The debate over the extent to which doctors will embrace the Provenge prostate cancer vaccine shows no sign of abating. Last week, a survey found most insurers believe usage will remain flat over the next several months (see here). Now, another survey indicates most docs believe the survival benefit must be longer than shown in studies and financial concerns are also a factor.
Specifically, 68 percent of 101 oncologists and urologists queried believe, that in order to prescribe Provenge or a similar life-extending treatment, the survival benefit must be seven months or more. And more than 30 percent say a medication needs to add at least one year of life, according to Sermo, the web site where docs like to dish (see this). The median survival benefit offered by the Dendreon vaccine, which costs $93,000, is 4.1 months.
And although chemotherapy can also be very expensive, which is a point made repeatedly by those who believe Provenge is worth the cost, 86 percent of the physicians believe that Provenge and other life-extending meds should not run more than $60,000. In fact, 57 percent believe the price of such meds should be less than $30,000. And 19 percent cite $10,000.
Meanwhile, 68 percent say they do not believe they will be reimbursed if they have to purchase Provenge in advance of reimbursement. Earlier this month, Dendreon execs shocked investors by lowering sales forecasts and citing concerns that many docs, particularly those in smaller settings, were slow to adopt the vaccine over reimbursement (read this).
One doctor recently told us that he paid $31,000 for each infusion and Provenge requires a three-dose administration look here). Consequently, physicians fear that a large loss even if they fail to receive reimbursement for just one patient. Medicare has done a good job with reimbursement, but other insurers have not done the same, Philip Kantoff of the Dana Farber Cancer Institute, tells BioPharm Insight, a market research firm.
Reimbursement has been a heated issue. Some private payers have require special authorization for coverage. But as Dendreon boosters have noted, the coding from the Centers for Medicare & Medicaid Services that went into effect on July 1 should cover claims and payment, and they argue that reimbursement concerns may reflect worries over delayed payment more than outright rejection.
"There appear to be three barriers to adoption," Sermo ceo Daniel Palestrant tells us. "The first is provider education and familiarity with the treatment. The second one we’ve identified appears to be directly related to the novel nature of the treatment itself. And the third is billing...Do physicians understand this? My belief based on the data and experience with such matters is no. In general, there is a remarkable lack of understanding of the billing process and technologies among physicians."
In any event, the survey also yielded these findings: 41 percent of the specialists gree or strongly agree that the method used to administer Provenge and related training would deter them from adopting the vaccine or similar treatments. Meanwhile, 68 percent of the docs surveyed also say the co-pay is a major concern for their patients
Separately, the likelihood that an assay will be developed for Provenge appears uncertain, due to the entrance of newer prostate cancer drugs on the market such as Johnson & Johnson’s, which Zytiga costs about $5,000 a month for a median treatment cycle of eight months, according to BioPharm Insight, which canvassed several specialists (read here).
The Zytiga labeling requires a patient to be on chemotherapy, while Provenge is given a few weeks before or after chemotherapy, the reseach firms notes, adding that the two drugs can be used in combination. Provenge, by the way, must be given three to six months prior to Zytiga due to its impact on the immune system. Zytiga, meanwhile, is also being evaluated in a Phase III trial with patients who have yet to receive chemotherapy, with results likely next year, BioPharm notes.
21 Comments
Here we go again, Ed. "The survival benefit offered by the Dendreon vaccine, which costs $93,000, is 4.1 months."
This is an incorrect statement, and why you and others continue to state it, here and in other venues, when it's been corrected over and over again, defies logic.
What is so difficult to grasp about the data relative to Provenge's life extension benefit?
Please reviw this recent article:
http://seekingalpha.com/instablog/160858-theodore-cohen/211499-dendreon-and-fuzzy-journalism-wherein-lies-the-truth "...[t]here is no excuse for the continued dissemination of such misinformation. If a reporter is going to write about Provenge, then he or she owes it to their readers to present the truth. Now, this is not to say that they are not entitled to voice an opinion regarding the treatment, whatever that may be. Reporters are entitled to their own opinions, on Provenge or on any other drug or treatment. However, they are NOT entitled to their own facts.
"I am going to assume that reporters of all stripes who focused erroneously on a ‘four month’ life extension from Provenge have done so either because they ‘ripped’ the result from some other document or because they simply did not understand basic math, much less the statistics involved. So, perhaps those in the media (and others) who read this Blog might find the following discussion helpful when it comes to describing the benefits of Provenge:
"Instead of talking about a 4.1-month MEDIAN—not average—survival advantage demonstrated in the pivotal, 512-patient Phase 3 IMPACT study (which, admittedly, some people find difficult to understand because of the statistics involved), perhaps it would be better simply to talk about a 38% improvement in 3-year survival (31.7% survival rate at three years on the treatment arm compared to 23% for the control arm) and/or a 22.5% improvement in risk of dying. Put another way, the odds of a patient treated with Sipuleucel-T, which is the generic name for Provenge, surviving at 3 years was about one in three comparing to the odds of about one in five for an untreated patient. Think about it thisway: If you are a man 70 years old or older with metastatic prostate cancer, would you consider a treatment that would give you a chance of one in three to live 3 years longer instead of doing nothing and taking a chance of one in five or even less of living that long? I know what my answer would be!
"Results from the similarly designed Phase 3 Study D9901 in asymptomatic metastatic castration-resistant prostate cancer (CRPC) also demonstrated a survival advantage of similar clinical magnitude as the IMPACT study. This level of efficacy coupling with a mild side effect profile—mild flu-like symptoms—was remarkable when compared to the current standard of care, the chemotherapy Taxotere, which showed only a 2.5 months median improvement with possibly debilitating side effects."
"Furthermore, it should be noted that in contrast to other trials, including the ones for Taxotere, patients on the control arms of the Provenge trials were allowed to cross over and take a weaker form of Provenge after disease progression. This could exaggerate the survival rate and the median survival time of patients on the control arms. That is, the 4.1 months median difference or the 22.5% improvement in the risk of dying, could be much better if the control arm of the IMPACT trial was using a pure placebo. For example, in a recent study presented at the ASCO 2011 Symposium (http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=102&abstractID=82559), it was found that the median survival times were respectively 20.0 months and 9.8 months for patients who crossed over to the weaker form of Provenge and patients who did not receive any form of Provenge. Patients who crossed over also had 48% less risk of dying than those who did not. These data are substantiated by material submitted to the FDA by Dendreon, and are available in the archival literature."
Ed, if we are going to have a debate, do surveys, discuss Provenge in any context, let's at least get the facts correct.
Please?
Thank you.
^^^^^ what a shill!
"Disclosure: I am long DNDN and will not alter my position within 72 hours of the time of publication of this article."
Hi MyPharmalotID,
Thanks for the note and the explanations, which are much appreciated. While I did not use the word 'average' to describe the survival benefit, I have inserted the word 'median' so that the full extent can be appreciated.
As to the other trial results, I understand your points. As with the last survey that queried insurers and was undertaken by an outside firm, I chose to post this item simply because it provides a snapshot.
And so if the snapshots illustrate that, say, insurers or physicians, are ill-informed or do not understand some of the intricacies, then that is worth knowing and, as you make clear, also worth discussing and clarifying.
In any event, thanks for writing in. Regards, ed
Thanks, Ed. And thanks to Warren for his continued support. If he can do for DNDN what he did for BOA, we'll be just fine. (;>)
The information for insurers and physicians is readily available on both the Dendreon and CMS Web sites. See, for example:
http://www.provenge.com/
http://www.nccn.org/images/emails/ebulletin/11-07-25/NCD_Announcement.pdf
Recent discussions with Dr. Leonard Liang, a California urologist and surgeon who has several patients on Provenge and who you interviewed recently, indicate he is having no problems with reimbursement. In fact,there are indications reimbursements have sped up now that CMS published the Q-code on August 3, 2011. (The final J-code will be published January 1, 2012.)
Full disclosure: I am long DNDN. I know this will make Warren uncomfortable and send him into the market for more shares within 72 hours, but such is life in the fast lane.
MyPharmalotID, the reason the "4.1 years" survival advantage that Dendreon shareholders find so troubling is found everywhere is because that is the data found in the FDA approved Prescribing Information for the drug.
Regulatory authorities and cancer researchers in general prefer to use the median value because it is less likely to be skewed by a handful of long term survivors who may have entered the study with less severe disease or other favorable non-treatment related prognostic factors.
The oft-quoted greater proportion of Provenge-treated patients alive at 3 years gives the impression that there are a great many more long-term survivors than in the placebo group. But if you look at the survival curves in the Prescribing Information, the number of Provenge treated patients alive at 40 months is the same as the number of placebo-treated patients alive at 36 months.
Four months median survival difference actually sums the trial results fairly well.
john - just to be sure:
When you said the following above - you meant MONTHS and not years? As you did at the end?
MyPharmalotID, the reason the “4.1 years” survival advantage that Dendreon shareholders find so troubling ...
Four months median survival difference actually sums the trial results fairly well.
+++++++++++++ Or are my observations more confused than usual?
John, I beg to differ. It's far more complex. Here are the data for the Kaplan-Meier Survival Rate Estimates in the Pivotal Trial (Provenge, n=341; Control, n=123):
Percentage of patients alive:
First year: Provenge: 81.1 (n=274) Control: 72.4 (n=123) Percentage increase in PROVENGE Group vs. Control Group: 12.0%
Second year: Provenge: 52.1 (n=129) Control: 41.2 (n=55) Percentage increase in PROVENGE Group vs. Control Group: 26.5%
Third year: Provenge: 31.7 (n=49) Control: 23 (n=19) Percentage increase in PROVENGE Group vs. Control Group: 37.8%
Fourth year: Provenge: 20.5 (n=14) Control: 16.0 (n=14) Percentage increase in PROVENGE Group vs. Control Group: 28.1%
Given my druthers, I'd choose Provenge in a heartbeat.And frankly, given this and other venues where the subject of life extension has come up, there is no excuse for not discussing the matter rigorously. This is, after all, a matter of life and death.
I'm amazed at the stupidity of people who say a drug should cost 10k or 30k or whatever. Does anyone care to know what it cost to bring not only Provenge but any cancer therapy to market?
I'm disgusted by the medias portrayal of Dendreon and Provenge. If Pfizer had gotten approval of Provenge this article would never have been written.
MyPharmalotID, look at the percentage alive on Provenge at each of those time points, and compare it to the number alive on placebo 4 months earlier. Its really not that complicated.
You can express the same data in a lot of different ways, but I think your preferred method gives people the impression that there is a much larger effect than actually exists. The 4 month median survival difference creates a large percentage difference at specific time points only because all of these patients are dying off so rapidly.
When you say xx% are still alive at 3 years, lots of people tend to assume that most of these patients are long term survivors who will still be around 2 years later. That's clearly not the case from the survival curves.
Observer, it should read "months", thanks.
John, at some point the curves converge and they're all dead. But as they say in tennis, when all is said and done, Advantage: Provenge. And if we're going to talk about the advantage, my only point is that we be correct in how we speak about it. That's simply my point.
All these "medical" experts are spreading false negative rumors about Provenge. The truth is Provenge has demonstrated the best overall survival for any cancer medication in recent history. If you want to understand what 4.1 months MEDIAN benefit means then read this document. Patients, your best bet of survival for prostate cancer is with Provenge. Read this for proof.
https://docs.google.com/document/d/1Go9VLVZ0-p4F0btWXIb_Ud2A1079r9uigwyuu627ROQ/edit?hl=en_US
Please read this: http://goo.gl/4rt4i to understand what 4.1 median survival advantage means and why Provenge has shown the best overall survival of any cancer medication in recent history
I agree with Steve B above.
I too am disgusted with the portrayal of Provenge and Dendreon and agree that if this was a product from a major drug company none of this would be happening.
I challenge Ed or anyone else to go on the internet and round up stories about a new cancer treatment by one of the major companies that in any way resembles the massive attacks that have been waged against Dendreon in its attempt to bring this vaccine to market over the past 4 or 5 years.
Apparently I must be the only journalist in the US who has investigated the joining together of the powerful factions within the cancer research-treatment industry thoroughly enough to understand exactly what is going on here.
But to be clear, my investigation was not done to benefit Dendreon, it was driven by my sympathy and compassion for the dying prostrate cancer victims caught in the middle of the warring profiteers.
Therefore, I find it rather strange that the only voices that never seem to warrant inclusion in the endless string of stories about Provenge, on this site and many others, are those of the prostrate cancer victims.
An anticancer prodcut does not show any sign against prostate cancer but prolong survival? What A joke in medicine history!
Provenge represents a biological religion to some. That is it! It may harm patients. It is unusually high in the PSA era that about 20-30% of patients with early stsge metastatic CRPC who died within 12 months. =cCome on, stop cheating patients and stop contaminating medical science.
Most physicians who have a high sense of professionalism most likely will not use this product whose effectiveness is highly questionable. A few so-called experts who repeatedly express their support of the product are less scientifically competent to understand the complexity of the problems. They should release how much research fund or other financial gains they got from the company.
You're absolutely right Evelyn. In my own investigation, I spent 6 hours examining various industry-focused and general news websites. Except for the relentless and unfair criticism of Dendreon, I was not able to find a single example of any of the following:
1) Drug companies being criticized for the price of their products
2) The efficacy and cost effectiveness of FDA approved products being questioned
3) The FDA rejecting NDAs for drugs that missed their primary endpoint in both pivotal trials
4) Companies seeing their share price drop after missing their earnings estimates.
Clearly there is something going on here.
"Most physicians who have a high sense of professionalism most likely will not use this product whose effectiveness is highly questionable."
Wow. That's a pretty strong statement, Pseudo Science. This one is even more interesting:
"A few so-called experts who repeatedly express their support of the product are less scientifically competent to understand the complexity of the problems."
The mind reels.
2 questions for anyone who may know.
How much money does a doctor make when treating a prostrate cancer patient with Provenge?
How much money does a doctor make when treating a prostrate cancer patient with chemotherapy?
It is PROSTATE.....
Josh, maybe the sophmoric nature of many of the posts on these boards renders Evelyn prostrate as it does I. Cut us a break.
Evelyn, I'm afraid getting a physician to reveal how much money he makes off a procedure is a futile exercise, but I will tell you that many of the oncologists in my hospital parking lot drive a late model German automobile beginning with the letter "B" and ending with "W". Thus I would say that overall they are doing pretty well.
But coming from a "journalist", I expect more.....