If you want to see just how balled up and distorted investor relations can get in biotech, look at AF's favorite whipping boy (for good reason) NWBO. You need to read the company's 12/10/13 press release saying the required events had been reached to trigger the 1st interim analysis for their GBM vaccine in ph 3. Then read their update on trial progress yesterday. Then read AF's analysis of the situation. Then the company's reply to AF. It's unfathomable. They claim no interim analysis has been done and yet they increased the power on their trial substantially, supposedly to control for an unforeseen variable.
Some background. Many companies build more into their interims than just a "continue or unblind" decision from the DSMB. Often there is an included futility analysis or an analysis to recommend increasing power by adding to enrolment. My guess is that is what has occurred. The DSMB looked at initial efficacy and recommended increasing power. I realize this is in direct conflict with management's claims, but it is just so much more plausible than their #$%$ and bull story.
"you appear to be correct there. can you give me a few others. just would help with my research"
Fast track drugs that failed. Insegia BLP 25 (tecemotide) Aidsvax G-Vax M-Vax Thermodox Oncophage BMS986094 Allovectin Tivozanib Bapineuzumab Darapladib Inaparib
Fast track is not a big deal. Most bigpharma do not issue a press release when a drug candidate receives the designation, FDA's Breakthrough designation is a big deal and is predictive of future success.
"On the flip side, doesn't it cost money they can't affort to lose to keep the trial going longer than needed?"
Not much. The vast majority and perhaps all of the participants have progressed and are off meds. That leaves the administrative side to collect event data, and that might be complete also. EXEL and the CRO could drag their feet for months on convening the DSMB and then reporting those results back to EXEL. Again, look at J&J and abi. Triggering event in January with a press release in October. FDA doesn't really care as long as everything is done in accordance with the protocol. This kind of information may eventually come out in ODAC and regulatory agency documents, but long after interest in the subject has waned.
"ernie, you are wrong - this is from SEC website:..."
Not this time. SEC has several rules governing material information. Insiders may not trade on the basis of undisclosed material information. Companies may not selectively release material information. And companies are required to promptly release several categories of material information. Four business days is the standard, not 72 hours. Form 8k lists the items requiring prompt release. Pivotal clinical trial results certainly meet the definition of "material," but do not fall into any of the specified categories requiring prompt release.
"If a public company doesn't release info pertinent to stock price, within 72 hours, the CEO can go to jail.."
Another message board myth. Absolutely untrue.
"A real possibility here is they are sitting on a negative trial result until COMET-1 passes to protect share price."
I think I was the first to raise that possibility, but I'm influenced by MMM's blanket assurance that they wouldn't do that. So, a bit reluctantly, my present thinking is that they just don't have the result in hand yet. However that doesn't preclude them somehow influencing a possible delay in the convening of the DSMB to complete the final analysis.
Give me time and I will give you dozens, The first that comes to mind is Biomira's Theratope.
"in thyroid there was a PFS benefit but no OS benefit... why wont the same thing happen here with Comet-1"
Good question. It certainly could happen again, but the EXAM (medullary thyroid cancer) trial should not be looked at as predictive for the following reasons.
The EXAM trial has undergone two interim analyses and the final analysis for survival is yet to come. The first analysis was designed to detect a PFS improvement at a statistically significant level if it existed. PFS compared to a survival endpoint is like comparing the result obtainable with a micrometer to a wooden yardstick. Differences are magnified and obtaining a statsig result is much easier. Because a PFS statsig result was an approvable endpoint, the EXAM trial was sized to obtain that result (330 patients). The larger a trial, the more apt it is to show an advantage if it exists. At it's last analysis, the EXAM trial demonstrated an advantage in median OS for the Cabo arm of 26 months vs 20 months. If that same advantage had been applied to a trial the size of the Comet 1 trial (960 patients), the end result would have reached statistical significance. The EXAM final analysis for survival is yet to come. I anticipate a further improvement in that 26mos vs 20mos, but we will have to wait to see if there is sufficient improvement to move the p value to a statsig result. So if one were to consider EXAM as predictive for Comet, then I would look for a positive result. However, these disease types are very different and the drug targets different oncogenic drivers in the two diseases so expecting the efficacy result of one to be predictive of the other is unreasonable. Safety and tolerability comparisons are useful and much of the MTC data was useful in the decision to lower the initial starting dose from 140mg/day all the way down to 60mg/day for Comet.
"...has gave the initial impression that biomarkers are all over the place."
That would be a generous interpretation because is the biomarkers are assumed to be reliable indicators of potential efficacy, then GRMD is a bust.
"......there has never – never – been a Fast Tracked drug that has failed to come to market?"
Absolutely, positively untrue. Fast track is not an endorsement of demonstrated efficacy. It is awarded on the basis of the "need" in the proposed indication.
"Is EXEL notified by the DSMB once the final analysis has been triggered; or is EXEL only informed upon receipt of results?"
I can speak to what's typical, but I don't even know which CRO EXEL is using let alone the specifics of the information that is passed back and forth.
It is normal for CRO's to pass along information regarding enrolment and event accumulation. In the past Gisela has made it clear that she is aware of where the trials stand in this regard but was unwilling to make any of that info public. What is not known is on which arm the events occur.
"...of a SELL THE NEWS reaction."
If I were looking for a short, I would look at the Ebola companies. I don't see an argument for a profitable business model. The disease can go into hibernation for years with few cases when it does crop up in populations with no money or insurance. The animal reservoirs are all in subSaharan Africa so there will never be more than traveler casude sporadic cases outside of Africa. Promises of government and DoD money (bioterror) will evaporate as soon as it falls off the front pages.
"Well, not exactly. Stock gapped up to $10.50 this morning only to lose it all. Longs over at MNKD board are absolutely dumbfounded now."
Hey, the same thing happened here when the FDA finally gave the thumbs up for MTC approval for MTC. There were estimates of a $100 million per year in revenue and the stock got chopped off at the knees when the reality sank in.
The thing to remember about the Comet 1 result is that it is very much a leading indicator for the follow on news in Comet 2, RCC and HCC. In CRPC, Cabo will not pull in a revenue stream comparable to Abi or MDV, it will be closer to the $400 million for Jevtana (Cabazitaxel). But there is room for growth above that in RCC and HCC and eventually other indications. So, a positive result in Comet should trigger a major shift in the valuation of the company. We'll see.
"This melanoma subject is being discussed on chat - Melanoma Research Foundation. Some interesting chats including this one:..."
This is one area that really shows that the technology is moving much faster than the regulatory process can accommodate it. Chronologically we have Ipi, Vemurafenib, Dab, Tram, Dab/Tram (all approved). Yet to come in the relatively near term are CoBrim, Nivo, Nivo/Ipi. On the horizon are TVec and various combinations of all the aforementioned drugs. This is one case in which everyone knows that that a combination approach is superior to the current SOC and it doesn't take much imagination to come up with one of those combinations. Also it is pretty clear intervention should start at the adjuvant stage, but again, this isn't SOC yet. If I had melanoma, I would seriously look for a clinical trial or look hard for an oncologist willing to go beyond the normal limits of recommended treatment. I suspect most patients are still getting Zelboraf (Braf + only), Ipi (if lucky), or Dab/Tram (again Braf+). I mentioned TVec. What an interesting drug that is (Amgen owned). It hasn't got much press yet, but it is low toxicity and shows efficacy regardless of genetic drivers and will lend itself to combination with other treatments.
"I was unaware of the early PET response, which at second glance appears singular to the Zelboraf/Cobimetinib combo."
I don't think there is anything published about how GSK's Dab/Tram combination fares using PET scan, so the "uniqueness" of this report may not relate to anything special or advantageous about the CoBrim combination. The perceived advantage attributed to CoBrim over Dab/Tram remains intact, but will receive renewed scrutiny when the CoBrim ph 3 data set is published. For the time being the advantage is based on an edge in reported OSS (88% vs 60something) and a slightly better safety profile.
I was looking at the Cougar 301 study which is the trial that resulted in approval of abiraterone in post-chemo CRPC. That trial reached its interim triggering event in January 2010. It reached statistical significance off that analysis, but J&J played it very close to the vest. The press release announcing the unblinding and successful topline result came out in Oct 2010. The final analysis triggering event actually occurred in September, before they even announced the interim result. They did not offer abi crossover to the control patients until October when the results were released. Bigpharma plays by different rules.
"If we assume 4-8 week data lock that puts us at late August/September for topline results under your 48 per month event rate."
I have no special insight into the DSMB's instructions, but I'm assuming that there was a delay for data cleaning before the March 24 announcement, so I'm guessing the actual interim trigger occurred in Jan/Feb. I would expect a similar delay period following the final analysis trigger. I really think the final analysis is underway as I type.
"I am going to tell you nicely that harassment is a violation of the ToS."
Are we talking video or slides? Who is the presenter? I just took a nap courtesy of Antoni Ribas but I don't think it was the right one.
"Ernie, after interim analysis didn't exelixis say they would have final results around yr. end?"
About a year ago, they were guiding first half 2014. That was changed to 2014, with no specifics as to when within 2014 or the order or the results (EXAM, Comets and CoBrim). By year end is not quite the same as around year end. No promises or guaranties, but this is going to happen soon.