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Dr Cortez' discussion of ponatinib begins around the 6 min mark.
Yea, that's basically where I'm at too...anything this year would be a nice upside surprise.
In the elderly group the ORR wasn't significant and the PFS benefit was about 5 weeks. I don't think it's a slam dunk but I'm long CELGZ so I'm hoping it squeaks by.
>>Was there an ODAC meeting for this?
No, I don't think there was.
My concern is that even though OS was significantly improved (median 19.9 vs. 10.4 months, HR 0.583, p=0.009) in the over 70 group, this group did not meet the trials primary ORR endpoint....also the safety profile looks mixed.
CELG CELGZ Abraxane's NSCLC PDUFA date is tomorrow. The trial results were marginal. http://ir.celgene.com/phoenix.zhtml?c=111960&p=irol-newsArticle&ID=1701834&highlight= Does anyone think this has a chance of getting approved?
If they were going for a narrow label eg just T315I, approval would likely come faster . A 2nd line (fail one tki) label may take a bit longer but will be well worth it.
btw, I never suggested a date -whether Thanksgiving or any other.
It's called the Oncologic Drugs Advisory Committee. An ODAC panel is not required for approval but is often scheduled when the data is not clear cut.
The 60 day time clock started on September 28th not July 30th.(btw, it's 45 days if they are granted accelerated review)
For reference, the FDA reviewed Gleevec and Pegasys in four months; Kaletra was approved in 3.5 months. So, even with accelerated approval, 3 weeks is unlikely. Geez, the FDA hasn't even accepted the drug for review and you've already got it approved.
So, ponatinib is going to be approved in less than 3 weeks? Do you have any clue how the FDA approval process works?
Baker Boys....why would someone be afraid of a couple of piano playing brothers...do they have a large position that i should worry about?
remember to paddle home safely
If "they" are disappointed
>>philanthropist investments.
Does that mean gains are considered charitable giving for tax purposes? :)
Nice to see the ARIA upgrade to $30 but I still think a good case can be made that ponatinib is worth more than the $21 allocated to it in Merrill's model. First, peak sales of $566M is too low. There are 56,800 CML pts. Of these, 30% will eventually become resistant to current TKI's. Assuming ponatinib receives a broad 2nd line label, that gives them a target market of around 17,000 pts. Even if you assume that ponatinib only attracts the 40% of the 17,000 whose resistance is from mutations, they'll likely capture 6,800 pts - which is right around 12% of the total market.
The company will likely price ponatinib at $133k. Personally, I think premium pricing is the right way to go...at least until they get front-line approval and/or gleevec goes generic. So what's ponatinib worth? Well, 6,800 pts at $133k = $900M. Using the same 6X multiple Merrill used in their model, gets you to $5.4B and, with 166m shares outstanding, results in $32.50 pps attributable to ponantinib which is about $10 more than Merrill is currently modeling for ponatinib. Adding Merrill's $11/share for 113, $2/share in cash, and 14% for dilution, gives you an overall price target of right around $39 or 50% upside from current levels.
Furthermore, I would argue that ponatinib is going to have much greater success in front-line than is currently contemplated. The primary reason being is that instead of waiting for mutations to develop, leading cml specialists now recognize there may be a benefit to using the best option first. In fact there is now some evidence that"mutation may be present early in the disease and undergo expansion following elimination of their drug-sensitive counterparts." This changing treatment paradigm should only benefit ponatinib as it is currently the only TKI that works against all known bcr-abl mutations.
Clearly, non-squamous did not capture the high c-Met that the trial was hoping for. Thanks to the discussions on this board, i kept my exposure relatively small. It's disappointing to be statsig on PFS and yet have the trial stopped for futility.
***Note to self - try to avoid investing in a p3 trial without a confirmed P2 target and the same endpoint! (a lesson I should have learned with ridaforolimus, lol)
fwiw, the long enrollment is what has me sitting on my hands today instead of averaging down. I'll probably wait for the high c-Met subgroup analysis before I "set it and forget it."
>>Pucci's ruminations on Phase II and III trial designs in cancer are interesting to listen to.
I bet I wasn't the only one listening who thought if the ceo felt so strongly about running P2 and P3 with same endpoint then why the heck didn't he take his own advice. It would have saved us all a lot of $$$. MetMab's now got a clear runway in what looks to be a very good target.
Is this a paying job for them or do they just get free bananas?
Yea, looks like ARQL is going to open around cash value. brutal. the only consolation is that I hadn't fallen in love with the stock yet, lol. hopefully $CELGZ news will offset the pain a bit.
Me and you both. Obviously it's going to get crushed today but I'm hoping the post hoc will at least confirm the KRAS mutant target is still viable http://clinicaltrials.gov/ct2/show/NCT01395758
CELG Says ABRAXANE Met Phase III Primary Endpoint in Metastatic Melanoma
Celgene International Sàrl, a subsidiary of Celgene Corporation (Nasdaq: CELG) today announced results of its phase III, randomized, international study (CA033) of ABRAXANE (paclitaxel protein-bound particles for injectable suspension) (albumin-bound) in chemotherapy-naïve patients with metastatic melanoma. In the study, the primary endpoint was met with patients receiving ABRAXANE demonstrating a statistically significant improvement in progression-free survival compared to patients receiving dacarbazine (DTIC) chemotherapy.
The safety profile of ABRAXANE observed in the CA033 study is consistent with other ABRAXANE pivotal clinical trials. Data from this study will be presented at the Society for Melanoma Research (SMR) Congress 2012 in Los Angeles in November. Future regulatory and clinical strategies are being reviewed in light of these results.
The CA033 study is a Celgene-sponsored, open-label, controlled, randomized study comparing ABRAXANE to standard chemotherapy, DTIC, in patients with metastatic melanoma. DTIC is the only chemotherapy approved since 1975 by the U.S. Food and Drug Administration for metastatic melanoma. In the study, 529 chemotherapy-naïve patients were randomized to receive either ABRAXANE (150mg/m2 weekly for 3 out of 4 weeks) or DTIC (1000 mg/m2 every three weeks). The primary study endpoint was independently-assessed progression free survival. Secondary endpoints included overall survival, overall response rate and disease control, safety and tolerability.
ArQule and Daiichi Sankyo Announce Discontinuation of Phase 3 MARQUEE Clinical Trial in Non-Small Cell Lung Cancer
DMC Recommends Discontinuation of Study for Futility
WOBURN, Mass. & TOKYO, Oct 02, 2012 (BUSINESS WIRE) -- --No Unexpected Safety Findings from Interim Analysis
ArQule, Inc. ARQL -2.35% and Daiichi Sankyo, Co., Ltd. (TSE 4568) today announced that the independent Data Monitoring Committee (DMC) of the Phase 3 MARQUEE (Met inhibitor ARQ 197 plus Erlotinib vs Erlotinib plus placebo in NSCLC) trial recommended the study be stopped early following a planned interim analysis, when they concluded that the study would not meet its primary endpoint of improved overall survival. Although the interim analysis showed a statistically significant improvement in progression-free survival (PFS) in the intent-to-treat (ITT) population, this benefit did not carry over to overall survival. There were no safety concerns identified by the DMC to Daiichi Sankyo or ArQule during this interim analysis.
Although the MTD has not been reached, at least in ALK+ it certainly appears that 113 offers a stronger response and lower tox than LDK378 (which btw showed DLT at 400mg which also happens to be the active dose....not a good thing)
As far as EGFR goes it is too early to know, however, the PK data looked really good to me...especially in the 8L58R and T790M mutations. Your thoughts? http://bit.ly/V6K65V http://bit.ly/O0DRxG
Who cares? I think you'll find a more receptive audience on Yahoo.
Here are the slides from the AP26113 ESMO presentation http://bit.ly/TYjoNC
True, but there appear to be better targets than squamous/non-squamous...http://cancergrace.org/lung/files/2010/08/schiller-arq-197efficacy-by-subgroups.jpg and in the metmab trial http://cancergrace.org/lung/files/2010/08/schiller-arq-197efficacy-by-subgroups.jpg
However, that being said, I'm more than happy acquiring shares at ARQL's current enterprise value.
Yes. lol, the certainty with which some investors express their conviction, which I call "newbitude", can lead to some interesting exchanges. msg id=70391276
THLD - TH-302 data was presented at ESMO which showed a statsig 6mo PFS vs 3.6mo for gemcitabine alone, however the toxicities, especially at the 340mg level, are going to prove problematic.
http://biotechstrategyblog.com/2012/09/esmo-2012-th-302-pancreatic-cancer-survival-data-fails-to-impress.html/
Also, nice blurb at the end re: abraxane/CELGZ
LOL. at this point I'm not sure what the heck they are calling the "phase 2" but I may owe you a cold beverage.
Berger may have been referring to the fact that while they plan to run a treatment naive ALK+ cohort (potentially 1st line), in EGFR they are targeting 2nd line pts who are resistant to at least one prior EGFR inhibitor. http://1.usa.gov/UA4RlT
Hopefully we'll learn more tmrw morning but one thing to note is that even in 2nd line EGFR represents about 2X the ROS1 and ALK+ pts.
Dough, here's the complete post (it may not have been clear in the original post that the comments were coming directly from the Director of the FDA's Office of Hematology and Oncology Products)
-----------
Pazdur's Tale of Two Targeted Therapies
The Pink Sheet Daily. 2012 Sept 24, S Sutter
Offering his own version of Charles Dickens’ “A Tale of Two Cities,” FDA Office of Hematology and Oncology Products Director Richard Pazdur highlighted two real-world examples representing the best and worst of times in the quality of development programs for personalized cancer medicines.
Both therapies cited by Pazdur at a Sept. 14 conference on drug/diagnostic co-development are targeted at patients with chronic myelogenous leukemia who have the acquired BCR-ABL T315I mutation, which can create resistance to tyrosine kinase inhibitors approved for CML. However, the two drugs were worlds apart in strength of the efficacy data and reliability of diagnostic testing in pivotal trials.
Pazdur started out with the “worst of times” example, ChemGenex Pharmaceuticals Ltd.’s Omapro (omacetaxine) for patients who have failed treatment with Novartis AG’s Gleevec (imatinib).
In March 2010, FDA’s Oncologic Drugs Advisory Committee voted 7-1 that omacetaxine should not be approved without a well-characterized in vitro diagnostic for identifying the small subset of CML patients with the T315I mutation.
FDA and ODAC members were critical of the clinical development program, with agency review staff asserting that ChemGenex failed to develop an adequate assay for differentiating which patients carried the mutation even though it was pursuing an indication that would make omacetaxine, a highly toxic injectable chemotherapy agent, second-line therapy ahead of other available TKIs, specifically Bristol-Myers Squibb Co.’s Sprycel (dasatinib) and Novartis’ Tasigna (nilotinib).
Physicians treating patients in the company's 66-person clinical trial used multiple techniques for determining the presence of the mutation. Many samples were sent to commercial labs in the communities where the patients were treated, and more than one-third of patients never had their T315I mutation diagnosis confirmed by the central labs before being included in the trial. The two central labs used different testing methods for the mutation and different cut-off points for determining when a patient was considered resistant to TKIs.
The review ended with a “complete response” letter that required the company to validate its existing tissue samples against an assay that FDA considers to be valid, ChemGenex said. The company was subsequently acquired by Cephalon Inc., which became part of Teva Pharmaceutical Industries Ltd. last year.
Pazdur said omacetaxine had relatively modest activity. “It was very important to have a really well-defined in vitro diagnostic to identify patients with this disease because if you misdiagnosed the patients as having this mutation, you were denying them potentially a very effective drug” in the existing TKIs, he said. “If this drug really went on the market without a really well-defined in vitro diagnostic, one could do more harm than good.”
The oncology office director then moved on to his “best of times” example. Although Pazdur declined to identify the drug since it is currently under FDA review, it’s evident from his remarks that the compound is Ariad Pharmaceuticals Inc.’s BCR-ABL inhibitor ponatinib, which was submitted as part of a rolling NDA in July for treatment of patients with resistant or intolerant CML and Philadelphia chromosome-positive acute lymphoblastic leukemia. Simultaneous with the NDA submission, Ariad’s diagnostic development partner, MolecularMD Corp., submitted a premarket approval application for a companion test for the BCR-ABL T315l mutation.
“The basic science behind this drug is, I would call, relatively exquisite. It was very well done,” Pazdur said. “This drug has very, very good activity in patients that have this acquired genetic mutation, but it also has very impressive activity in patients that do not have the mutation, that have had disease that [is] refractory to imatinib, in other words that would be candidates for dasatinib and nilotinib. One could question whether one needs an in vitro diagnostic here because the activity of this drug is so impressive … in patients that have the mutation as well as those that do not have it.”
On Sept. 18, four days after Pazdur’s remarks, Ariad and MolecularMD announced that the companion diagnostic PMA was voluntarily withdrawn.
The companies said MolecularMD was recently informed by FDA’s Center for Devices and Radiological Health that the test is no longer considered to be a companion diagnostic because such a designation requires that it provide information essential to the safe and effective use of the drug.http://www.oncologystat.com/news/Pazdurs_Tale_of_Two_Targeted_Therapies.html
initial thoughts:
The ALK+ response met what were very high expectations. I suspect that both response rates and duration will continue to improve as the dose escalates. There aren't a lot of egfr data points yet but I'm encouraged that they are dosing at 240mg and are showing activity. The brain mets response was nice to see however it's important to note that LDK378 and CH5424802 also showed brain met activity.
Will AP113 be ALK+ NSCLC best-in-class? In crizotinib resistant pts, AP113 showed a 67% response rate and a 6 month duration while LDK378 had less than a 50% (21/45) response rate and a 7.4 month duration. Once the MTD is determined, I suspect AP113 will demonstrate both greater efficacy and duration of response.
CH5424802 is the one to keep an eye on, especially in treatment naive pts where it achieved an 85% response rate but I'm not sure what the duration of this response has been. Also, in comparison to the AP113, the CH5424802 trial appears to have a somewhat more restrictive enrollment criteria which makes a direct comparison more difficult, however, it is worth noting that in the AP113 trial both of the evaluable ALK+ naive patients achieved a PR. At this point, we simply need more data points at AP113's MTD but based on these very early results, it appears that AP113 will exceed LDK378 in resistant pts and at least meet CH5424802 in the treatment naive population.
Overall, the results, while early, are certainly compelling.
worth a listen around the 3:18 mark a leading expert in CML calls ponatinib a "great advance" and expects that it will be used in a front-line setting.
I've been channeling my "inner" BTH lately in the hopes that this pig will go higher.
sorry i missed that one, i'll try to do a better job, lol.
As far as creating long-term shareholder value goes, a partnership deal with NVS would not be my first, second, third, or any choice. Ariad is well beyond the partnership stage.
Any interest in running a board survey on ponatinib's approval date?
That's all well and good but those recommendations aren't going to have any impact today.