Much Ado About Medarex

According to their website, Discovery’s Edge is the Mayo Clinic’s online research magazine that is designed to communicate the story of scientists and researchers who are bringing treatments and improved care to patients and also reports on “works–in–progress.” Through this publication, Mayo investigators studying immunotherapy for aggressive prostate cancer reported over the past weekend that a combination therapy dramatically reduced tumor size to make surgery possible for two patients whose prostate cancer had been previously considered inoperable. While preliminary, Mayo reported that the results were significant enough for future research.

As noted in our recent articles, investors have been “irrationally exuberant” towards biotechnology companies working in the field of prostate cancer – even those in the early stages of development. In keeping with this theme, the Mayo news drove shares of Medarex, Inc. (MEDX) up more than 20% on Monday morning with significant volume, as the immunotherapy referenced in the investigator-sponsored study involved the company’s Ipilimumab product candidate. Ipilimumab is a fully human antibody that binds to CTLA-4, a molecule on T-cells that plays a critical role in regulating natural immune responses.

Enough has been written about the fact that the positive results were demonstrated in a mere two prostate cancer patients and the lack of information provided in the Discovery’s Edge publication (see Associated Press article), so I won’t belabor the point.

It is interesting to note, however, that Medarex included a summary of the Mayo report from two patients under the news section of the company’s website, yet the company didn’t report Phase 2 study results with Ipilimumab in aggressive prostate cancer that were reported by researchers at Memorial Sloan-Kettering Cancer Center [MSKCC] during the Annual Meeting of the American Society of Clinical Oncology [ASCO] held May 29-June 2, 2009. See abstract #5138 titled “Initial phase II experience of Ipilimumab [IPI] alone and in combination with radiotherapy [XRT] in patients with metastatic castration-resistant prostate cancer [mCRPC].”

In the MSKCC study reported at ASCO, 45 patients with mCRPC received Ipilimumab in 3 groups:

1. Ipilimumab alone, n=16
2. Ipilimumab + XRT, n=15, in chemotherapy naïve
3. Ipilimumab + XRT, n=14, in chemotherapy experienced patients

In the study, PSA declines ≥ 50% were seen in 10 of 45 (22%) patients. Only one patient from Group 1 (Ipilimumab alone) demonstrated a PSA ≤ 0.05 ng/ml and complete resolution of bone, nodal and prostate lesions that continued for 54+ and 84+ weeks, respectively.

While Medarex issued a press release on May 31, 2009 summarizing the results from three Phase 2 studies of Ipilimumab in metastatic melanoma at ASCO, there was no such communication regarding the Phase 2 results from MSKCC in prostate cancer that certainly don’t live up to the hype generated by the results from the Mayo Clinic report.

Disclosure: No positions

Comments

[fran grady:]

is this a scam??

Jun 25 08:43 AM

[kyoto27:]

Michael, there was much hyping of MEDX a few days ago by Prohost Biotechnology--which I assume is a competitor the bio newsletter space. The report read like a paid 'pr' funded by some desperate hedge funds.
Question: Who are the real owners of Prohost Biotechnology?

Jun 25 10:47 AM

[in4thelonghaul:]

This is a tough one simply because of the odd and unorthodox nature regarding the manner this stunningly positive "news" came public and of course the small amount of patients involved - apparently 3 patients now, not just the first 2 mentioned originally.

Astute biotech watchers will remember that some very serious side-effects have been linked with use of ipilimumab in past trials.

Obviously, if Mayo is still attempting to enroll patients, questions can legitimately be raised as to motivation for the timing, wording and manner of the 'news' which found its way to the public...maybe nothing there, time will tell.

It will all be moot if serious side-effects have been avoided and further patients are revealed to have achieved similarly stunning results, results where cancer has apparently vanished. I find it unlikely that the story is anything less than has been portrayed, simply because Mayo's reputation is on the line here.

I think everyone's hope is for these first and apparently stunning results to be repeated in other patients in the treatment arm.

Biotech shareholders of companies with competing treatments have expressed some justified skepticism. MEDX shareholders can expect to achieve considerable sh/pr appreciation in the coming years if these results are as indicated and widespread, even more so if ipilimumab is successful with melanoma.

Considering the potential, it seems shares around $8.00 present a decent risk/reward. If the melanoma trial disappoints, MEDX shares could easily retest their recent lows and remain depressed for considerable time, especially if serious side effects are again linked with use if ipilimumab. OTOH, if all goes well, MEDX has a potential blockbuster on their hands and shares could easily skyrocket towards $30.00 in quick order.

Jun 25 11:08 AM

[Michael Becker:]

Upon a brief review of their website, there are absolutely no individuals or biographies listed. Hard to imagine that anyone would subscribe to a newsletter without background about the author(s), but that is not my concern. Needless to say, I am at a loss to answer your question as to who is behind this organization.


On Jun 25 10:47 AM kyoto27 wrote:

> Michael, there was much hyping of MEDX a few days ago by Prohost
> Biotechnology--which I assume is a competitor the bio newsletter
> space. The report read like a paid 'pr' funded by some desperate
> hedge funds.
> Question: Who are the real owners of Prohost Biotechnology?

Jun 25 02:20 PM

[Michael Becker:]

The challenge here is that androgen ablation is already known to decrease the size of the prostate by approximately 20-50% in patients with locally advanced disease and reports indicate the disappearance of disease in up to 5% of patients treated (whether this impacts overall survival is another topic...). Based on the information provided, there is just no way to determine if the remarkable responses in a few patients would have occured with androgen ablation alone (eg, without the addition of experimental ipilimumab) as documented in the medical literature and pointed out by Derek Raghavan, MD, PhD, from the Cleveland Clinic's Taussig Cancer Institute.



On Jun 25 11:08 AM in4thelonghaul wrote:

> This is a tough one simply because of the odd and unorthodox nature
> regarding the manner this stunningly positive "news" came public
> and of course the small amount of patients involved - apparently
> 3 patients now, not just the first 2 mentioned originally.
>
> Astute biotech watchers will remember that some very serious side-effects
> have been linked with use of ipilimumab in past trials.
>
> Obviously, if Mayo is still attempting to enroll patients, questions
> can legitimately be raised as to motivation for the timing, wording
> and manner of the 'news' which found its way to the public...maybe
> nothing there, time will tell.
>
> It will all be moot if serious side-effects have been avoided and
> further patients are revealed to have achieved similarly stunning
> results, results where cancer has apparently vanished. I find it
> unlikely that the story is anything less than has been portrayed,
> simply because Mayo's reputation is on the line here.
>
> I think everyone's hope is for these first and apparently stunning
> results to be repeated in other patients in the treatment arm. <br/>
>
> Biotech shareholders of companies with competing treatments have
> expressed some justified skepticism. MEDX shareholders can expect
> to achieve considerable sh/pr appreciation in the coming years if
> these results are as indicated and widespread, even more so if ipilimumab
> is successful with melanoma.
>
> Considering the potential, it seems shares around $8.00 present a
> decent risk/reward. If the melanoma trial disappoints, MEDX shares
> could easily retest their recent lows and remain depressed for considerable
> time, especially if serious side effects are again linked with use
> if ipilimumab. OTOH, if all goes well, MEDX has a potential blockbuster
> on their hands and shares could easily skyrocket towards $30.00 in
> quick order.

Jun 25 04:30 PM

[kenny b:]

<<The drug was intended to put patients into a "holding pattern," according to Robert Nellis, a Mayo Clinic spokesman said in a telephone interview to Bloomberg on Monday. "The effect they were hoping for was a stabilizing effect, to buy these people more time," Nellis said. "They put them on this not seeking this outcome...The third patient has been cancer free for a week and a half."

Was it the surgery and the cancer-free status of this third patient 10 days ago that prompted the press release? Now that we have a third patient cancer-free, are these "cures" blossoming into something more than just being anecdotal? Where does "anecdotal' become more than just "anecdotal?" Shouldn't trial protocol be broken to include all patients with evidence of striking down-staging of their disease as eligible for surgery, instead of being contained in a holding pattern?

According to James Allison, et.al., androgen ablation promotes infiltration of antigen-specific T-cells into normal and cancerous prostate tissue, essentially turning the prostate into an "in-situ vaccine." He postulates ctla-4 blockade will ultimately potentiate this T-cell mediated anti-tumor response, initiated by A.A. In my opinion we are now seeing evidence supporting his postulate and that these early results are something more than just "anecdotal." >> Michael, Whats your tipping point 4 patients 5 patients 10 patients. The IPI arm is only 54. OR does AA after all these years of very rare action suddenly become a miracle cure? kenny B.

Jun 25 06:15 PM

[Michael Becker:]

Kenny B - First, having lost a family member to prostate cancer, I am as hopeful as the next guy for innovative treatments. However, as Dr. Raghavan from the Cleveland Clinic stated (www.webmd.com/prostate...), the fact remains that until more details of the results and trial are published, there is just no way to assess the impact of ipilimumab on outcomes. However, if the ipilimumab arm is 54 patients as you reference, and 5% of patients on androgen ablation alone can experience resolution of their disease, then simple math dictates that 2.7 patients could reasonably be expected to have such an outcome. Thus, I don't see the rationale for enthusiasm over 2-3 patients at this point - as that is what would be expected. But again, we can only assess ipilimumab in this setting when the study is completed and the results are vetted in an appropriate scientific venue years from now.


On Jun 25 06:15 PM kenny b wrote:

> <<The drug was intended to put patients into a "holding pattern,"
> according to Robert Nellis, a Mayo Clinic spokesman said in a telephone
> interview to Bloomberg on Monday. "The effect they were hoping for
> was a stabilizing effect, to buy these people more time," Nellis
> said. "They put them on this not seeking this outcome...The third
> patient has been cancer free for a week and a half."
>
> Was it the surgery and the cancer-free status of this third patient
> 10 days ago that prompted the press release? Now that we have a third
> patient cancer-free, are these "cures" blossoming into something
> more than just being anecdotal? Where does "anecdotal' become more
> than just "anecdotal?" Shouldn't trial protocol be broken to include
> all patients with evidence of striking down-staging of their disease
> as eligible for surgery, instead of being contained in a holding
> pattern?
>
> According to James Allison, et.al., androgen ablation promotes infiltration
> of antigen-specific T-cells into normal and cancerous prostate tissue,
> essentially turning the prostate into an "in-situ vaccine." He postulates
> ctla-4 blockade will ultimately potentiate this T-cell mediated anti-tumor
> response, initiated by A.A. In my opinion we are now seeing evidence
> supporting his postulate and that these early results are something
> more than just "anecdotal." >> Michael, Whats your tipping point
> 4 patients 5 patients 10 patients. The IPI arm is only 54. OR does
> AA after all these years of very rare action suddenly become a miracle
> cure? kenny B.

Jun 25 06:54 PM

[kenny b:]

On Monday, Eugene Kwon, a Mayo Clinic urologist and leader of the clinical trial, told Dow Jones Newswires a third patient has recently been affirmed to be cancer free after undergoing the same treatment. The operation to remove that patient's tumor occurred 10 days ago, Kwon said, adding that there may be similar results to come among another 15 to 20 patients in the trial. Michael Dr. Kwon"s statement regarding ( another 15 to 20 patients that may have similar outcomes is the rational for enthusiasm) . You only need a few more of these patients to far exceed any result that could be explained in any other way.

Jun 25 09:54 PM

[Michael Becker:]

Again, we can only assess ipilimumab in this setting when the study is completed and the results are vetted in an appropriate scientific venue years from now, as I doubt the Mayo Clinic will continue putting out patient-by-patient results.

Jun 26 08:29 AM

[kenny b:]

www.cbsnews.com/storie... Michael you should watch this video

Jun 26 08:30 AM

[Michael Becker:]

Kenny B - Thanks for the link, but I've been an industry executive for quite some time, so I don't need to see fancy computer animation to understand how ipilimumab works. Interesting to note, however, the following quote from the link you provided: "The study has been broken," CBS News medical correspondent Dr. Jon LaPook reported. "but the Mayo Clinic is starting over in the fall with a new study. And if that's successful, the study will go to its next phase."

Further, many people in our industry remember EntreMed (ENMD), a company working in the area of anti-angiogenesis, which gained worldwide attention back in 1998. They were on the front page of the New York Times reporting on the fact that one of their drug candidates had stopped tumor growth in mice and that this might be the long heralded cure for cancer. The news was picked up around the world and the stock price traded above $100 a share around that time. It recently closed at about 50 cents.

No fancy video animation changes the fact that the results with ipilimumab are very early we can only assess the product when studies are completed and the results are vetted in an appropriate scientific venue, which based on the information from the link you provided will be years from now. My sincere hope at that time is that the product offers meaningful benefit to men fighting this disease.


On Jun 26 08:30 AM kenny b wrote:

> www.cbsnews.com/storie...
> Michael you should watch this video

Jun 26 09:38 AM