PFE granted positive opinion by CHMP for Bosulif

http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2013/01/news_detail_001693.jsp&mid=WC0b01ac058004d5c1

Although they filed the first-line trial, it looks like CHMP is only recommending a second-line+ label. The language of the indication is somewhat strange (emphasis added): “Bosulif is indicated for the treatment of adult patients with CP, AP, BP Ph+ CML previously treated with one or more TKIs and for whom imatinib, nilotinib and dasatinib are not considered appropriate treatment options.”

My interpretation is that the bolded bit is a restriction of the second-line indication to patients who can't receive Gleevec, Sprycel or Tasigna instead of Bosulif. However, I could also see how it might be interpreted as an additional indication for a restricted first-line setting. Anyone have any thoughts?

I agree - I understand the analysts' concerns, and Ariad has been so transparent that there really aren't THAT many other things to ask about - but the volume of questions about the black box was a little overblown. FDA's approach and Ariad's explanation are both pretty simple and were sufficient to answer 99% of the analysts' questions.

I don't think Iclusig is TOO bad, but it sounds vaguely similar to "occlusive", which can't be a good thing for a drug with a black box about arterial thrombotic events!

The press release doesn't seem to specifically state whether it's a broad second-line approval, or if it's restricted by number or types of prior TKIs. Is the PI available yet? I haven't been able to find anything.

I can't think of any recent early rejections, either. My inclination is that there is no real incentive for the FDA to reject a drug early; if they do the extra work to get a drug APPROVED ahead of schedule, it makes sense because then patients will have access to it sooner. But I don't see why they would put the extra time and resources into making a rejection decision ahead of schedule.

Question for the biostats gurus re: alpha spend -

I'm trying to learn a bit more about biostats, trial design, the allocation of alpha to multiple endpoints, and how that affects subsequent thresholds of statistical significance. I suspect my question might have a very simple answer, but anyway.

Basically my question arises from the recent Abraxane melanoma data that was presented:

- Trial was designed with 80% power to detect a HR of 0.75 for PFS, with two-sided alpha of 0.049
- At the PFS analysis they did an interim OS analysis
- The confidence interval for the interim OS analysis was 99.9%

So my understanding is that this means for OS to have been significant at this analysis, p<0.001 ?

What about for the final OS analysis? Is the threshold still 0.001? Or does it change (i.e., do they get more alpha for the next analysis, so they just spend all 0.05 on OS)?

Apologies if these questions don't really make sense - I haven't been in a stats course since 10th grade!

RE: MRK anti-PD-1 MK-3475

The data is still very early, hard to compare with BMS' anti-PD-1 at this point - basically, both look great. Here is the MK-3475 Phase II:

http://clinicaltrials.gov/ct2/show/NCT01704287

Fairly huge randomized Phase II trial, granted with 3 arms. Could this be a registrational trial? Hard to tell the real SAP plan from CT.gov, but are ORR, PFS and OS co-co-primary endpoints? I'm no stats guru, but that would basically mean it has to hit higher hurdles for each endpoint, right? Although going vs. chemo, that probably won't be too hard...

Novartis has guided in recent calls that the base patent (I would presume the composition of matter patent, but I haven't really looked into it) for Gleevec expires in the US in late 2015. However, they also have a variety of patents on other isoforms/polymorphs/crstalline formulations that they will try to use to defend against generics beyond the base patent expiry. They have stated that they will provide a summary of these at the R&D day tomorrow, so maybe some more clarity there.

I am not sure where the 2019 date on the ARIAD call came from specifically, but Novartis has been suggesting that they will aggressively defend against generics beyond the 2015 patent expiry. How likely they are to achieve this is another question, that I do not feel at all qualified to answer!

http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm326654.htm

I hope this falls under the acceptable conditions for posting a link without any further context or insight :)

Seems like it will depend whether Lilly/the investigators can get everything ready by October 15th: http://www.ctad.fr/03-presenters/presenters.asp

Of course, I'm assuming it would be a presentation and not a poster; I can't find any details for poster deadlines on that website.

I don't think anyone outside the PPHM board wants to read through that much text on PPHM that ultimately reaches the conclusion that PPHM is the Microsoft of biotech. I mean, good God, man, get a hold of yourself.

I skimmed to the point of the Phase II second-line trial being characterized as an "FDA Gold standard" trial, then scrolled to the bottom. Apologies to others for engaging rather than ignoring the PPHMites.

I like this one: http://investorshub.advfn.com/boards/read_msg.aspx?message_id=79867811

The best part:

ONCY: Oncolytics Biotech Inc. Provides Update on Phase III Study of REOLYSIN® in Head and Neck Cancers

I am not invested in this company fiscally or mentally enough (i.e., not at all) to try to understand exactly what this update means, but I am curious to hear others' interpretation...

http://www.marketwatch.com/story/oncolytics-biotech-inc-provides-update-on-phase-iii-study-of-reolysin-in-head-and-neck-cancers-2012-09-12-718300

CALGARY, Sept. 12, 2012 /PRNewswire via COMTEX/ -- Oncolytics Biotech Inc. ("Oncolytics" or the "Company") CA:ONC -2.15% ONCY -0.35% today provided an update on its Phase III trial of REOLYSIN in combination with carboplatin and paclitaxel for the treatment of head and neck cancers (REO 018).

The Company has conducted an internal analysis of the blinded combined clinical data for all 80 patients enrolled in the first stage of the study. The study remains blinded at this time. At the time of the analysis, 23 patients of the 80 had not yet progressed but were included for the purposes of analysis. The median evolving progression free survival (PFS) of the 80 patients, which comprises the combined control and test groups, was greater than expected, as was the best response rate. On further examination, it was observed that patients for whom only metastatic disease was being measured by clinicians, were responding differently to treatment than patients who had local regional head and neck disease. Patients in whom only metastatic disease was measured had a median evolving PFS of 120 days, which was statistically significantly greater than those patients with a noted local regional head and neck tumor. There was a statistically significant difference in PFS between these two groups (n=80, p=0.008, hazard ratio=0.536). Oncolytics therefore believes that, based on differential PFS, it has identified two distinct patient groups are being enrolled in this clinical study, patients with local recurrent disease, with or without metastases, and those with distal metastases. Each of these two groups contains patients from both the control and test arms of the study. Oncolytics believes that these two groups of patients must therefore be considered to be different for the purpose of both analysis and investigation.

The Company has consulted with its principal investigators and the independent statistician for the study, and, on September 10, 2012, met with the U.S. Food and Drug Administration in Washington, D.C. Based on these discussions, the Company plans to expand enrollment in the first stage of the study to include 160 patients, all of whom have now been enrolled. Oncolytics intends to introduce an additional segregation to differentiate between patients with local recurrent disease, with or without metastases, and patients with distal metastases. Based on the analysis of the 160 patients, Oncolytics expects to generate randomized data from two discrete patient populations. The Company believes this will provide a sufficient number of patients to conduct a meaningful analysis of the two identified patient groups, as well as increased powering for the overall analysis. Oncolytics intends to treat this expanded first stage of the REO 018 clinical trial as a separate supportive study to a planned registration study that will be similar to, and take the place of, the original second stage of the REO 018 clinical trial. Enrollment in the first stage of the study is complete and no additional patients will be enrolled pending approval of a planned registration study. The Company intends to submit protocol amendments to regulators in the immediate near term to reflect these changes. It will require additional time to follow the expanded group of patients and allow the evolving PFS data to mature.

"Segregating and separately evaluating the two identified patient groups means we will be able to obtain our first randomized data in these two patient populations, including one with only metastatic disease," said Dr. Brad Thompson, President and CEO of Oncolytics. "All six of our randomized Phase II studies are examining indications with significant metastatic disease involvement. Patients with metastatic disease represent a large potential market."

Conference Call Details

Dr. Brad Thompson, President and CEO of Oncolytics, will host a conference call and webcast on Wednesday, September 12th, 2012 at 6:00 a.m. MT (8:00 a.m. ET) to discuss in more depth the Company's Phase III study in head and neck cancers. To access the conference call by telephone, dial 1-647-427-7450 or 1-888-231-8191. A live audio webcast will also be available at the following link: http://www.newswire.ca/en/webcast/detail/1034181/1121577 or through the Company's website at www.oncolyticsbiotech.com/presentations . Please connect at least 10 minutes prior to the webcast to ensure adequate time for any software download that may be needed. A replay of the webcast will be available at www.oncolyticsbiotech.com and will also be available by telephone through September 19th, 2012. To access the telephone replay, dial 1-416-849-0833 or 1-855-859-2056 and enter reservation number 30393545 followed by the number sign. The Company also intends to post the prepared remarks from the call to its corporate website following the call.

Agreed. She may not explicitly rule out AA, but it is abundantly clear from her analysis that if she were asked 'Can bavituximab get AA based on this trial?' her answer would be 'no'.

Agreed re: wanting to see the baseline characteristics, but just want to note that DTIC is dacarbazine, whereas the PPHM trial used docetaxel as the comparator.

FDA approves PFE’s bosutinib for 2nd/3rd-line CML:

Agree, terrible name. Makes me think of encephalitis or something. I am curious to see how 'Bosulif' does; I would expect it being saved as a salvage therapy because of the GI tox and lack of long-term data, but it will be interesting to see how it goes against Sprycel and Tasigna in the 2L+ setting and what kind of share (if any) it can get. Remember that unlike ponatinib, 'Bosulif' does not have 1L approval on the horizon, as its head-to-head against imatinib (Phase III BELA trial) actually failed to meet its primary endpoint back in 2010.

FDA approves enzalutamide (MDV3100) for CRPC

http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm317838.htm

So, it's called 'Xtandi'. Not sure how I feel about that...

Need help with biotech story...

This probably doesn't qualify, as it's not really biotech, it's relatively old and well known at this point, and there has already been plenty of ink spilled over it. Nonetheless, it's such a great story that I can't help suggesting it: Brian Druker discovering imatinib for CML. Basically turned a deadly cancer into a chronic disease overnight.

If you're interested in the story, there is a good interview with the NYT:
http://www.nytimes.com/2009/11/03/science/03conv.html?pagewanted=all

And even if this is too obvious for the purposes of your book, I would recommend to ALL who are interested in pharma and biotech to look into the story; it really is amazing.

perifosine at ASCO...

What about LBAs of negative trials that haven't had top-line releases stating that they are negative? Perifosine and bapi were both announced as negative before being presented. Don't get me wrong, I am not at all trying to insinuate that no news is good news re: PPHM and am frankly confused why the PPHMers are still being engaged as if they can be reasoned with at all, but in my limited experience, I can't think of a LBA that has been negative without having some sort of top-line release ahead.

I suppose it is probably different for company-sponsored vs. co-op group trials as well, but all the negative LBAs I can think of have been known to be negative before. Again, just want to reiterate that I am in no way suggesting this has any bearing on PPHM, but it did make me a little curious.

Just get a little irritated when someone suggests that Dr Gerber's plenary presentation could be about failure

Why? As stated before, failed trials are featured in major sessions all the time (e.g., perifosine)

General question about PDUFA dates scheduled on weekend.

If a PDUFA date is scheduled on a Saturday, will the FDA actually take approval action on the weekend? Or is there any trend of Saturday PDUFA dates being acted on on the preceding Friday or the following Monday?

Maybe I'm being cynical, but it seems unusual for a PDUFA to be scheduled for a weekend - we're talking about government employees, after all! :)

But can they coformulate a mAb and aptamer? I don't think I've ever heard of a mAb coformulation and my instincts tell me that it wouldn't nearly as "easy" as it might be with small molecules/orals.

Phase IIIs with HR for OS < PFS

Yervoy too: http://www.asco.org/ascov2/Meetings/Abstracts?&vmview=abst_detail_view&confID=102&abstractID=80592

Makes sense that this might be a more common phenomenon with immunotherapies.