get approved in September.