Thanks for the correction. I got my information from the clinicaltrials website. Apparently NKTR doesn't supply all the information about the trial to them.
It appears to be the document excerpt that makes Yahoo (jerks) barf. Go to page 16 of the document. Read the paragraph that starts "Seeking an...".
Search for "FDA Guidance for Industry Non-Inferiority Clinical Trials". It's all about the margins. Document also discusses the complications of using an active comparator instead of placebo.
BEACON is structured as a superiority trial. OS is the sole primary endpoint. There are no secondary endpoints.
Survival prolonged in Avastin naïve patients when combined with Avastin in Phase 2 study. There was a trend towards improved OS (but not significant) in Avastin refractory patients. Avastin improves PFS but not OS in GBM. It looks like CLDX will discuss AA with the FDA pending a Phase 3. The rindopepimut Phase 2 was much larger than the NKTR-102 GBM Phase 2.
This may open another path forward for NKTR-102.
I have information to post about FDA guidance for non-inferiority trials and NKTR-102 BEACON if Yahoo (jerks) will let me. There is much more risk than we might have believed.
The PBYI study compared neratinib plus paclitaxel against Herceptin plus paclitaxel (which is the current standard of care).
You missed the point of the post. Like NKTR-102 im BEACON, neratinib was compared to the current standard of care. Neratinib matched the standard of care in efficacy. The PBYI PR promoted the study as showing superiority in reducing CNS metastases. The issue is that it takes a much larger sample group to show non-inferiority. 700+ patients as on BEACON probably won't be enough with as similar results.
Neratinib failed primary endpoint superiority, but greatly improved at preventing CNS metastases. Very closely matched standard of care. Doesn't seem to matter, market appears to view it as a failure.
I've also been trying to bone up on non-inferiority studies. BEACON is powered to show superiority, but not sure it is sufficiently powered to show non-inferiority unless NKTR-102 just barely misses at superiority. There is a lot online from the FDA about what constitutes an approvable non-inferiority study, not all of it is settled.
It's getting whupped on high volume. Any particular reason, or is this a trading opp?
I agree, guru. Investors usually go the other way, buying out of the money puts to protect them in case of disaster. People who are levered on the wrong side of a biotech failure are the ones whose brokers hit them with market sells at the open on the following day.
There's an old joke, a guy arguing with a gay rights activist.
Guy says, "Why stop with gay marriage? Let's introduce polygamy, it's been accepted in societies around the world. Not just a man with multiple wives, why not for example, three men and two women? And why should a person be limited to one marriage at a time, why can't you be married to several consenting people at once? Some people love their animals, why can't a person be married to their pet?"
Gay rights activist replies, "Now you're getting ridiculous!"
Guy says, "Yeah, but you started it."
Also, here is an important quote from the article...
"Oxigene might try to demonstrate the fosbretabulin+Avastin is safer or better tolerated by patients than Avastin+chemo, but that's also a tough task."
That would be a path for approval for NKTR-102 in the BEACON trial if superiority isn't conclusively demonstrated. I think this is the scenario that is priced into the stock currently. Even so, NKTR-102 would require a trend towards improved OS and HR for this to be a go.
I've heard of data locked by an independent data monitoring board. This is the first time I have ever heard of data locked by a company after it was received. Every time a company gets data, the data is unlocked to see what it is.
I'd say this is an April Fool's joke, ha ha, but today is November 12. Does anyone out there realize how ridiculous this is?
Negative cash flow goes from about $13M to $17M last quarter. Expenses to increase dramatically with new hiring. I expect another dilution before the end of 2015. Hopefully it will be from a much higher stock price.
Highlights the issues faced by OXGN and its drug fosbretabulin. The article indirectly shows the waste of money that the NKTR-102 OC studies were.
Search for "Oxigene Faces Challenges for Ovarian Cancer Drug Even With Encouraging Data".
Scanned the eribulin studies at the clinicaltrials website, saw a couple of differences compared to the NKTR-102 Phase 3. Not sure how they will play out.
The eribulin studies were open to patients at ECOG level 2. The BEACON study is for patients ECOG 0 or 1 only.
A factor that may have contributed to improved OS in the eribulin Phase 3 is that the number of previous treatments was essentially unlimited in the Phase 2 studies. It was limited to five in the EMBRACE study, as it is with BEACON. At least one patient had 27(!) previous treatments in the Cortes Phase 2 study.
Here's some additional color to hijack's concerns. We discussed this back at the time of the Phase 2 MBC completion, time to dust off the old analysis. The median OS of 13.1 months for the 21 day cycle was based on 35 patients. The OS of the 14 day cycle (also 35 patients) was 8.8 months. That's a monster difference. If you look closely at the Kaplan-Meier graph, you will see a large survival difference between the 16th and 17th patients in the 21 day cohort. Shift the curve one patient to the left and median OS becomes about 10.3 months. A single patient survival is probably the determining factor in running this $100M+ Phase 3!
And to apca, the marker analysis could be of use in subsequent studies, but not this one. It's purpose is to identify patient entry criteria for future studies who might respond best to NKTR-102. Strong correlation to success when one or more markers is present would not salvage the BEACON study if it fails. It's called data mining. Also, see the work of FMI and others working on genetic analyses of cancers. One of the objectives is to try to identify the drug(s) that would be most effective against a person's specific cancer. There is a movement towards treating cancer by genetic type rather than by body location.