Re: updated survival data.
This was ASCO 2008 ANNUAL MEETING CC MEDX:
HOWARD PIEN, PRESIDENT AND CEO, MEDAREX, INC.: Good morning, and welcome to Chicago to the Medarex Webcast on the ASCO Data of Ipilimumab. Before we begin, I'd like to direct you to the forward-looking statement and suggest that you look at our amost recent SEC filings for some analysis of the risk factors involved in our business.
For this meeting's presentations our featured speaker is Dr. Jedd Wolchok from Memorial Sloan-Kettering Cancer Center, who will review the ipilimumab melanoma data presented at this year's annual meeting of ASCO. With us also are Geoff Nichol, Senior Vice President of Product Development at Medarex, who is to my right, who will provide brief update on the path forward, and Chris Schade, who's all the way to the right of this table, who is of course our CFO and who will direct the Q&A.
And following the updates by Dr. Wolchok and Geoff, we will open the webcast's meeting to Q&A and ending with some final remarks. My name is Howard Pien, I'm the CEO of Medarex. I'm pleased to introduce our first presenter, Dr. Jedd Wolchok, who's a Director of Immunotherapy Clinical Trials at Memorial Sloan-Kettering where's he a medical oncologist specializing in the treatment of melanoma.
He's an Associate Attending Physician on the melanoma sarcoma oncology service, an Associate Director of the Ludwig Center for Cancer and Immunotherapy. Dr. Wolchok received his residency and post doc training from the New York University Medical Center, Bellevue Hospital, and completed fellowships at Memorial Sloan-Kettering Cancer Center.
He's an author of over 70 peer review journal articles, books, book chapters, and review articles. Dr. Wolchok received his MD from the NYU School of Medicine, and his Ph.D. from NYU Graduate School of Arts & Sciences, MBA from Princeton University.
Just a word about the flow of this meeting, first of all, the PDF of all of the slides that we're going to show will be at the Medarex web site. And the flow we expect with the next 55 minutes to be like this, around 25 to 30 minutes for Dr. Wolchok to do the heavy lifting on the data, about four or five minutes with Geoff Nichol on the path forward, which leaves us about 15 minutes for Q&A.
I now turn the session over to Dr. Wolchok.
JEDD WOLCHOK, DIRECTOR OF IMMUNOTHERAPY CLINICAL TRIALS, MEMORIAL SLOAN-KETTERING CANCER CENTER: Thank you, Howard, and good morning to everybody. Thank you for coming out to this meeting and webcast. I'm going to go through the data for ipilimumab in melanoma, both from historical data as well as the data presented at this year's ASCO meeting so far.
In summary, these are the points that we're going to cover. Ipilimumab is a monoclonal antibody that has prolonged overall survival and one-year survival rates, when compared with those datasets from the medical literature for similarly staged patients with metastatic melanoma.
In treating we've observed some new response patterns, and I will get into the specifics later. But these response patterns have not been seen with other cytotoxic cancer therapies, and we have noted them to be associated with prolonged survival from this otherwise lethal diagnosis.
As a result, the investigators in the ipilimumab program feel that the modified World Health Organization and RECIST criteria that are standardly used for judging response to cytotoxic chemotherapy do not adequately capture the clinical activity of ipilimumab and other immunotherapy drugs.
Specifically, new lesions can appear during ipilimumab therapy, which do not always indicate patients who are destined to progress in the course of their disease or indicate treatment failure. In addition, responses may occur many months after initial progression of disease with enlargement of baseline lesions. These patterns of progression followed by response were heretofore not observed in cancer cytotoxic therapy trials.
We believe that 10mg/kg is the optimal dose for ipilimumab given an induction regimen once every three weeks times four followed by maintenance therapy once every three months is patients experience clinical benefit. And the ipilimumab immune related adverse events are largely manageable and reversible with medical therapy, using the simple established treatment algorithms and guidelines that have been developed by Medarex and BMS.
So these are the three studies that were presented at this year's ASCO. And I'm just going to review very briefly what these trials were designed to look at. The so-called 008 trial was a single arm, open-label trial at 10mg/kg, for patients who progressed on or after a prior approved or frequently used therapy for metastatic melanoma. It enrolled 155 patients.
So-called Study 22, which enrolled 217 patients, was a three-arm, randomized, blinded trial of three different doses of ipilimumab ranging from 0.3mg/kg to 3mg/kg up to the optimal dose of 10mg/kg. Similarly, this trial was designed for patients who progressed on prior therapy or who are intolerant to prior therapy because of adverse events.
[Study 7], which was presented yesterday by Dr. Jeff Weber, enrolled 115 patients and allowed patients who were either untreated or progressed on prior therapy. This was a randomized, placebo-controlled trial to look at the effect of budesonide, an orally absorbed -- sorry, orally non-absorbed corticosteroid, in reducing the gastrointestinal side effects of ipilimumab when given at 10mg/kg.
The main eligibility criteria for the three studies are shown on the next slide. And I'll just draw your attention to the fact that the Study 7 allowed both untreated and previously treated patients. Study 7, however, also allowed patients with controlled brain metastases, but that all of these trials were designed for patients with unresectable Stage III or Stage IV melanoma.
The demographics in this study are summarized in the next slide, and I will not go through all of these details. But to just draw your attention to the boxed information, which is testament to the highly advanced nature of the patient population involved in all of these studies.
So M1c melanoma are patients who have metastatic melanoma in unfavorable sites such as bone, liver, brain, or those with an elevated level of lactate dehydrogenase, or LDH, which is indicative of patients with rapidly progressive disease. So in general 50% to 60% of patients in all of these studies had M1c disease. And in fact, close to half of them had an elevated LDH greater than two times the upper limit of normal.
And this would indicate a patient population with rapid progression of melanoma, and those would be expected to have a seven-month or less median survival based upon large historical controlled datasets. I would also draw your attention to the fact that in the bottom-line under any prior systemic therapies, that approximately 35% of patients had greater than two prior therapies.
So, what is the historical data by which we judge the effect of ipilimumab? So summarized in this slide are large historically controlled datasets for the survival of patients with metastatic melanoma. And the line at the top has been referred to in many presentations at ASCO this year, the Korn and Kirkwood analysis that was published in the JCO later this year.
This is a meta-analysis of 42 Phase II trials for patients with Stage IV melanoma. And from this large and now very well reference analysis, there is approximately a 6.2-month median overall survival for patients in Phase II trials with Stage IV melanoma. And similarly, the overall survival at the landmark time of one year is approximately 26%.
You can see that this largely supported by other trials that have been conducted over the past two to three decades, which were listed below that. Which in general show that the median overall survival ranges from 4.6 months up to ten months, depending upon the particular dataset that you look at.
And that in general, if one subsets out patients with an elevated LDH, that results in a better overall survival such as that was shown in the Bedikian paper about the Genasense study, where the overall survival of the population as a whole was 7.8 months. However, if you look at those patients with a normal LDH, the survival is much greater.
To look at what has been seen with ipilimumab so far, and -- just draw your attention to the light yellow boxes, which highlight the 10mg/kg or the optimally dosed patients, the median overall survival and months ranges from ten to 14.6 months in the two Phase II studies, which I refer to. And the overall survival has not been reached in Study 7, which was the randomized trial of budesonide with ipilimumab or ipilimumab alone.
The percent survival at one year is reflective of this prolonged overall survival in this population with one-year survival rates from the high 40s to the high 50% range. And so if we draw your attention back to the last slide with those two facts on the bottom, the historical...
NOTE: All illustrations and photos have been removed from this article.
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