Gone for good.
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I think if the PFS, MOS are about 50% better than control then your assumptions will be
proven wrong. A partner will be forth coming.
FWIW, here are my predictions. I am glad that I underestimated the ORR and PFS
for second-line NSCLC. For MOS here I go:
control 5.8 months
1 mg/kg 8.2 months
3 mg/kg 8.8 months
Yes, I do. I was thinking about the MOS of the control being determined to be less than 6 months.
If you look at the table of second-line NSCLC control arms (see post# 80336) the range of the MOS values
goes from 5.7 to 8 months. Let's assume it is 5.8 months, within the range, but on the low side. When the
calculations were done that determined the MOS < 6 months it was about 7 months since the
last patient was enrolled in the trial. I think at that time if the MOS of the two treatment arms
was 7 months or less then it would be known and reported. So I think we can safely assume that at the current
time for the treatment arms MOS > 7 months, at least, and counting, maybe more like 8 months.
A 50% increase would mean MOS is about 8.7 months, assuming the 5.8 months for the control arm.
Another thing I would point out is that the two results for PFS from the two doses are fairly close together.
If you combine them the number of samples doubles and reduces the noise (variance) in the data.
So in the end it could be possible to combine the two arms as a "treatment" arm and that compared with
the control arm could be statistically significant even if each arm by itself is not.
That is, if the two doses result in PFS, or MOS, that are close together so there is a lot of overlap between
them and so statistically they can't be separated then the results could be combined and treated as one treatment arm.
Entdoc, I don't want them to sell the company. How about a deal for first and second-line NSCLC
whole world, except US? Or something like that? That should be worth something.
There is so much more potential here I don't want to give it away.
Onward and Upward. Next thing I would like to see is interim data from the liver cancer trial,
and completion of enrollment for the pancreatic cancer trial. Then the MOS for second-line
NSCLC, follwed by MOS for first-line NSCLC. BRING IT ON!
If we had all the patient data we could compute the p values.
I think you need to know how the responses are distributed to do the calculations
I will predict MOS >= 9 months. Should know by July 4th as previously predicted.
I am already hearing the doubters say this is not statistically significant, at least for the ORR.
I do not think it has ever been said that this trial is powered to show statistical significance for ORR.
Placebo, my ass!
George, I am not sure what you mean here. You have a few facts incorrect. Roche did not buy out Avastin.
Roche had owned 56% of Genentech and then bought up the remaining 44%, so they got Avastin,
along with Rituxan, Herceptin, and all the rest of it. Approval for Avastin for metastatic breast cancer
was withdrawn because it did not extend the lives of patients when examined in a phase III trial.
Avastin had been given accelerated approval for this indication subject to phase III trial results showing
that overall survival was improved. Avastin has failed in some phase III trials for other indications, but
approval was only withdrawn for metastatic breast cancer.
YES. Maybe mojojojo might have something more to say about this.
As a follow up. It has now been 7.36 months (32 weeks) since the last patient in the trial was enrolled.
So now we know that every patient assigned to the control arm has been on the trial longer than 7.2 months,
the MOS mean of the 10 historic control arms (post # 77595). So yes, I think we will know what the MOS is,
at least for the control arm.
Interesting estimate of sales of biologic drugs for 2012 from May issue of Nature Medicine.
A long time ago I owned Immunex, which was later bought by Amgen. I remember that the drug
now known as Enbrel was written off by a lot of people during the course of its up and down development
period. It took like a decade before it was regarded as a success.
I do think they will have a very good estimate of MOS when they unblind the data, at least of the control group.
In case you didn't know where Peregrine comes from, and you thought it was a bird!
St. Peregrine Laziosi
Feastday: May 1
Patron of Cancer Victims
1260 - 1345
Peregrine Laziosi was born of a wealthy family at Forli, Italy, in 1260. As a youth he was active in politics as a member of the anti-papal party. During one uprising, which the Pope sent St. Philip Benizi to mediate, Philip was struck in the face by Peregrine. When Philip offered the other cheek, Peregrine was so overcome that he repented and converted to Catholicism. Following the instructions of the Virgin Mary received in a vision, Peregrine went to Siena and joined the Servites. It is believed that he never allowed himself to sit down for thirty years, while as far as possible, observing silence and solitude. Sometime later, Peregrine was sent to Forli to found a new house of the Servite Order. An ideal priest, he had a reputation for fervent preaching and being a good confessor. When he was afflicted with cancer of the foot and amputation had been decided upon, he spent the night before the operation, in prayer. The following morning he was completely cured. This miracle caused his reputation to become widespread. He died in 1345 at the age of eighty-five, and he was canonized by Pope Benedict XIII in 1726. St. Peregrine, like St. Paul, was in open defiance of the Church as a youth. Once given the grace of conversion he became one of the great saints of his time. His great fervor and qualities as a confessor brought many back to the true Faith. Afflicted with cancer, Peregrine turned to God and was richly rewarded for his Faith, enabling him over many years to lead others to the truth. He is the patron of cancer patients.
Exactly. The new paper in Neoplasia, and the posters at AVRO are the end result of research done a year ago.
These things aren't just whipped up at a moments notice to distract investors. If the NSCLC trials are failures
then every body will be asking where the back up plan is. Well it takes years to develop other plans, and this is part of it.
That is exactly why I said I have some doubts. While I expect the data to be good,
and I totally have confidence in the science and especially Dr. Thorpe's work,
there are always those unknowns out there. You know, the known unknowns!
Stuff like a total screw up at one of the reporting sites, the building burned
down and all the data was lost, that kind of thing. We will know soon enough.
The slides from the NYAS presentation are here
http://www.peregrineinc.com/images/stories/pdfs/nyasweb.pdf
Some of you laughed at the ARVO poster about HSV-1 Keratitis (Post #79661). However, this has potential as a drug. Note the following about ZIrgan, which the PGN632 was compared with. That is 48000 possible cases a year in the US. This is also something that could get approved relatively quickly as an opthalmic solution. Seems like something to license off to Allergan or J & J. Won't be big, but it is something.
Zirgan is the first innovation in the US topical ophthalmic antiviral class in 30 years
TAMPA, Fla., April 26 /PRNewswire/ -- Sirion Therapeutics, Inc., a privately held ophthalmic biopharmaceutical company, announced today that Zirgan™ (ganciclovir ophthalmic gel) 0.15% is now commercially available. Zirgan™, which was approved by the U.S. Food and Drug Administration in September 2009, is a topical ophthalmic antiviral indicated for the treatment of acute herpetic keratitis (dendritic ulcers).
.....
About Herpetic Keratitis
Herpetic Keratitis is the number one infectious cause of corneal blindness in the U.S. Herpes simplex virus infections are very common, with nearly 60% of the US population showing evidence of infection by age five. Approximately 1% of infected patients develop ocular outbreaks, with 20,000 primary cases of ocular herpes diagnosed in the US each year. After the primary infection, ocular HSV typically becomes latent until triggers such as stress, UV radiation, and hormonal changes reactivate the virus and cause recurrent outbreaks. Those recurrences account for an additional 28,000 cases per year in the US. The risk of blindness increases with the number and severity of recurrences, making prompt treatment imperative to limit corneal scarring and other more serious ocular complications caused by herpetic ulcers.
About Zirgan™ (ganciclovir ophthalmic gel) 0.15%
Zirgan™ (ganciclovir ophthalmic gel) 0.15% is indicated for topical ophthalmic use as a treatment for acute herpetic keratitis (dendritic corneal ulcers). Zirgan™ is an innovative topical antiviral therapy designed to specifically target herpes virus infected cells. Zirgan™ has been a leading treatment for corneal ulcers, under the brand name Virgan®, in Europe for more than 10 years.
Another one from ARVO meeting.
Presentation Abstract
Program#/Poster#: 6155/D1015
Abstract Title: Efficacious Clinical Outcome of an Ophthalmic Formulation of Phosphatidylserine- binding Monoclonal Antibody in a Rabbit Model of Acute HSV-1 Keratitis
Presentation Start/End Time: Thursday, May 10, 2012, 8:30 AM -10:15 AM
Session Number: 526
Session Title: Cornea/Anterior Segment Infection and Inflammation I
Author Block: Christian Clement1A, Hilary W. Thompson1B, Partha S. Bhattacharjee2, Harris E. McFerrin, Jr.2, Walter J. Lukiw3, Kara Corbin-Lickfett4A, Cyril J. Empig5, Kyle Schlunegger4, James M. Hill1A. AOphthalmology, BSchool of Public Health, 1LSUHSC, New Orleans, LA; 2Biology, Xavier University of Louisiana, New Orleans, LA; 3Neuroscience & Ophthalmology, Lousiana State Univ Hlth Sci Ctr, New Orleans, LA; AOphthalmology, 4Peregrine Pharmaceuticals, Inc., Tustin, CA; 5Peregrine Pharmaceuticals Inc., Tustin, CA.
Abstract Body: Purpose: Phosphatidylserine (PS) is a phospholipid found on the internal leaflet of the plasma membrane of normal cells which becomes exposed externally following infection with enveloped viruses. Monoclonal antibodies (mAbs) that recognize PS have the potential to bind infected cells, target them for clearance, and stop infection. The efficacy of the PS-targeting mAb PGN632 given topically was assessed in a rabbit model of HSV-1 keratitis.
Methods: Corneas were inoculated bilaterally with 2x106 PFU of HSV-1 strain McKrae following corneal scarification and placed in balanced groups based on slit-lamp examination (SLE) scores (5 rabbits per group). Treatment groups were (1) PGN632, (2) Zirgan® (0.15% ganciclovir), (3) combination of PGN632+Zirgan® (ophthalmic solution followed by ointment), and (4) vehicle. Treatments were given 4 times daily starting 3 days post infection (PI) and continued for 4 consecutive days. SLE was done daily in a masked fashion and eyes were clinically scored daily for epithelial keratitis, stromal damage, scleral inflammation, ocular neovascularization, eyelid inflammation, friability of vasculature, inflammatory discharge, and excessive tearing. Scoring was done each day prior to treatment. SLE and clinical symptomatic scoring were continued on PI days 8, 9, and 10, after drug treatment stopped.
Results: PGN632, Zirgan®, and combination PGN632+Zirgan® treatments resulted in significant reduction of corneal SLE scores (P < 0.05; p values from generalized linear model analysis of scores) and significantly lower clinical scores (P < 0.05) compared with the vehicle. No ocular toxicity was observed in any drug treatment group.
Conclusions: Our data show that the PS-targeting mAb PGN632 is at least equally efficacious compared with Zirgan® in reducing corneal SLE scores and minimizing the ocular clinical symptoms. By providing symptomatic relief in addition to reducing corneal SLE scores, PGN632 could become a drug of choice for treatment of ocular herpes.
CommercialRelationships: Christian Clement, None; Hilary W. Thompson, None; Partha S. Bhattacharjee, None; Harris E. McFerrin, Jr., None; Walter J. Lukiw, None; Kara Corbin-Lickfett, Peregrine Pharmaceuticals, Inc. (E); Cyril J. Empig, Peregrine Pharmaceuticals, Inc. (E); Kyle Schlunegger, Peregrine Pharmaceuticals, Inc. (E); James M. Hill, Peregrine Pharmaceuticals, Inc. (R)
Support: NIH EY06311
New uses for Bavi. ARVO Annual Meeting.
Presentation Abstract
Program#/Poster#: 443/D1120
Abstract Title: Anti-phosphatidylserine Antibodies As A Potential New Therapy Against Choroidal Neovascularization
Presentation Start/End Time: Sunday, May 06, 2012, 8:30 AM -10:15 AM
Session Number: 114
Session Title: AMD: New Drugs, Delivery Systems and Mechanisms
Author Block: Rafael Ufret-Vincenty1, Bogale Aredo1, Kaiyan Zhang1, Cynthia X. Wang1, Shusheng Wang1, Jose Pulido2, Philip E. Thorpe1. 1Ophthalmology, UT Southwestern Medical Center, Dallas, TX; 2Ophthalmology, Mayo Clinic, Rochester, MN.
Abstract Body: Purpose: Despite the dramatic changes in clinical outcomes brought by anti-VEGF agents, additional drugs directed against different targets in the neovascular process are needed. This may allow for combination therapies that could potentially eradicate choroidal neovascularization (CNV). In normal cells the aminophospholipid phosphatidylserine (PS) is almost exclusively localized to the inner leaflet of the cell membrane’s lipid bilayer. Endothelial cells of tumor neovasculature lose their capacity to maintain PS asymmetry. Anti-PS antibodies bind to the newly exposed phosphatidylserine in the outer leaflet of the tumor vascular endothelium, mediating antibody-dependent cell-mediated cytotoxicity, and causing the collapse of the tumor neovasculature. Radiotherapy increases the exposure of PS in tumor vasculature, enhancing the antitumor effects of anti-PS antibodies. We propose to evaluate if there is also exposure of PS in CNV, and if anti-PS antibodies can treat CNV.
Methods: We induced CNV in B6 mice using the laser model. Immunostaining for PS was done after perfusing mice with an anti-PS antibody and paraffin-embedding the eyes. We tested the effect of intravitreal anti-PS antibodies alone, or in combination with eye radiation, on the CNV size as measured with ICAM-2 staining.
Results: Paraffin sections of eyes perfused with an anti-PS antibody stained positive for PS. The staining co-localized with ICAM-2-stained CNV, demonstrating that PS was exposed on the choroidal neovascular membranes. The anti-PS antibody (11.31) led to a 52% reduction in the laser-induced CNV size (p=0.02) when injected intravitreally. We have established a system for irradiation of the eyes. We will show data on the effect of radiation alone or in combination with anti-PS antibodies on the neovascular complex.
Conclusions: Anti-phosphatidylserine antibodies may have therapeutic value in wet AMD alone or in combination with radiation or anti-VEGF agents.
This paper just came online this morning. The abstract has been out for a month.
It is very interesting and could expand the uses of anti-PS therapy to the neoadjuvant setting.
Vascular endothelial targeted therapy combined with cytotoxic chemotherapy induces inflammatory intratumoral infiltrates and inhibits tumor relapses after surgery
Brendan F Judy, Louis A Aliperti, Jarrod D Predina, Daniel Levine, Veena Kapoor, Philip E Thorpe, Steven M Albelda and Sunil Singhal
Neoplasia 2012, Volume 14, Issue 4
http://www.neoplasia.com/abstract.php?msid=5083
Note: all the other authors are from the Univ of Pennsylvania School of Medicine
Some highlights from the discussion section:
Note: cis = cisplatin, mch1N11 is the mouse chimeric version of 1N11, which is the fully human antibody.
Our data suggest that the mechanism is that cis, either directly or indirectly (i.e., by killing tumor
cells that then activates their associated vasculature), increases PS expression of the tumor vasculature.
This vascular PS presents a target for the mch1N11 antibody that binds and induces intense neutrophil
infiltration, leading to vascular disruption and tumor death. This process seems independent of the adaptive
immune system.
The results here demonstrate that targeting PS on tumor vasculature
can enhance the efficacy of cis and surgery without major toxicity.
The unique postoperative environment provides an ideal time to target
rapidly dividing cells with cis and developing vessels with mch1N11.
Bevacizumab (trade name Avastin) is a drug that blocks angiogenesis
and is currently in clinical use for a wide variety of tumors. However,
this agent has several contraindications surrounding surgery owing
to the increased risk of bleeding and wound healing complications
[4,25]. Although only a small animal model of surgery, we did not have
any of these morbidities with mch1N11. PS-targeting therapy specifically
targets and disrupts tumor vessels as opposed to bevacizumab
which is an anti-VEGF antibody. This present study contributes to
the previous preclinical and clinical studies showing the promising
nature of PS as a target molecule in recurrent cancers [26].
In conclusion, using a vascular endothelial–targeted therapy after
surgery shows significant promise to prevent lung cancer recurrences
after surgery. This approach is likely due to the unique window of
opportunity after surgery when there is a rapidly proliferating tumor
with significant capillary development and dependence on a source of
oxygen and nutrients. PS-targeting therapy during this time can incite
a strong inflammatory response, partially driven by neutrophils, which
can result in tumor cell killing and improved clinical outcomes.
Yes, I expect them to live longer, but I am human and I have doubts, just like everyone else.
Screw you. Some of us aren't as wealthy as you!
Today is exactly 7 months since the last patient was enrolled and began treatment in the second-line NSCLC trial.
It is hard to imagine that it could take this long to get the results, but here we are. I added another 1000 shares,
but honestly at this point I am resisting my expectations of something good about to happen. I don't want to be too
disappointed by not so good news.
RRdog, yes I agree on that. The big advantage that 124I-PGN650 will have is that it
should work on all tumors. The other imaging agents using an mAb linked to a
radioisotope are specific to a particular antigen that is not universally on tumors.
Yes, he mentioned the fact that the numbers involved are small and so ORR and PFS have a lot of noise
because they are harder to interpret than death (usually!). What I found interesting were the slides on the
radiation treatment with bavi and the imaging. I want to look at those more closely. I especially liked the
rotating image of the imaging results.
I am looking forward to the webinar with Thorpe at the NYAS on Tuesday. However, I don't expect anything
new to be announced by him. He is the academic scientist and not the one to announce results of Peregrine trials.
Instead, it will come by way of a PR early some weekday morning next month.
I am saying that by Memorial Day they will know ORR, PFS for sure.
It will be 7 months on May 6 since the last patient began treatment.
Since the historical mean of MOS of the control arms in the second-line NSCLC trials
is 7.2 months they probably will also know the MOS of the control and treatment arms too.
However, they will probably wait until some number, like 80%, of the patients have died
before they release the MOS numbers, which could be by Independence Day.
Remember that the trial started on June 4, 2010 so that half of all the patients
could already have died by now. It really depends on the distribution of when the patients
enrolled since the trial started. If they enrolled at a fairly uniform rate over that time then
I should be correct, but we don't know for sure. Assuming that the rate is uniform then 7.5
patients enrolled each month. So after the first 12 months, by June 4, 2011, 90 patients
were enrolled, which is 75% of the 120 goal. So by May 6, 2012 all of those 90 had at least
11 months pass since they enrolled. So I would guess that they could get a pretty good
estimate of the MOS for all the arms by Memorial Day.
Can't really bet on something we both agree on!
I hope so. For Memorial Day, let's say, as Fire Fox has stated, that the data is unblinded
on May 6, that will be 7 months since the last patient was enrolled, then leaving 3
weeks for putting it all together, takes it to Memorial Day. For Independence Day,
assume that in mid-June they start putting all the data together for the second-line MOS,
that will be just over 8 months since the last patient was enrolled. For Labor Day,
assume mid-August they start putting the data together for first-line MOS,
that will be just over 11 months since the last patient was enrolled in that trial.
So there you have it, by the end of the summer we could know all the numbers,
for better or worse.
Here are my guesses based on a holiday schedule.
Memorial Day - release of ORR, PFS for second-line NSCLC
Independence Day - release of MOS for second-line NSCLC
Labor Day - release of MOS for first-line NSCLC.
Clinical Trials updated for one of the phase I trials. Is the location at the University of Pittsburgh Medical Center new?
Bavituximab Plus Carbo and Pemetrexed in Chemo-Naive Stage IV Non-Squamous Non-Small Cell Lung Cancer (NSCLC) Subjects
http://www.clinicaltrials.gov/ct2/show?term=Bavituximab&recr=Open&rank=5
This upcoming meeting is available as a webinar for free.
Phosphatidylserine Asymmetry and Cell Survival: Therapeutic Applications in Cancer and Infectious Disease
Tuesday, May 1, 2012 | 1:00 PM - 5:00 PM
The New York Academy of Sciences
4:20 PM
Targeting Tumor Vasculature and Reactivating Tumor Immunity with Bavituximab
Philip E. Thorpe, PhD, UT Southwestern Medical Center
Go to this link and click on "Register for Webinar"
http://www.nyas.org/Events/Detail.aspx?cid=3a8f6210-f881-4364-b320-abc40b42c93d
Let's say that you are correct and on May 6, which will be 7 months since the
last patient started treatment, the trial results are unblinded. At that time they
will know everything, which includes the survival to that point. If the average MOS is
7.2 months for the control arm then they will know the MOS since the first patient
was enrolled on June 4, 2010. It may not be the final OS, but it will be close.
It might not be reported until it matured more, but they will have a very good idea.
Assuming that the MOS number looks good, it could be a selling point to anyone
who is interested in making a deal.
Thanks for the clarification on that. If Peregrine does not have any presentations at ASCO
this year then why time things for that week when there will be many PRs coming out.
Why not announce a week before?
Fire Fox, think there is any chance they would wait until they also could report the MOS?
Waiting until the end of June is still in the first half of the year. If you report ORR and
PFS and they aren't good, but the MOS is very good, then you are saved. However,
if ORR and PFS aren't good and you don't report MOS then the stock goes to zero, even
if later the MOS comes out as very good. Seems like it might be worth waiting
and report everything all at once. At least then you can judge the whole trial all at once.
I was just responding to the accusation about RRdog you made, I am not defending the
stock price or anything else.
Maybe he has nothing to say because there is nothing more to say until the
second-line NSCLC data comes in. Why respond to a bunch of baseless
rumors and the usual bitching? Just sell your shares and get it over with.