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The oddest thing about this whole debate is the technology that would prevent all concerns of outcrossing, MON's Terminator technology, was the first target of the "environmentalists".
This issue is where Greenpeace jumped the shark.
AMGN-BioVex
Best line about this: "Amgen is so arrogant they believe they can fix anything."
The data from OncoVax are secondary. I doubt they'll ever be able to manufacture it at commercial scale.
AMGN acquisition of BioVEX is one of those, "Wait, really?" things.
This is a replication-competent, genetically-engineered herpes virus. I have to wonder how the FDA and especially EU regulators are going to look at this. Does the company have data showing their drug won't recombine with wt HSV to create some new critter? What about the recent data suggesting GMCSF is not beneficial? Has anyone discussed the need for a REMS due to the HSV base?
Perhaps BioVex has done all their work here, but given they jumped from essentially a 50-patient Phase I/II to a big Phase III I rather doubt it.
It will be interesting to see if this bid awakens investor interest in the space. If so, ONCY might get some love.
The issue of defensin resistance is well discussed in the literature (and a whole section of our initiation piece, FYI).
There is a group of scientists in France who also insist this is a bad idea. They ran their version of defensin peptides out to 100s of resistance iterations before they started to see resistance. Buried in their papers, which conclude this presents an important medical/social issue for these kinds of drugs, is that none of the resistance strains would likely be able to survie or reproduce.
For reference, all other antibiotics create viable resistant strains in under 15 passes through the standard resitance protocol (company info). PMX-30063 is above 30 now and still no viable resistant strains.
We identified this as a potential regulatory issue. It is, in our view, highly unlikely to prevent approval of the drug in the US or the EU (with the possible exception of France because, well, who can tell). At worst, it would limit use of the drug to last-line defense in acute MRSA. This is still a sizable market, of course, as complications from MRSA cost US hospitals some $20B by some estimates and add $5B to taxpayer-supported public healthcare expenses.
What is interesting about PMX-30056 is a completely different mechanism of action. To become resistant, bacterial cells would need to change their charge and generate a completely different lipid shell. Since all bacteria everywhere have thos two things in common, and have since the beginning of bacteria as far as we know, it's hard to conceive of an escape mechanism.
I'm not suggesting resistance is impossible to develop. Biology of bacteria are sneaky that way. There are good scientific arguments concerning why this is unlikely to happen.
I'd like to think there was some other reason, if only because I'd like to think GSK exectuvies were not that stupid.
OTOH, I've usually lost more by assuming big pharma BD people are smart than by assuming they are stupid.
It is certainly a puzzle. Fortunately, we'll get more data in a month and then even more data in early June.
ALTH Translated: "We need to run very fast before SGEN takes 25% of our market."
BMY knew the Phase II data presented at ESMO before bailing. Their last look before bailing was not as many patients as ended up being presented, but the signal was clearly there.
The explanation given is accurately retold. BMY was absolutely convinced around that time ipi was going to rule the world in prostate and was about to launch a worldwide study in M1 disease. They might still be convinced, but that study won't launch or result in an approval in the US now that Provenge has been approved without some significant Phase I/II work. Dendreon wants no part of such a study in the early launch because of the significant side effects of ipi.
The DSMB is responsible for adjudicating safety in both the trial and control arms. If the results are so clearly lopsided that a placebo-based control arm in a serious disease is getting hurt, they'd stop the trial even without a formal interim efficacy analysis. I've seen presentations of co-op group studies in cancer where this was the case.
CTIC halted the trial because of financial considerations. Says so in their filings. It had nothing to do with efficacy.
This said, I agree the FDA would look askance at any reguistration trial stopped early for efficacy without a planned interim analysis. I can't think of a registration trial where this happened, though I seem to recall the stop to the Nexavar trial was not at a formal interim analysis point. I might be wrong on that. But in co-op group trials, DSMBs will terminate a trial or remove arms or remodel arms do to outperformance even without interim stopping analyses.
Yup. I continue to believe that by preventing HDL from offloading, CETP inhibition creates dysfunctional HDL.
I'm still trying to get my head around the large reported increase in apo-a1 in the anacetrapib NEJM paper, but getting closer after talking with some experts in the field.
They are now theorizing a secondary apo-a1 generation signal -- a sort of a positive feedback loop. Since apo-a1 is rsponsible for HDL creation, but also larger HDL has more apo-a1 hanging off it, they think there is an unknown feedback loop caused by more, larger HDL molecules.
This still bends my head a little, because it would mean there is a apo-a1 creation pathway not intended to help creat more HDL, but take up stations on HDL molecules.
This begs the question, how do they know the difference in wha they are supposed to do.
Of course, as I'm sure Dew is itching to point out, the apo-a1 increase seen in the anacetrapib trial more simply means my theory is full of crap :)
D
According to the company, this is a unique structure. If it works as they expect (the piece at the bottom actually implies a two-sided trade), it will be how converts are done going forward.
It is true they did not have an SPA. We'll see what happens at the FDA. Maybe the "rational" market has it right and maybe they don't.
Yup
CORT is Alan's stock, and his sense is the NVS drug is going nowhere because of the metabolic side effects. We need to do more research on this. NVS continues to stonewall us in our requests to get copies of the scientific presentation from the EU meeting. NVS probably focuses on Europe to try and get a marketing lead on whomever Corcept partners with for ex-NA sales.
Corcept's Corlux succeeds in Cushing's Syndrome
http://finance.yahoo.com/news/Corcept-Therapeutics-iw-522291991.html?x=0&.v=1
MENLO PARK, CA--(Marketwire - 12/22/10) - Corcept Therapeutics Incorporated (NASDAQ:CORT - News) today announced positive top-line results from its Phase 3 study of CORLUX for the treatment of Cushing's Syndrome. The study evaluated the response of two patient groups to CORLUX treatment: one included patients who were glucose intolerant and one included patients who were hypertensive. Statistically significant improvement in the primary endpoint was achieved for both groups: with 60% responding in the glucose intolerant group and 43% in the hypertensive group. An initial review of safety data indicates that CORLUX was well tolerated by Cushing's Syndrome patients in this Phase 3 study. "The results of the study demonstrate that CORLUX has the potential to become an important treatment option for patients suffering from Cushing's Syndrome," said Joseph Belanoff, M.D., Chief Executive Officer of Corcept. "We remain on track to submit a New Drug Application (NDA) to the FDA for CORLUX in Cushing's Syndrome by the end of the first quarter of 2011 and continue to work toward our goal of making CORLUX available to patients with this severe disease."
Primary Endpoints Met in Both Patient Groups
Each group in the study had its own primary endpoint. The primary analysis is a responder analysis. In the "glucose intolerant group" (patients with diabetes or carbohydrate intolerance) a responder was defined as a patient who achieved a 25% or greater improvement in glucose tolerance as measured by a standard 2-hour glucose tolerance test at 24 weeks (or at the early termination visit) compared to baseline. In the "hypertension group" (patients with a diagnosis of hypertension) a responder was defined as a patient who achieved a 5 millimeter or greater improvement in diastolic blood pressure at 24 weeks (or at the early termination visit) compared to baseline.
The protocol for the trial dictates that if a sufficient number of patients in either the glucose intolerant group or the hypertension group are responders, such that the lower limit of the exact one-sided 95% binomial confidence interval (CI) for the responder rate is greater than 20%, then the trial will have demonstrated efficacy for the treatment of Cushing's Syndrome. The calculation, which was predetermined in the study design, is based on analyzing the response rates in a modified intention to treat group (mITT) defined as those patients treated for at least 30 days (the mITT group).
* 15 of 25, or 60%, of patients in the glucose intolerant group responded to treatment with CORLUX, significantly higher than the 20% hurdle rate (lower bound of the 95% CI = 41.7 which equates to p < 0.0001).
* 9 of 21, or 43%, of patients in hypertension group responded to treatment with CORLUX, significantly higher than the 20% hurdle rate (lower bound of the 95% CI = 24.5 which equates to p < 0.01).
CORLUX Was Well Tolerated In The Trial
CORLUX was well tolerated in the trial population. Although the detailed analysis of the safety data from the study has not yet been completed, the tolerability of CORLUX in the treatment of Cushing's Syndrome in the Phase 3 study met our expectations. Adverse events related to treatment included symptoms of adrenal insufficiency, endometrial thickening, and hypokalemia, all of which were consistent with earlier published reports. The majority of the serious adverse events (SAEs) reported in the study were not related to CORLUX treatment, as determined by the clinical investigators. Of those that were related to treatment, all resolved with clinical management. We plan to present detailed safety data at scientific conferences during 2011.
Ninety percent of the patients who completed the Phase 3 study opted to enter the long-term extension study.
About the Phase 3 Trial Design
The Phase 3 trial was a 50-patient open-label study in endogenous Cushing's Syndrome patients conducted at 17 clinical sites in the United States. Patients met the trial enrollment criteria if they were either not eligible for, had failed or had relapsed from surgery and were glucose intolerant or were diagnosed with hypertension at entry. Patients in the Phase 3 study were placed in one of two groups: those with glucose intolerance and those who were diagnosed with hypertension but were not glucose intolerant. In the trial, each patient's CORLUX dose was titrated by their study investigator to the level necessary to achieve clinical benefit. The FDA indicated that this trial may provide a reasonable basis for the submission of an NDA for the treatment of endogenous Cushing's Syndrome.
In addition to the primary endpoints described above, the key secondary endpoint in the trial was global clinical improvement, designed to capture the broader clinical benefit CORLUX may confer in this patient population. This endpoint is based on the evaluation of broader clinical outcomes by a Data Review Board, an independent three-member panel of academic physicians with expertise in Cushing's Syndrome. Data on this key secondary endpoint is expected to be available in the first quarter of 2011.
Additional secondary measures of efficacy include changes from baseline to the end of the study in fasting plasma glucose, hemoglobin A1c (HgbA1c), change in glucose lowering medications, systolic blood pressure, change in antihypertensive medications, body composition, weight, bone turnover and bone density, cognitive/psychiatric assessments, metabolic functions, Quality of Life (SF-36 questionnaire), muscle strength and physical function. Detailed data, including data on these secondary endpoints is expected to be announced at scientific conferences during 2011.
CORLUX Regulatory Status Update
Corcept is planning to submit an NDA to the FDA late in the first quarter of 2011 based on the positive results of this Phase 3 study. The final Phase 3 trial design and our statistical analysis plan reflect the feedback Corcept received in discussions with the FDA.
CORLUX was granted Orphan Drug Designation by the FDA for the treatment of endogenous Cushing's Syndrome in 2007. Drugs that receive Orphan Drug Designation obtain seven years of marketing exclusivity from the date of drug approval as well as tax credits for clinical trial costs, marketing application filing fee waivers and assistance from the FDA in the drug development process.
I hope everything is OK and the matters resolve themselves quickly and smoothly.
Perhaps, but your headline said "ObamaCare" is unconstitutional. That was not the ruling. What Congress decides to do with this is another, political matter.
What needs to be tossed out *if* the Supremes go the same way is stuff that has proven popular among both GOP & Dem voters.
On a political message board, the headline would merit a pass by me. On an investing message board, it's meaningfully inaccurate. We already have people bidding up health insurers today, which is exactly the wrong investment move given this decision.
Terrible headline, Dew.
(1) He specifically severed 1501 from the rest of the law. Only the mandate is unconstitutional.
(2) The decision from this judge was expected since he has equity in a conservative firm currently lobbying for repeal of this provision.
(3) The decision nuanced on the fact some idiot staffer substituted "penalty" for "tax" in the final bill format, likely to make it more "political palatable". This substitution was the basis for the judge's decision. If it had been a tax, it likely would have been constitutional (judge's background notwithstanding).
(4) The appeal will revolve around the argument whether it is a "tax" or simply a "penalty". That's General Welfare Clause and Commerce Clause, respectively.
I agree, but at least they are randomized. Mark Ratain, the arguable father of this trial design (or at least its biggest promoter) argues the enrichment is a byproduct but the important thing is tohave some randomization to help design the Phase III trials.
If you ever get a chance to chat with him about this design, it's worth the conversation. He's a great guy and one of the very few practicing clinicians (he's a hematologist) I've met who really understands statistics.
Who should we meet with?
Alan and I are setting up meetings with dev-stage biotech companies* during the JP Morgan conference in January. We're looking to initiate coverage on more dev stage companies.
1. Who do you think we should meet with?
2. Why do you think they are a good candidate for us to cover?
3. What questions would you like to have answered about them?
*We define "dev-stage biotech companies" as those whose market cap is primarily related to a drug NOT yet on the market. We prefer smaller companies, but have no market cap or trial stage restrictions.
To see what we already cover, go here:
http://www.biotechstockresearch.com/coverage.php
You can post here, PM me, or email us using the contact form on our web site.
Thanks,
David
The data seem impressive, but (a) I'm not a fan of the randomized discontinuation model, and (b) Talking to those more familiar with EXEL they strongly caution to believe the Phase III data when we see it and not get to excited.
If they can replicate those data in Phase III, it will be a big advance for men with PCa.
Their biggest challenge is getting the FDA to agree with a bone met measurement system that will result in a positive mention on the label for that benefit. Most PCA KOLs I speak with disagree on the right way to scan and adjudicate for bone mets so they'll be in uncharted territory if they try that route. This is one reason why cabazitaxel is the only drug shown to have a consistent effect on disease progression.
You mean robot armies don't already write them?
To me, "economic cost" is actual dollars. Selling a call and being called out on a running stock doesn't cost me actual dollars. It has a non-dollar cost I have to weigh for risk/reward, but getting called out subtracts no money from my account.
BTW, you're right in saying call sales hurt the company's valuation. Especially where there is growing short interest and heavy call writing, the market makers go short common to hedge the calls they buy.
About the only situation I can see where selling calls is going to lose you extra money is a very fast whipsaw move down then up. The down move sees your underlying common is taken out by margin call, stop loss, or manual sale. The up move sees the stock rising above your strike price + premium before you can buy the call back (or buy more common to cover). If there is a sector where that could happen, it is probably biotech because of the vol and propensity for trading halts on news. Come to think of it, this probably happened to people with the flash crash moments before the DNDN IMPACT data were released.
I also agree with you that people see covered calls as a hedge. They are absolutely wrong. Executed correctly, you can lose less money on a drop in the common. But they don't protect you from downside risk.
If one wants to be precise, and perhaps this is what you're getting at, you should actually size covered positions smaller than non-covered positions because you've limited upside reward and only partially reduced downside risk.
You mean opportunity cost, right, not economic cost?
roflmao...
DNDN
DNDN
Q3 results were one dose different than our estimates. (Q2 was 9 doses different). Q4 is lower, explained by management as a one-off holiday shutdown plus typical seasonality.
Nimotuzumab is not an Erbitux-like drug, of course, but an EGFR MAb with very different binding properties than Erbitux and Vectibix. It requires higher EGFR concentrations to be effective, but comes with lower side effects -- particularly rash. It remains to be seen whether YM can get this across the finish line. With the new acquisition and new targets, they seem to be falling into the "Ooh, shiny" trap they did previously.
They're going on my list along with Fidelity as funds to worry about if invested in a company I like.
BCa isn't my best area, but a couple of observations...
600mg bid is a LOT of drug. It will be interesting to see how this performs in broader patient populations.
They have a future trial design problem trying to figure out how to deal with T-DM1 in terms of choosing a path to approval. What have they guided for their next trial indication and design?
Agreed. Characterized by limited patient populations difficult to expand "off label" and clear benefit to risk.
If anyone comes up with a genetically-targeted obesity drug combined with a biomarker screen for the target, I'd be interested. Until then, it's smarter money to bet against all of them.
Yup. The SAE differential is the exciting part. It will be interesting to see which of the 3 arms in the pivotal is best.
The counter argument is ZGEN shareholders baked the expected milestone cash into the share price already, so no adjustment would be needed. That said, I'm not sure most ZGEN shareholders knew there was that much cash coming that quickly, so you might have a point.
If ZGEN shareholers knew that, plus the IL-21 results, plus the IFN-Lambda results (as BMY would have known) the stock price would have been higher so perhaps the buyout would have been higher. That would have made the percentages the same.
Sadly, it's academic now.
ZGEN - INF-lambda question
What percentage chance would you give interferon lambda in terms of receiving FDA approval in either (or both) HCV or HBV? We're not talking commercial success, just FDA approval.
Thanks.
(Dew, if you want to turn this into a survey, go ahead. I suggest 0/20/40/60/80/100% for numbers)
PYMX -- PMX-60056 is not the drug to get excited about. The drug to get excited about is PMX-30063. The trial just initiated provides the first look in target (non-healthy) patients so this is early, but the data will be very instructive as it is a head-to-head trial against an active control.