Prostate Cancer Doctor Receives Death Threat Over Provenge
Oncologist Dr. Howard I. Scher has received a death threat for opposing immediate FDA approval of Dendreon’s Provenge therapeutic vaccine for prostate cancer. Another oncologist who opposes approval of Provenge without completion of an ongoing clinical trial, Dr. Maha Hussain, has received unspecified threats.
The background to these threats goes back to March 29, when both doctors voted No on an Advisory Committee appointed to decide whether Provenge has substantial efficacy as an immunotherapy for late-stage, androgen independent prostate cancer (AIPC). Twom other panel members voted No while 13 voted Yes. Rather than accept the majority decision, Scher and Hussain wrote letters to the FDA reiterating their objections to immediate approval. Their letters were obtained and published by The Cancer Letter, which went on to publish a third letter to the FDA opposing Provenge approval, from biostatistician Thomas Fleming Ph.D. The Cancer Letter also received a letter in favor of Provenge approval, signed by doctors who are Dendreon investors and a by a researcher at Sanofi-Aventis. Scher’s, Hussain’s and Fleming’s letters are reprinted on this website. These letters have been subjected to heated analysis investors’ message boards.
During and after the Committee meeting, Dr. Hussain expressed willingness to support compassionate use or expanded access to Provenge whilst the trial went on. Dendreon CEO Mitch Gold said last week, “We have given thought to that and we believe that the best way to bring Provenge to market and to help patients is through the approval regulatory process we are pursuing currently. The company doesn’t have the resources to participate in an expanded access or compassionate use [program].”
New York Times health writer Andrew Pollack, in a report from Chicago today, raised the possibility that the death threat and other threats came from prostate cancer patients. Pollack offered no evidence for this:
Two prominent prostate cancer experts have been threatened for opposing approval of a controversial new drug and are being protected by bodyguards as they attend the nation´s largest cancer conference here.
The experts, Dr. Howard Scher of Memorial Sloan-Kettering Cancer Center and Dr. Maha Hussain of the University of Michigan, received email and other threats, according to spokeswomen for Sloan-Kettering and for the cancer conference.
It is not known who sent the threats. However, it is clear that the doctors´ public stance against the drug, Provenge, has inflamed the passions of some men with prostate cancer and patient advocates, who say the drug would offer hope to desperate patients with few or no alternatives.
Many investors also have made big bets on the stock of the drug’s developer, Dendreon, a Seattle biotechnology company, whose stock has fluctuated wildly based on prospects for the drug. Some investors stood to profit if the drug was approved and others if it was rejected.
The F.D.A. said in May that it would not approve Provenge without more evidence that it was safe and effective.
Patients with incurable diseases often advocate for approval of new drugs even if the data supporting them are not perfect. But threats to those who take an opposing position on a drug appear to take such advocacy to a new level. That could discourage rational discussion of drugs or deter experts from serving on advisory committees to the Food and Drug Administration, where Drs. Scher and Hussain first publicly voiced their opinions.
“Intimidation or harassment is going to make qualified people think twice about serving in national positions,” Dr. Hussain said in a brief conversation here at the annual meeting of the American Society of Clinical Oncology. She said she would continue for now to serve on F.D.A. advisory panels.
Dr. Scher also was reluctant to comment, saying, “This is a situation I’ve never been in before.”
But he seemed distressed that other doctors were not publicly rallying to his support. “There´s no one else standing up and saying this is ridiculous,” he said.
When he gave a talk at the conference on Sunday, Dr. Scher was accompanied by three men wearing suits and earphones but without mandatory conference name badges.
A spokeswoman for the oncology association said it had been working with the two doctors and was increasing security at the conference
Christine Hickey, a spokeswoman for Sloan-Kettering, said Dr. Scher had received e-mails and phone calls, including one e-mail entitled “your murder.” A copy of his biographical page on the Sloan-Kettering website was defaced.
Provenge has become the latest focal point of a long-running and sometimes bitter debate about the degree of evidence needed for approval of drugs for life-threatening diseases.
Cancer Experts Threatened After Opposing Drug (login-in required; the version now online is much shorter than the above, and Pollack’s byline has been removed).
We first heard of a death threat against Dr. Scher from a reliable source in late April after his letter to the FDA. No indication suggested that this threat came from any patient or advocacy group. All along, invective and “rants” against Scher and Hussain have been high on investor message boards, with no such feelings expressed on a leading prostate cancer mailing, PPML at acor.org.
By last week, investors were circulating Dr. Scher’s email address and phone number, urging that his office be bombarded with FAXes, and analysing an EDGAR record of his investments. Based on Scher and Hussain’s declarations to the FDA and receipt of COI waivers, Dendreon investors who allege that the two oncologists are motivated by financial interests seems to see nothing wrong with the fact that one of the clinical investigators for Provenge, Dr. Paul Schellhammer, who edited a report on the Phase III trials for publication, benefits financially from the company.
Yesterday a group of Dendreon investors, including some who are medics and some who are prostate cancer patients, staged a protest outside the Chicago meeting, ASCO, where Scher needed bodyguards inside. The protesters dressed in blue jeans and blue T-shirts, copy-catting a style pre-arranged by prostate cancer patients and advocates for the Raise a Voice Assembly and assembly in Washington DC (June 4). Jim Kiefert of US Too! dropped by at the Chicago event. The protesters received media coverage, but had not applied for a license to assemble and leaflet. After about an hour police asked them to move on.
Folks, this is not grassroots cancer patient activity, it’s astroturf advocacy — or naked grassroots investor activity. Ironically, some investors have whined that prostate cancer patients are not helping THEM on behalf of Dendreon.
To follow their opinions visit: investorvillage.com
First, no threat to anyone because they expressed their views should be tolerated! Such violators deserve to be prosecuted.
That said, there are legitimate questions to ask about Dr. Scher’s position to request the FDA to delay the approval of Provenge. There were numerous inaccuracies in Dr. Scher’s letter to the FDA that was leaked to the Cancer Letters. However, I would like to draw your attention to the below excerpt of Dr. Scher’s comparison of the trial data between Provenge (Sipuleucel-T) and Asentar (DN-101) and a question that he asked to the FDA on the same drug.
“the pre-specified survival analysis showed a difference for docetaxel plus DN-101 vs. docetaxel plus placebo: median not reached but estimated to be 24.5 months vs. 16.4 months respectively with a hazard ratio for death of 0.67 (p=0.04)(JCO 25:669- 74, 2007)… Why do the Sipuleucel-T results establish efficacy, while the DN-101 results do not?”
A few comments on the above quotes:
1. First, Dr. Scher made an invalid comparison of the p-value=.04 of DN-101 against the Provenge p-value=.01. The p=.04 of DN-101 was computed by a Cox Regression while the p=.01 of Provenge was computed by a log-rank analysis. It is accepted in biostatistics that the log-rank procedure, being non-parametric, is more reliable than a Cox Regression. Traditionally, the FDA has only considered log-rank analysis in approving new drugs while Cox Regression was done only as sensitivity analysis to ensure that the data do not contain any untoward imbalances aiding the treatment arm in a blinded trial. In fact, known DN-101 trial data showed that the log-rank p-value of DN-101 was actually .07, missing the conventionally accepted significance level at .05. That statistical miss was improved only by the Cox Regression to .04, closely meeting significance. By contrast, if the Cox Regression was done on the Provenge data, its already highly statistically significant log-rank p-value of .01 would improve to .002, nearing the area where statisticians would call statistically persuasive. That is, there was little question that the Provenge data were superior to the DN-101 data.
2. As such, the above question that Dr. Scher raised in a letter to the FDA was not valid even if it was to be interpreted only as being rhetorical. In fact, Novacea has not even submitted an NDA (New Drug Application) to market DN-101 since its pivotal trial has not completed. Thus, the FDA could not have said anything about whether or not its results have established substantial evidence of efficacy. However, it is ironically clear that Dr. Scher or whoever advised him to write his letter apparently had the marketing issue of DN-101 in mind in that question.
3. It is worth noting now that Dr. Scher is the lead investigator of an on-going DN-101 trial that will provide the data leading to an NDA to market the drug. As such an expert deeply involved in the development of DN-101, his error above in comparing statistical data is distressing at best and disingenuous at worst. The latter, if true, shows that he or his advisor in writing the letter had some ulterior motives in downplaying the excellent Provenge data.
4. Lastly, Provenge, if approved, would have been the front-line therapy for AIPC (Androgen Independent Prostate Cancer). That is, it would be used before the combination of DN-101 and Taxotere. Now that its approval is delayed, if the DN-101 trial is successful next year, DN-101+Taxotere would become the standard of care in a multi billion dollar market. It is interesting that immediately after Dr Scher and colleagues successfully blocked the approval of Provenge, Novacea and Schering-Plough inked a half-billion dollar deal and announced that they will further develop DN-101 into the even larger market of ADPC, Androgen Dependent Prostate Cancer.
Comment by ocyan — June 5, 2007 @ 10:51 amI don’t know if Howard Scher actually received death threats. He is not an honest person and lied about his Conflict of Interests. He is the lead researcher of a competing drug, Novacea’s Asentar, which recently received multi-million dollars from a partnership with Schering-Plough. He didn’t disclose this in his Conflict Of Interests waiver for Advisory Committee meeting of Provenge. That being said, it is OK to vote NO and voice concerns at the AC meeting. However, didn’t he and Maha Hussain go too far by writing letters and “leak” the letters to the Cancer Letter?
I heard that some Hedge funds made millions of dollars shorting Dendreon stock before FDA’s decision to delay the approval of Provenge on May 9. If Maha Hussain is so keen to the idea of early access program, why doesn’t she sponsor such a program with the help from those Hedge Funds.
I checked the web site you mentioned. I don’t agree with some of the conspiracy theories on the message board. However, I do agree with them that it is not right for the FDA to delay the approval of the drug after the recommendation of approval by the AC.
Comment by HH — June 5, 2007 @ 8:02 amAs an attendee of the rally conducted in Chicago, it seems a few clarifications are in order.
A permit is not needed to peaceably assemble in a public forum and location, provided certain guidelines are followed with respect to not blocking pedestrian traffic, etc. The right to peaceably assemble is a right all Americans have under the First Amendment of the Constitution. Again, there are guidelines that must be adhered to with respect to an assembly in a public location, but no permit is required.
It appears that the “bridge” inside McCormick Place (also known as the “skybridge” which connects the McCormick buildings) where the main rally occurred was not a public access facility as the organizers believed; it is owned by McCormick Place and as such, not a public venue as was anticipated. It should be noted that the rally was allowed to carry on peaceably outside, in Burnham Park, which is a public park, no permit required.
In reference to your quote, “Yesterday a group of Dendreon investors, including some who are medics and some who are prostate cancer patients, staged a protest outside the Chicago meeting, ASCO, where Scher needed bodyguards inside.” - I find the wording of this statement and the inference contained therein to be grossly misleading in the extreme. The Chicago rally attendees are on record as not supporting nor condoning any violent or harmful actions contained within any communiques Drs. Scher or Hussain might’ve received.
And lastly - unless the threatening communiques allegedly sent to Drs. Scher or Hussain are made public, there is no way of knowing with any certainty what kind of individual made them. Your theory that it was an investor is simply that - a theory. While it’s entirely possible these threats were made by an investor, they could’ve also been made by a desperate prostate cancer patient, or a member of that loved one’s family. Not any of us know the identity of this person or persons, and to propogate an assertion one way or another is mere speculation at best.
Peace,
Comment by Artavia — June 5, 2007 @ 12:30 amArtavia
First of all, no reasonable person condones “threats” to Dr Scher and Hussain. But please do not trivialize the passion these patient advocates have towards Provenge. Put yourself into their shoes. If your loved one had incurable prostate cancer and had 18 months to live and refused Taxotere(only FDA approved drug for this setting) which wouldnt be surprising since half of patients decline chemotherapy, how would you feel if two very influential oncologists went above and beyond the call of duty to make sure Provenge didnt get FDA approved(ie-The Cancer Letter leak).
If I were talking about a NSAID or etc where there are many choices already out there, then the efficacy and safety data should be met with vigor. But when you know Provenge is safe(17-0 vote at AC meeting) then what do these patients have to lose???. Dr Scher and Hussain seem to take a patronizing approach implying that the public is too uninformed to make a reasonable choice. Is this really true?.
So lets talk about the efficacy data in which the AC voted 13-4 that Provenge showed “substantial evidence” for efficacy. Although Dr Scher implied that when the efficacy question was changed during the middle of the AC meeting to “substantial efficacy”, that this was done to “help” Dendreon, this is clearly wrong. This new definition is clearly stated under FDA guidelines.
So lets talked about the efficacy data. Time to Progression(TTP) was the primary endpoint and it has been stated over and over again it was missed. Was it really missed when it came in at p=0.052???(p=0.05 is the accepted p value for being significant). Any reasonable person would accept this as being positive. Because Dr Scher and Hussain wouldnt accept the primary endpoint miss at p=0.052, they then wouldnt accept the overall survival benefit(4.5 month benefit, p=0.01, highly significant). Well, while short sighted purists might not accept the survival benefit seen but any reasonable person would accept that the survival benefit seen was real. Even the FDA’s own statistician at the AC meeting said the chances that the survival benefit seen in 9901/2 studies was due to a statistical anomoly was 1/40!!!. So how can Dr Scher and Hussain continue to say that the positive Provenge survival data “could be due to a statistical” fluke. Well, I think the person who will die within 18 months should be allowed to make the choice that they could be taking a placebo-like sugar pill 1/40 times. To tell a dying man that he cannot have a drug that could potentially extend his life significantly due this 1/40 chance that this drug really doesnt work is so ludicrous its beyond words. If you dont believe me, I would like you to tell these patients and their families that you dont think they should have access to Provenge and then explain the data and the significance of the p values to them. I bet you cant or wont. This ultimately cuts to the essence of this entire debate. This isnt about Provenge, this is about patient rights and choice. Do you choose “patients over process” or “process over patients”??? Its really that simple of you think about it.
While Dr Scher and Hussain will argue all day long that the “rules of their game”(ie-the typical FDA approval process) dictates that no drug that fails its primary endpoint should ever be approved, by playing this “game”, they have lost sight of whats important. Patients dont care whether there is a 95% chance the survival data is real or a 75% chance cause there are no alternatives other than death! Why cant Dr Scher and Hussain understand this???.
Lastly, please be careful about what you say on here cause “off the cuff” remarks noting that this is a astroturf investor movement rather than true grass roots movement is an insult to the prostate cancer community that is either suffering from prostate cancer or have lost a loved one to this horrendous disease. You may see this as a battle of long and short investors but for many, its life or death and you have no right to trivialize this situation.
I think many people will learn from the Provenge saga. It might take many years to fully appreciate what is going on here but they will one day. Dr Scher and Hussain will soon realize that this isnt a “FDA approval process” game. They will realize its much more profound than that. They are probably shocked that the public sentiment is so strong against them but they started a tidal wave that they cannot understand or control. The patients and their families are demanding a choice and they wont take no for an answer anymore. If the FDA wants to make this a political issue, well, I think they are going to get their wish. The Abigail Alliance and their lawsuit will bring even more light to this outdated and broken down system we call the FDA.
Comment by imolas54 — June 4, 2007 @ 11:18 pm