Just hope my conviction that this can be fixed isn't misplaced. Always like to have counterarguments backed with referenced facts. Based on what we know, Ampion is competitive with current therapy. It's what we don't know that I worry about.
Do you know of a specific example of a BLA submission with 1 small (N lt 500) Phase III and a Phase II not involving life-threatening (eg, cancer) or orphan diseases (low numbers inherent)?
Rolling *might* be possible, but it has to achieve Fast Track in order to do that.
I haven't been following the specifics of FLXN, so would not want to guess. It is some time prior to results though, so it might be no different than AMPE 2-4 months before STRIDE results. A triple in AMPE may be possible with (a) encouraging comments from the FDA (b) especially with running BLA (c) partnership or, even better, buyout. But, all highly speculative at this point.
As I mentioned previously, it might be possible with a rolling BLA. But, before we get too excited, recall Ampio's pre-BLA FDA guidance: "Two adequate and well-controlled trials with reproducible evidence of efficacy are required to support approval of a novel product for…the management of the pain of OA…[T]here is one primary endpoint, either a pain score such as the NRS or the WOMAC pain subscale"
– FDA Pre-IND Meeting Minutes
There is 1 adequate and well-controlled trial: SPRING. STRIDE was adequate, but not "well-controlled". It therefore fails to meet the FDA requirements.
This is a sustained release of TCA, which is the current standard of care. Phase IIa was successful, but they didn't release results only claiming "the pain relief experienced by patients was “amongst the largest ever seen in clinical trials.” Amongst is a key word.
The advantage of sustained release corticosteroid by IA is reduced systemic effects and longer duration of action. FX006 is now in Phase III vs Saline with estimated 24 wk endpoint Dec 2015.
If a few senior managers spent a few million dollars of their own money buying their stock in the open market, it might support the confidence they claimed during the cc.
If that timeline is reasonable, they don't have enough money to wait for BLA approval, assuming (against the odds) that the next trial is a success. They either dilute or have to partner. Any potential partner knows that and will adjust price accordingly. Of course, raising cash with a submitted BLA is a manageable task too.
exactly - as the OP stated - not the type of publicity we were looking for. Reading MM's statement post-STEP regarding the FDA possibly accepting the results is comical (were it not so pathetic)
I doubt anyone can predict *accurately* what the FDA will decide. A new trial is certainly likely, probably necessary and anticipated by management. If the FDA acknowledges efficacy was found in the Ampion arm relative to baseline, that could be a positive development. We don't know the effect size in KL4. If it is larger than that previously noted, another positive. I have a more optimistic view of the timeline than others:
Release of final 24 wk results by May 15
FDA guidance early/mid-June (coincident with new trial start)
STRUT end: Nov/Dec (most likely without MRI analysis)
End of next Phase III trial: Feb/Mar, 2016
It's more than retail investors. There were a substantial number of shares held by institutions.
And, yes, one of the articles referred to Bausch & Lomb (Valeant) experiencing similar freezing problems. So it is not just an Ampio issue.
And yes, industry does learn from the mistakes of others.
would if I could,but this is/was already a big investment. There are still many unknowns. I'm holding, but don't pretend to advise others.
Indeed. It has also allowed previously "hidden" posters to offer good comments and has eliminated (or at least seriously reduced) the cheer-leading faction so much that I now appear among the most optimistic on the board!
dovsafir - I looked exclusion requirements for STRIDE again. You would have been excluded from that trial, therefore it is likely you will be excluded from the next.
The STEP disaster is becoming an example for the industry of how not to ship sensitive material.
Not the type of publicity that's wanted, but query the following:
Temperature-controlled Logistics Address Cold-Chain Challenges
Planning essential to ensure temperature control, say logistic firms
A few apropos comments from a recent article. I hope MM doesn't continue harping on a flawed AAOS study. It makes a poor impression on physicians who know better.
From PhysiciansWeekly, 2014
Over the years, the few studies that have assessed the use of intra-articular HA injections in patients with knee OA often exclude subjects with end-stage knee OA. “This makes it challenging to assess the true safety and efficacy of these products,” says Dr. Myerson. “We need more evidence on use of intra-articular HA injections in appropriately selected patients. These treatments are often given to patients at a time when OA has progressed beyond mild or moderate. Intraarticular HA injections will not benefit patients once their knee OA becomes severe. Healthcare providers should be offering this treatment option to patients earlier in the disease course.”
Standardized Mean Difference(SMD) vs Saline
Timeframe Avg SMD 95% CI
4 to 13 weeks 0.43 0.26 to 0.60
14 to 26 weeks 0.38 0.21 to 0.55
(Conventional interpretation of SMD: 0.2 small, 0.5 medium, 0.8 large. Generally speaking, 0.5 is MCID, but this is vs an active placebo).
“The most recent AAOS recommendation regarding the use of HA in knee OA is based on a number of clinical trials with poor diagnostic inclusion criteria,” says Dr. Dasa. “The data that were used to reach a consensus recommendation on HA injections were based on patients with significant variation in OA severity and included products that were not FDA approved. We have studies that demonstrate the usefulness and effectiveness of HA injections in patients with mild or moderate knee OA. These benefits, however, diminish as OA progresses to
advanced disease. The AAOS guideline fails to distinguish which patients can benefit from HA injections.
an exceptionally expensive experiment prior to getting approval for pain. Bad strategic move given limited resources. There are already better options, including stem cells and TPX-100 in trial. SC is proven, but still needs to be made consistent (as well as affordable, even if 1-time therapy). Also look at Agili-C.
This story is only about pain relief better than HA's. If it can't do that, it's toast.
Maybe not even that. They first have to file a case. This is usual BS about trying to put a case together. Almost all don't go forward.
"investigating potential securities claims" contains 2 keywords: "investigating" and "potential".
Agree about regeneration data - that is an exceptionally long wait: ca. 6 months. What Bar Or referred to was just ex vivo data - petri dish, as it were. Interesting, but meaningless without in vivo data. If they had animal data, that would add a lot of strength. But, they decided to test the concept in clinic. The inflammation process cannot be adequately modeled ex vivo. Particularly since it takes months to see in vivo effect. Then, if it's not quality hyaline cartilage, the benefit is marginal.
A control does not get a p-value. The p-value is a measurement of how significant the differences are between the 2 arms (for simplicity sake - it's actually a measurement of whether the null hypothesis can be safely ruled out at a particular level, generally 95% or greater).
The saline control was expected to have an average effect (ca. 35%) with +/- deviations symmetrically distributed on both sides of the mean. It does not, therefore clearly something not due to random error happened. So, it cannot be concluded that Ampion exerted an effect better than saline (and probably not even for a significant portion of the sites - it must have been several sites with issues).
However, the p-value of 0.001 for Ampion reduction in pain relative to the baseline means the drug has an effect. They really should have emphasized "clinically relevant" (ie, larger than is normally seen for saline) in the PR. But....