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I don't know.
I asked a related question on the BV board. This is the response from a former Genentech employee:
http://investorshub.advfn.com/boards/read_msg.aspx?message_id=79985310
dependent on the contract, but most likely the CRO will have to pay some penalty but not be financially responsible for a full trial. You wouldn't want that same CRO doing the next trial anyway.
This is hard to blame on a CRO as the sponsor should have oversight. Every trial I have worked on as a separate unblinded person (in the company or consultant) who doublechecks the vendors's(CRO) treatment assignments.
Randomization and treatment assignment mishaps are the most important aspect to control and have good oversight on because they can completely ruin a trial. You can be hands off in other areas if you are low on resources, but not in this area.
http://investorshub.advfn.com/boards/read_msg.aspx?message_id=79879413
You either have an unblinded statistician in house or another unblinded consultant to oversee or just double check. This is a given in every trial I have worked on and the lack of shows pphm's inexperience
Agreed.
UPDATED
I sold out on Monday.
I have been responding to PMs and have sent a few PMs myself to try to sort through this mess.
I hope FTM is right, that the only arms affected are the two treatment arms. It seems possible to me. Whether or not that will be enough to allow us to partner, I don't know. I believe the trial is now broken as far as the FDA is concerned.
Ultimately we won't know until we know. But there's too much risk, now, for me to hold through.
GLTAL
I never short development stage biotechs. They have enough problems without contributing to their inability to fund their research. Why would I screw a company that may, someday, save my life?
Isn't Dart's cost basis per share around 1.34? I wouldn't make a lot of assumptions about the support here. A lot could be happening.
Possibility 1: There are various algos for accumulation and distribution.
Possibility 2: The first day after a collapse always finds support from those who cannot believe the s*** really hit the fan.
Possibility 3: Somebody knows that BP is signing a deal with PPHM even as we tank.
Possibility 4: This is a nightmare and I will soon wake up in a cold sweat.
Possibility 5: The mistakes were in the treatment arms and a partnership is still possible. Somebody already knows this...
We're going to have to be patient and wait for clarification. It sucks, but that's where we are.
Each to their own risk tolerance...
Makes one wonder about that chart on Friday. Looked like a classic Max Pain day, stock tanking into the end of the day. Then out of the blue, some white knights appeared and drove the price back up ... and over 11,000 contracts ended the day in the money.
First thing monday morning, boom. Those 1+ million shares were down 4+ million dollars.
Big sell offs almost always have a dead cat bounce. Catching a falling knife is dangerous. This is bigger than a knife.
Hope the dosing to individual patients was consistent throughout the trial. That would be the best possible situation.
Not hopeful.
How long until we hear? I'm thinking 2-3 months to sort it all out.
My guess, they knew there was a problem already by the time the held the cc on Sept. 10th.
http://investorshub.advfn.com/boards/read_msg.aspx?message_id=79406600
Their lack of confidence may have been, in fact, their realisation that they had a very serious problem.
I replied to FTM. Best case, IMO, is that all affected patients are censored.
IMVHO
The reason I think it's a problem is that Dendreon had a clerical error on their PIII. The initial p-value reported on the trial was .8 ish and after the clerical error was fixed, the p-value dropped to .52 ish. The FDA never accepted the lower p-value and evaluated the trial based on the higher number.
I saw another trial where there was a mixup, every patient affected by the screwup was censored.
Crossing my fingers, but I'm pretty pessimistic.
I cannot see how that will be possible. From the FDA's perspective, the protocol is bust. The prospective design was violated. The results will be invalidated.
IMVHO
Good point.
Maybe, but the press release states,
As part of the trial's execution, Peregrine contracted with independent third-party contractors to execute treatment group assignments and oversee clinical trial material coding and distribution according to established procedures.
That, to me, sounds like they are talking all three arms.
(earlier response to a PM)
I think it looks bad.
They report great 1st line data and 3 months later, BAM! and they say it's a difference between their reads and the independent investigator reads.
They report great 2nd line data and now, BAM! and they say it's the fault of a 3rd party.
This is after stating in conference calls that they expected the government contract to be renewed and BAM! it wasn't.
They are serial share/price killers.
I'm willing to withhold judgement. But I am not at all optimistic. I would expect, at the least, that the trial endpoints were all invalidated. MOS may be in question.
I doubt they will be able to recoup their losses through insurance.
They have that 30 million dollar loan now. How are they going to pay that off?
Dilution will be catastrophic.
They're screwed financially. They are blood in the water to Wall Street sharks.
I think their only hope is to sell the company, cheap.
I may change my mind after I hear what they have to say, but I can't yet imagine how the situation could be any better than this.
Who is going to trust the PII pancreatic data now?
And if the ISTs don't report some good data...?!
I had a really bad feeling after the last conference call. I covered my cost basis but I should have been smarter and taken some profit.
Biotech, you never know. And, honestly, there was smoke. You have to manage your risk.
I'm not going to take PPHM's word that the screw up was all 3rd party. I hope it was but they've been on a downhill roll since the government contract was cancelled.
One would think a fully responsible third party would be on the hook for the entire cost of the screw up. But we don't know if they even have the ability to pay. Was it an American company? Were they insured? To what degree? I hope we can recoup our trial cost losses and some. But even that may not help us. And compensation could be years away...
So much unknown. Ugh.
There are still people living much longer than expected. I'm not convinced it's a placebo. We may never have the chance to find out.
I'm wondering if the problem occurred across geographies or if this is a problem with the foreign sites only...
Unmitigated disaster.
If, as appears likely, the trial results are compromised (it is a prospectively designed trial in which the prospective protocol wasn't followed, invalidating the results) it will be a two and a half year setback.
The PIII meeting with the FDA is in jeopardy if not completely blown out of the water.
All partnership discussions are suspended until they sort out the impact on the data but, best guess, all partners will wait to see reliable data - unless they can partner for a song.
The loan looms large and, if this goes as bad as seems likely, dilution will be catastrophic to current shareholders.
Hoping for the best but the best doesn't look to be anything less than awful.
IMHO
They had this discussion on the Elan board a few years back. At the time the law was, if the company has not said that it is open to a buyout or merger, they do not have to disclose any offers. They are not for sale. End of story. Until they change their mind.
I think what you're witnessing is Max Pain on OpEx. It doesn't have to close at 5 dollars or below. The sellers made premium when they sold the options.
Helpful. Thanks.
I thought the rumour of pancreatic data on Friday was provocative.
The trial enrolled over a year and a half - FTM's consideration noted. Typical OS is around 7.2 months.
Enrolment ended in June, but given the time to enrol and that the study completion date is December 2012...
The fact that it's open label ... I wonder how many people have seen the data.
Data on Friday is not out of the question, IMVHO.
Yes.
TUSTIN, CA -- (MARKET WIRE) -- 01/05/11 -- Peregrine Pharmaceuticals, Inc. (NASDAQ: PPHM), a clinical-stage biopharmaceutical company developing first-in-class monoclonal antibodies for the treatment of cancer and viral infections, today announced that it has initiated a randomized Phase II clinical trial in patients with previously untreated stage IV pancreatic cancer.
TUSTIN, CA -- (Marketwire) -- 06/25/12 -- Peregrine Pharmaceuticals, Inc. (NASDAQ: PPHM) today announced the completion of enrollment and randomization of 70 patients in a Phase II trial evaluating bavituximab in combination with gemcitabine versus gemcitabine alone in patients with previously untreated stage IV pancreatic cancer.
All I can say is, it's a bet I'd be very happy to lose. Friday will be interesting if they show encouraging data from the pancreatic cancer trial. It's a full P2 with 70 patients enrolled.
This is prospective, randomized, open-label, multicenter, phase 2 study of gemcitabine with or without bavituximab in patients with previously untreated stage IV pancreatic cancer.
Estimated Enrollment: 70
Study Start Date: January 2011
Estimated Study Completion Date: December 2012
Estimated Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Primary Outcome Measures:
Overall survival of patients with stage IV pancreatic cancer treated with gemcitabine alone or gemcitabine with bavituximab.
15 enrolment centres in the USA
4 enrolment centres in the Ukraine
Investopedia on volume and open interest
http://www.investopedia.com/articles/optioninvestor/04/060904.asp
Do you believe in Max Pain? I'd bet a beer those 12,209 September $5 calls all expire out of the money. It's a dirty game.
Caveat Emptor.
CP, Don't forget the rat experiment Thorpe related in the NYAS presentation. Rats with a genetic modification that would constantly produce new prostate cancer cells were treated with Bavi. After the planned treatment cycle, Bavi cleared the system and the rats lived on to ripe old ages ... for rats. How could that be?
The immune system learns when bavi unmasks a tumour. The learning isn't unlearned when Bavi clears the body.
Hence, when the rats were cut open after they died of old age, Thorpe discovered the genetic modification caused the body to continuously produce new prostate cancer cells, but the rats' immune systems always recognised the new instances of the cancer and successfully kept the new cancers at bay.
How much of the PS has to be masked to allow the body to learn that a cancer is hiding? I'd guess not all of it. In theory, it would seem, the animal has to live long enough for the immune system to be educated and turn the tide against the cancer.
I see a lot of us leaning on Garnick's statement re: "Having personally been involved in the evaluation of over 30 Phase II trials over my career, none of which ever achieved statistical significance, including many of today's blockbuster biotech products" A word of caution:
http://investorshub.advfn.com/boards/read_msg.aspx?message_id=79417508&txt2find=garnick
What people? Oh, I probably put the "person" on ignore already... ;o)
clinicaltrials.gov
I believe the two most successful completed trials were the NSCLC and Advanced and Metastatic Breast Cancer trials.
http://clinicaltrials.gov/ct2/results?term=bavituximab+completed
The most successful had been run outside the USA - India, Russian Federation, Georgia, Ukraine.
When I called Peregrine and asked about their quality control measures three-four years ago they said they monitored the foreign sites at least monthly according to the international standards I mentioned in my last post.
The ongoing trials (most are ISTs) are largely located in the United States.
Pancreatic has 15 USA sites, 4 Ukraine sites.
Rectal Adenocarcinoma is all USA
Castration Resistant Prostate Cancer is all USA
Her2-Neg Metastatic Breast Cancer is All USA
Liver Cancer is all USA
NSCLC with Pemetrexed is all USA
Two of these trials are expected to report out data by the end of the year.
The current PIIb trials in NSCLC are both split about 50/50 USA and exUS.
The earlier Indian trial was run using RECIST.
http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=74&abstractID=48393
The trial was monitored according to International Conference on Harmonization (ICH) and Good Clinical Practices (GCP) guidelines.
http://www.fiercebiotech.com/press-releases/peregrine-pharmaceuticals-reports-positive-results-phase-ii-bavituximab-lung-cancer-0
The trial that most closely tracks the docetaxel/bavituximab trial protocol that's at the centre of the current controversy was done in Advanced and Metastatic Breast Cancer. That data was very impressive as reported at ASCO:
http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=74&abstractID=43470
Background: Bavituximab, a novel IgG1 monoclonal antibody which targets membrane phosphatidylserine complexed with ß2-glycoprotein I on tumor vasculature was tested in combination with docetaxel in a multicenter open label phase 2 trial in adults (n=46) with locally advanced or metastatic breast cancer.
Methods: Subjects received intravenous administration of weekly doses of 3 mg/kg bavituximab on days 1, 8, and 15 of a 28-day cycle for up to 6 cycles along with docetaxel 35 mg/m2 in a Simon 2-stage design. Tumor response was determined by use of the Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
Results: 46 caucasian female subjects median age 49 (range 30-72) were treated. Prior treatment included chemotherapy in all 46 pts (100%), surgery in 40 pts (87%), and radiation therapy in 13 pts (28%). Overall response rate (CR+PR) was seen in 28/46 (60.9%, CI 45.4-74.9) with clinical complete response seen in 10.9% and partial response seen in 50%; median progression-free survival (PFS) of 7.4 mos (95% CI, 6.0-9.0); median duration of response (MDR) of 6.0 mos (95% CI 5.6-7.0).
FWIW - My sense after following the company carefully for the last nearly four years: they went to India and Georgia because they were broke. I don't get the sense they went there to cheat. They did what they could to ensure the trials were well run.
Iwfal and ex,
bavi showed 43% ORR in an open-label, INDIAN NSCLC trial. In the ongoing, MULTICENTERED (inc. USA), open-label PIIb for 1st line NSCLC, the investigator reads recorded 25% ORR.
When it's said that Asians live longer, does that include India and would you think the drop in ORR was related to the shift to a mixed, as opposed to a oure Asian population in the two trials? In other words, would a shift of 18% be in the ballpark of the expected shift moving from pure Asian to a truly mixed population in such small trials?
Understood that we are looking at n=49 in the Indian, open-label trial and that the ability to assess may not permit strong conclusions given the limitations of the trials.
I similarly asked CJ to reinstate iwfal's post earlier this morning.
Iwfal's one of the best biostatistics people you will find on any message board. He may have a point of view, but don't confuse that with his integrity regarding the rigours of biostatistics. In this area, as far as I've seen (and I've followed him since 2005) he is nearly, if not entirely flawless.
I remember a debate that raged back in the DNDN days. Walldiver, another poster who was almost never wrong regarding biostatistical issues was going after it with another poster. Iwfal weighed in. Someone scoffed and counter argued. Walldiver wrote back something to the effect, "Good luck" and "This is going to be good...!" It was.
Iwfal has always been generous with his knowledge. You can ask a question and he will answer it. That said, it's not any easier to understand much of what he says than it is to understand biostatistics in the first place!
Just saying, keep an open mind. He's a terrific resource for the board.
The article is 2010. Read it. Super. Thanks FTM and CJ. It was written/published 2010. I was listening to the May 2012 NYAS presentation again. Do you know, was that ever transcribed?
Thanks MJ. I read your article on KM curves and censoring. Was very good.
Iwfal, the MOS number originally reported was, I believe, 5.4 MOS. Now it's 5.6 months. When the number changed, I was a little confused as to how it could. I assumed somebody made a mistake and that they changed the number when they saw the mistake. Could, in fact, this change be related to that censoring issue?
I cannot believe that bavituximab won't go onto PIII. That's nearly a given in my mind. What's not a given is whether or not this is an issue in negotiations with Pharma. It could make a difference in the terms that we ultimately get in the deal.
Thing was, Garnick didn't jump in there either ... I wish he had.
You're probably right, but I didn't like the way things unfolded.
If you listen to the Q&A, they were asked several times to give granularity to the imbalanced arm issue in one way or another. They kept reiterating that there were not significant imbalances, but they didn't back up their assertion with any numbers or proof. When they were asked about specific issues like genetic markers they said they hadn't considered it because they figured PS was not a genetic issue. I found that unsatisfying. It's like the Asian issue - which, I would suppose, is also genetic. It could still cause an imbalance if not properly balanced. I'm not saying it would. But they should have known the answer to that question, not just say, we decided not to look at the issue.
In my business, you don't do a piece without taking it apart 100 times. I've never been asked a question that I hadn't already considered in the process of telling a specific story. I would consider it unprofessional.
That's my take. I just thought they came off as unprepared today. Hard to believe if they've been doing intense due diligence in partnership negotiations for such a long time...
and that is definitely IMVVVHO