Watching "City Confidential" in the background. The AVNR commercial has run a few times. The voice over says things like "brain injury" and "dementia". Since when did those get on the label? Been months since I've looked at AVNR, so it's a fact based question.
Right now, the company is testing for MS pain, and you have emphasized the importance of this market in terms of AVNR's value. One of the arms of the MS pain study is 45-10. The structure of the trials was done with full FDA involvement. Why would the FDA approve Phase II trials of MS patients if they were afraid of administering too much Dex? I think another arm was 30-10.
I agree that the QT prolongation did not lessen, but I believe the FDA was concerned in that regard with the Quinidine component, not Dex.
Sarge, what Ray conveniently leaves out is the fact that the drug approval process takes into account the pressumed overall health issues the targeted population is forced to endure. People with ALS and MS have a compromised system to begin with and are likely to be dramatically more fragile than a population of folks with primarily pain issues. In fact, Ray himself made that distinction not that long ago while waxing on about why he owns the stock.
"Why would the FDA approve Phase II trials of MS patients if they were afraid of administering too much Dex? I think another arm was 30-10."
Sarge, it is wrong to assume that if a company decides to study a certain dosage of a drug, that the FDA is likely to approve that dose.
Regardless of how much input the FDA has in a study, and even if the FDA suggests studying a higher dose to a company, that does not mean the FDA has no concerns about the safety of the higher dose or that the FDA is likely to approve the higher dose.
Obviously, this is true just from our experience with Avanir. The STAR study had an SPA (Special Protocol Assessment). So there was a lot of input from the FDA in the STAR study and the doses studied were 20 dex/10 quin and 30 dex/10 quin.
The FDA did not approve 30 dex/10 quin. for PBA
I'm sure there are some PBA patients who are not adequately controlled with 20 dex/10 quin who might do better with 30 dex/10 quin. If dex/quin were benign from a safety perspective, the FDA would have approved 30 dex/10 quin.
Here's the important point:
One thing the FDA is always interested in is the, "minimal effective dose".
In dex/quin's case, by giving the Approvable response in October, 2006, the FDA insisted on searching further for the minimal effective dose (probably initially mostly because of the quinidine, but clearly dex was an issue in the final analysis also).
And once the minimal effective dose was established, the FDA declined to approve the modest dose of 30 mg of dex.
The answer to your question as to why Avanir is studying 45 dex/10 quin and 30 dex/10 quin is simply because, from the study data that we've seen, 20 dex/10 quin probably does not work for neuropathic pain.
30 dex/10 quin may not work either, although I'm hopeful it does, since it seemed to have some effectiveness in the subset of MS patients with neuropathic pain in the STAR trial.
Since 30 dex/10 quin may not work, or may not work for everyone, they have to study a higher dose, like 45 dex/10 quin. which I am confident will show statistically significant efficacy for pain.
On the one hand, pain is a more compelling medical issue than PBA, so the FDA may be more willing to approve a dose higher than the minimum effective dose of 30 dex/10 quin (if that dose gets statistically significant results for efficacy in PRIME and the two Phase 3 studies that will come after PRIME). So the FDA might approve not only 30 dex/10 quin but also the higher dose of 45 dex/10 quin.
because the benefits of treating pain effectively, outweigh the increased risk of the increased dex.
But in PBA's case, obviously the FDA thought that the risk of the increased dex outweighed the benefit of treating some people's PBA more effectively with the increased dex.
The FDA approved Nuedexta for PBA for all conditions, no matter the source. So whether the reason for the patient's PBA is MS, ALS, TBI, stroke, Alzheimer's, or whatever, it's ok for the company to advertise to or educate potential patients.
Now, if the ad were to mention pain, speech and swallowing, irritability, or anything else that's currently just being tested, the company would be overstepping its bounds.
I agree with your statements and certainly AVNR can market N for PBA due to any underlying condition causing it. However, I don't think the ad even directly markets N. I've only seen one ad but from what's been described AVNR only mentions/describes PBA, that there is a treatment, and to "ask your doctor".
This is a common strategy because if company mentions a drug by name then they also have to describe just about every possible side effect and warning which can be overwhelming and counterproductive.