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The AP26113 trial excludes patients with brain mets
oops, just realized that you were asking about ponatinib and not ap26113.
The AP26113 trial excludes patients with brain mets so, at this point, it's unknown, however LDK378 did show some activity so I wouldn't rule it out.
Complete enrollment is expected to take 18 months but its going to take time to ramp up so let's say the half-way point is reached closer to 11 months. That would put the key interim analysis sometime right around June 2014....conveniently right before ASCO.
The trial is powered to show a 15% absolute improvement in MMR over gleevec in newly diagnosed CP patients. As the press release points out the MMR in the tasigna and sprycel trials was 22% and 28%, respectively. Using the average in these two trials of 25%, would require ponatinib to achieve a 40% MMR to meet the primary endpoint. For reference, in the phase 2 trial, ponatinib achieved a 37% MMR in just over 10 months in patients who had already failed at least 2 other tki's. I like our chances, lol.
There are approx 1.6 million new lung cancer cases each year. Of these, about 15% are in the US. So, ROW is approx is 1.37 million cases. 90% are NSCLC and 4%, or almost 50,000 are ALK+. So, purely on the basis of the number of new cases, non-US represents a significant potential market.
Well, maybe not as good as I originally thought. ALK plus EGFR is 6% of ALK+ population not 6% of NSCLC as I originally calculated (thanks for the heads-up, Peter).
In my original post, I thought i was being conservative by assuming ALK+ plus ALK/EGFR in total was 6% of NSCLC, or 11,500 patients in US, but in actuality the number is around 8,600 which would make it closer to a billion dollar market in the US before factoring in rest of world, ROS1, increase in patients from improved survival rates, and EGFR opportunity.
Small data set aside, if the 6% number holds true then in just the U.S. this subset alone is a $1billion+ opportunity as it stands today, and, depending on the impact AP26113 has on survival rates, could be much larger.
There are 226,000 new case of lung cancer diagnosed in the US each year. Of these, 85%-90% are NSCLC. So, potentially 11,500 express ALK or both ALK and EGFR. Assuming AP26113 is able to achieve the same $9600/month pricing of crizotinib, then the potential market is $1.3 billion in the U.S. Furthermore, this does not factor in the positive impact the drug will likely have on overall survival rates (today the 5 year survival rate in NSCLC is around 15%).
On top of this, an additional 2% of patients are ROS1 which AP26113 also potently inhibits (see this years AACR Poster http://bit.ly/QxjMjb )
The ALK/ALK+EGFR/ROS1 could easily be a $2 billion dollar market in the US alone and that's not even considering whatever opportunity AP26113 has in the 10-15% of EGFR patients.
Good point with regard to wild-type EGFR but AP26113 seems tailor-made for the subset of treatment naive NSCLC patients with ALK rearrangements that also have concurrent EGFR activating mutations. http://www.ncbi.nlm.nih.gov/pubmed/21791641
LDK378 appears to be about six months ahead of AP113 but I guess the $2 billion question is which one will ultimately be the better drug. I went back and looked at the asco data and found that in the 26/33 pts who failed crizotinib and received >400mg dose, LDK378 had an 81% response rate. However, the overall response rate for all 33 pts who received >400mg dose was only 67% which means that in nsclc pts who had not received crizotinb (and therefore i would assume did not express ALK), the LDK378 response rate was less than 15%. Perhaps AP113' dual alk/egfr inhibitors will offer an advantage in overall response as well as durability given that such a high percentage of pts develop the T790 mutation against which LDK378 would presumably have little effect.
Crizotinib has shown a remarkable response rate in NCSLC with the ALK gene rearrangement. Unfortunately the response has not been durable and most patients develop resistance within 9-12 months. NVS (LDK378)and ARIA (AP26113) are the two drugs with the most potential in this space.
While the LDK378 results presented at ASCO were impressive, as long as AP113 is able to show similar efficacy with a better safety profile, AP113 will clearly offer the best treatment option. And, yes, I do believe AP113 has the potential to show better efficacy outright than LDK378 - at least in part because AP113 inhibits both alk and egfr which are both expressed in a subset of NSCLC patients.
"LDK378 showed substantial activity in patients with ALK-positive NSCLC. The overall response rate was 81% among the 26 patients previously treated with crizotinib who then received LDK378 at doses of 400 mg per day or greater. The objective response rate among all 33 patients with NSCLC receiving at least 400 mg per day was 67%"
"In the dose-escalation phase of the study, patients received between 50 mg and 750 mg of LDK378 per day. Most patients (83%) received at least 400 mg, the dose thought to be required for clinical activity. The maximum tolerated dose was 750 mg per day, although dose-limiting toxicities were observed in patients receiving 400 mg per day and higher. Common adverse events included nausea (59%), vomiting (54%), diarrhea (48%), fatigue (21%), and dyspnea (16%). Serious adverse events included one case each of transaminase elevation, vomiting, dehydration, and interstitial lung disease. These were all reversible after stopping treatment."
As far as 113 goes, the safety data is the whole ballgame. NVS's alk-inhibitor is already in P2 and has shown good efficacy but the safety data wasn't great (DLT's were observed at dose levels thought to be required for clinical activity). The upcoming data will help us better understand whether this is a class effect or drug specific. If AP113 can show similar efficacy with a better safety profile then AP113 will be the best in class ALK inhibitor. And that doesn't factor in any additional upside from the EGFR inhibitor which has shown potent inhibition against the T790M mutation.
Basically the move from $5 on was all ponatinib. back of the envelope, my guess is the market is currently valuing ponatinib at something around $14, rida prob a $1, and around $3/4 for AP113. Does that sound right to you?
TSRX CEO discusses the advantages the GAIN Act provides antibiotic drug developers http://www.xconomy.com/san-diego/2012/07/11/in-search-of-meaningful-gain-in-renewal-of-prescription-drug-act/?single_page=true
If you post a copyrighted analyst report, word for word, then you are likely infringing on their copyright. The facts or ideas contained within the report are not subject to the copyright so "you are free to report the facts and ideas embodied in another person's article or web page. Copyright only protects the expression — the combination of words and structure that expresses the factual information — not the facts themselves." (source EFF)
I'm not an attorney but my understanding is that adding your own commentary or analysis to the quoted work constitutes fair use. So please keep those analyst updates coming :)
Two different things. This was a cancer patient's personal, copyrighted blog.
Ethics aside, the post you copied was copyrighted which means that unless you had the authors permission, you had no right to re-post it in the first place.
Anyone who re-posts a cancer patient blog needs to check their moral compass. Trying to take advantage of someones pain for financial gain is just flat out wrong.
This has been discussed on this board many times before but it appears some still need to learn the lesson.
http://investorshub.advfn.com/boards/read_msg.aspx?message_id=75258788
http://investorshub.advfn.com/boards/read_msg.aspx?message_id=75282229
http://investorshub.advfn.com/boards/read_msg.aspx?message_id=75259715
http://investorshub.advfn.com/boards/read_msg.aspx?message_id=75268125
If you've been invested since late 2008, then congrats you caught the bottom. Since Dec 31, 2008 the stock has returned 1945%. In comparison the SP500 closed at 903.25 on 12/31/2008 and, based on today's close of 1,334.76, has generated a 48% return. So, over the time period that you have owned the stock, ARIA has outperformed the overall market by 40 times. Given that performance, your complaints seem completely misplaced.
I suspect most of us could care less about short-term price movements and are just biding time until the AP113 results are released at the beginning of Oct. Until then, my guess is that we'll continue to trade in a fairly narrow range and remain tied to the macro events driving the overall market. So, my advice is to try to enjoy the summer!
Now that the momo players have "discovered" cprx, there will be a lot more volatility but I fully expect the pps to continue run into the trial news. The next few months should prove a lot more interesting than the last couple, lol.
At this point, I'm not sure whether management is clueless (message 136825) or deceptive (message 144967). Yet, the stock has almost doubled in the past month and still sports a $350mm market cap.
How to Tell When A Drug Company Fibs About Clinical Trial Results - By Adam Feuerstein
"Ride along with me as I pick apart Osiris' statements regarding the Prochymal heart attack study. Interpreting clinical trial results with a skeptical eye is a crucial tool for all biotech investors, so apply these skills universally whenever a drug or biotech company tries to convince you that its drug works. Hopefully, you'll find most companies are telling the truth, but sadly and too often, bullish pronouncements about boffo clinical trial data are just spin jobs ginned up to plaster over problems and bad data."
http://www.thestreet.com/story/11605008/1/how-to-tell-when-a-drug-company-fibs-about-clinical-trial-results.html
Xalkori has shown phenomenal response rates in ALK+ NSCLC but, so far, that hasn't translated into "improvements in patient reported outcomes or survival with XALKORI."
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Pfizer Announces Positive Results From Phase 3 Study PROFILE 1007 Evaluating XALKORI® (crizotinib) In Previously Treated Patients With ALK-Positive Advanced Non-Small Cell Lung Cancer
NEW YORK--(BUSINESS WIRE)--
Pfizer Inc. announced today that the PROFILE 1007 study met its primary endpoint, demonstrating that XALKORI® (crizotinib) significantly improved progression-free survival (PFS) when compared with pemetrexed or docetaxel, in previously treated patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC). PROFILE 1007 is the first randomized Phase 3 study in ALK-positive advanced NSCLC patients.
"These results are important because they demonstrate, for the first time, that XALKORI is superior to standard chemotherapy in prolonging survival without progression in patients with previously-treated ALK-positive advanced NSCLC," said Dr. Mace Rothenberg, senior vice president of Clinical Development and Medical Affairs for Pfizer's Oncology Business Unit. "This study provides further support for the precision medicine approach to drug development being taken at Pfizer by demonstrating how knowledge about the underlying genetic abnormalities within a cancer can be used to improve the standard of care for that disease."
The adverse events observed on crizotinib and chemotherapy in PROFILE 1007 were generally consistent with their respective known adverse event profiles. Full efficacy and safety data from this study will be presented at an upcoming medical congress.
Ongoing Studies of XALKORI®
Pfizer is committed to the development program for XALKORI, and continues to study the therapy in several ongoing trials including PROFILE 1014 (A8081014), a Phase 3, open-label, randomized, two-arm study to evaluate the safety and efficacy of XALKORI in comparison with pemetrexed plus cisplatin or carboplatin in patients previously untreated for ALK-positive advanced NSCLC.1 In addition, PROFILE 1005 (A8081005)is an ongoing Phase 2 open-label, single-arm study on the efficacy and safety of XALKORI in patients with ALK-positive advanced NSCLC who have failed more than one line of treatment with prior chemotherapy.2 For more information on these clinical trials, please contact the Pfizer Oncology Clinical Trial Information Service at 1-877-369-9753 (US/Canada), via email at PfizerHPTrials@emergingmed.com or visit www.pfizercancertrials.com .
About Non-Small Cell Lung Cancer
Worldwide, lung cancer is the leading cause of cancer death in both men and women.3 In Europe, lung cancer accounts for 20 percent of all cancer-related deaths.4 NSCLC accounts for about 85 percent of lung cancer cases and remains difficult to treat, particularly in the metastatic setting.5 Approximately 75 percent of NSCLC patients are diagnosed late with metastatic, or advanced, disease, where the five-year survival rate is only 6 percent.6,7,8
About XALKORI®
XALKORI received an accelerated approval by the U.S. Food and Drug Administration (FDA) for the treatment of locally advanced or metastatic NSCLC that is ALK-positive as detected by an FDA-approved test. This indication is based on response rate. There are no data available demonstrating improvements in patient reported outcomes or survival with XALKORI. XALKORI also has received approval in a number of other countries including Canada, Korea, Japan and Switzerland.
XALKORI has played a significant role in advancing the treatment of personalized medicine in NSCLC and has rapidly become a standard of care in ALK-positive advanced NSCLC. XALKORI blocks signaling in a number of cellular pathways that are believed to be critical for the growth and survival of tumor cells, which may lead to stabilization or regression of tumors.3,9 Alterations in the ALK gene are believed to be a key driver of tumor development in cancers like NSCLC.10 Although ALK rearrangement is known to occur more frequently in patients with non-squamous cell carcinoma and histories of light or never smoking, it has also been shown to occur in smokers and in patients with squamous cell carcinoma histology.11 Alterations in the ALK gene can occur independent of age, gender, ethnicity and smoking history.12
XALKORI has demonstrated inhibition of c-MET, the hepatocyte growth factor receptor, and its activity is under investigation.12 XALKORI has also been shown to demonstrate a response in a Phase 1 trial in advanced NSCLC patients whose tumors have the ROS-1 gene rearrangement and its activity is continuing to be studied in this patient population.13
For more information and full prescribing information please visit www.XALKORI.com .
Important XALKORI® Safety Information
Drug-induced hepatotoxicity with fatal outcome has occurred. Transaminase elevations generally occurred within the first 2 months of treatment. Monitor with liver function tests including ALT and total bilirubin once a month and as clinically indicated, with more frequent repeat testing for increased liver transaminases, alkaline phosphatase, or total bilirubin in patients who develop transaminase elevations. Temporarily suspend, dose reduce, or permanently discontinue XALKORI as indicated.
XALKORI has been associated with severe, life-threatening, or fatal treatment-related pneumonitis in clinical trials with a frequency of 4 in 255 (1.6%) patients. All of these cases occurred within 2 months after the initiation of treatment. Monitor patients for pulmonary symptoms indicative of pneumonitis. Exclude other causes and permanently discontinue XALKORI in patients with treatment-related pneumonitis. QTc prolongation has been observed. Avoid use of XALKORI in patients with congenital long QT syndrome. Consider periodic monitoring with electrocardiograms (ECGs) and electrolytes in patients with congestive heart failure, bradyarrhythmias, electrolyte abnormalities, or who are taking medications that are known to prolong the QT interval. Permanently discontinue XALKORI for grade 4 QTc prolongation. XALKORI should be withheld for grade 3 QTc prolongation until recovery to = grade 1. Permanently discontinue XALKORI if grade 3 QTc prolongation recurs.
Detection of ALK-positive NSCLC using an FDA-approved test, indicated for this use, is necessary for selection of patients for treatment with XALKORI.
XALKORI can cause fetal harm when administered to a pregnant woman based on its mechanism of action. Women of childbearing potential should be advised to avoid becoming pregnant while receiving XALKORI. If the patient or their partner becomes pregnant while taking this drug, apprise the patient of the potential hazard to the fetus.
Among the 397 patients for whom information on deaths and serious adverse reactions is available, deaths within 28 days of the last dose of study drug occurred in 45 patients. Ten (2.5%) patients died within 28 days of their first dose of study drug. Causes of death included disease progression (32 patients), respiratory events (9), and other (4).
Safety of XALKORI was evaluated in 255 patients with locally advanced or metastatic ALK-positive NSCLC in 2 single-arm clinical trials (Studies A and B). The most common adverse reactions (=25%) across both studies were vision disorder, nausea, diarrhea, vomiting, edema, and constipation. Grade 3-4 adverse reactions in =4% of patients in both studies included ALT increased and neutropenia.
Vision disorders including visual impairment, photopsia, vision blurred, vitreous floaters, photophobia, and diplopia were reported in 159 (62%) patients in clinical trials. Consider ophthalmological evaluation, particularly if patients experience photopsia or experience new or increased vitreous floaters. Severe or worsening vitreous floaters and/or photopsia could also be signs of a retinal hole or pending retinal detachment. Advise patients to exercise caution when driving or operating machinery due to the risk of developing a vision disorder.
BTH is one of a kind...however if you think it'll help, i'll be more than happy to throw in a few PIG and POS references for good measure.
True, I'm not considering the location of Ariad's HQ relative to NVS - apparently, that alone could add BILLIONS of value in just weeks!!! ;)
Either of those events occurring by your 9/30 date is as likely as a lottery win.
If you set a Stop/Loss within 1% of a ten year high then you deserve to lose your shares.
U.S. cancer survivors to rise by a third by 2022
Thu Jun 14, 2012 10:03am EDT
(Reuters) - The number of Americans living with cancer will increase by nearly a third to almost 18 million by 2022, according to a report released on Thursday by the American Cancer Society and the National Cancer Institute.
Researchers found that even though the incidence rates of cancer are decreasing, the number of cancer survivors is on the rise due to a growing - and aging - U.S. population. The incidence of cancer rises dramatically with age.
The report concluded that the expanding population of cancer survivors makes it increasingly important that the medical community understand their unique healthcare needs.
http://www.reuters.com/article/2012/06/14/us-usa-cancer-projections-idUSBRE85D0Y720120614