Ipilimumab survival benefit confirmed in phase 3 trial

Thanks for posting this link. Phil did Ipi w/o vaccine last fall but doesn't appear to be a responder. We are waiting to hear if he is positive for the B-RAF mutation. If he isn't I am going to take this article to discuss with his onc to see if he can also get the vaccine to maybe give the Ipi a hand. We shall see. But thanks for the info.

Thanks for posting this link. Phil did Ipi w/o vaccine last fall but doesn't appear to be a responder. We are waiting to hear if he is positive for the B-RAF mutation. If he isn't I am going to take this article to discuss with his onc to see if he can also get the vaccine to maybe give the Ipi a hand. We shall see. But thanks for the info.

Thanks – It was good to see Dr Minor (a local doc in San Francisco) on the report you mentioned above.  Before Ipi was approved for compassionate use last year, and before the 2010 ASCO conference when these trial results were released, I found that most of the info on the drug was being covered by investment blogs.  Today I saw a good one on Ipi and BMS and the upcoming FDA approval. 

http://seekingalpha.com/article/254773-bristol-myers-squibb-outstanding-pipeline-makes-it-most-attractive-among-large-pharmaceuticals

FROM THE ARTICLE

Ipilimumab is First Up on the News Front

The March 26 PDUFA date is imminent for ipilimumab and I have chosen to focus on it for that reason. It is a new immunological therapy following on the trail of Provenge although the two drugs work quite differently. It has the potential to be a multi-billion product. Ipilimumab has demonstrated a survival advantage in second line metastatic melanoma is and the first ever drug to show a survival benefit in any stage of metastatic cancer.

Ipilimumab is a monoclonal antibody that acts on the CTLA-4 receptor that is found on T-cells and activates them. This is different from other targeted therapies and the recently approved cancer vaccine Provenge which target antigens on the cancer cell. The mechanisms of action of both Provenge and ipilimumab are intended to increase T-cell activity against a tumor.

The Addressable Market for Ipilimumab in Metastatic Melanoma

Metastatic melanoma is estimated to affect 40,000 patients each year in the U.S. and 60,000 in the rest of the world. Half of the patients are younger than 59 years of age and many die in less than a year. There is currently no effective therapy. Although ipilimumab will initially be approved in a second line setting, this disease progresses so rapidly that most metastatic cancer patients will see it during the course of their disease. A trial in first line metastatic melanoma should report results in the near term. I believe it will be successful and lead to approval in the first line setting as well.

What will the price be? Some have speculated that it might be priced at $93,000 per year like Provenge. I don’t think so. Provenge can get away with this price because it does not require supportive care which in the case of some therapies can be as much as the cost of the drug. Ipilimumab has some serious side effect issues that will require extensive supportive care and it will also be used in combination with other expensive treatments unlike Provenge which is used alone.

I am guessing that ipilimumab will be priced at $50,000 per course of therapy. This makes for an addressable market for metastatic melanoma of $2 billion in the U.S. and $3 billion in the rest of the world. I think that ipilimumab will capture a very significant share of this market and conservatively see it as having $1 to $2 billion of peak sales potential in metastatic melanoma. These estimates assume acute use of the drug, but there may be a role in maintenance which would substantially increase sales potential. It may potentially also be used in other types of tumors and this could create additional sales potential.

Ipilimumab in Metastatic Melanoma

The company reported encouraging results in its study 020 of metastatic melanoma at the June 2010 ASCO meeting; this trial was started in 2003. The study involved ipilimumab in combination with an experimental cancer vaccine targeted at gp 100, a protein present on melanoma cells. It was a double blinded 3 to1 to 1 randomization which means that for every five patients that went into the study, three went to the combination of ipilimumab and gp 100, one to ipilimumab alone and one to the gp 100 vaccine alone. There were 403 patients in the ipilimumab plus gp 100 group, 137 in the ipilimumab only group and 136 in the gp 100 group.

The study population in the 020 trial was called a second-line population, but in reality many patients had received multiple lines of therapy and were in fact third line or refractory. They were very sick patients with poor prognosis. This population is truly representative of patients who have received multiple drug treatments and have not responded.

After two years of treatment, 24% of patients treated with ipilimumab were still alive compared to 22% in the ipilimumab combined with gp 100 group and 14% in the gp 100 only group. These comparisons were highly statistically significant and provide robust evidence of effect. Basically, the vaccine did not add to the therapeutic effect of ipilimumab, nor detract based on this data. Importantly, the number of deaths in the trial after two years seemed to plateau for the ipilimumab arms Optimists would say that this is suggestive that as many as 20% of patients may have benefited from something approximating a cure. As of the ASCO meeting there were 94 patients who had survived two years or more.

There are significant safety issues with ipilimumab and it caused deaths in the 020 trial. The mechanism by which this drug induces activity, the proliferation of T-cells, also leads to serious side effects. In terms of deaths related to the mode of action of the drug, the total number of deaths in the study was seven; five in the combination arm and two in the ipilimumab alone arm. As investigators learned how to detect the symptoms of immuno-related adverse reactions sooner, management could be introduced earlier, and there was a better chance of averting severe side effects. The incidence of toxicity diminished as more was learned about detecting adverse events at an early stage and preventing or managing them.

BMY is covering all aspects of melanoma. A second study, 024, is a being done in first-line treatment of metastatic disease. The study has already completed accrual, and BMY is awaiting results based in events. The primary end point is overall survival. Results from this trial could come at any time. It was originally thought that the 024 study would report out in late 2010. However, the required number of deaths required to stop the trial and analyze the data has not yet occurred. This study compares the standard of care (decarbizine) in combination with ipilimumab to standard of care alone.

Thanks – It was good to see Dr Minor (a local doc in San Francisco) on the report you mentioned above.  Before Ipi was approved for compassionate use last year, and before the 2010 ASCO conference when these trial results were released, I found that most of the info on the drug was being covered by investment blogs.  Today I saw a good one on Ipi and BMS and the upcoming FDA approval. 

http://seekingalpha.com/article/254773-bristol-myers-squibb-outstanding-pipeline-makes-it-most-attractive-among-large-pharmaceuticals

FROM THE ARTICLE

Ipilimumab is First Up on the News Front

The March 26 PDUFA date is imminent for ipilimumab and I have chosen to focus on it for that reason. It is a new immunological therapy following on the trail of Provenge although the two drugs work quite differently. It has the potential to be a multi-billion product. Ipilimumab has demonstrated a survival advantage in second line metastatic melanoma is and the first ever drug to show a survival benefit in any stage of metastatic cancer.

Ipilimumab is a monoclonal antibody that acts on the CTLA-4 receptor that is found on T-cells and activates them. This is different from other targeted therapies and the recently approved cancer vaccine Provenge which target antigens on the cancer cell. The mechanisms of action of both Provenge and ipilimumab are intended to increase T-cell activity against a tumor.

The Addressable Market for Ipilimumab in Metastatic Melanoma

Metastatic melanoma is estimated to affect 40,000 patients each year in the U.S. and 60,000 in the rest of the world. Half of the patients are younger than 59 years of age and many die in less than a year. There is currently no effective therapy. Although ipilimumab will initially be approved in a second line setting, this disease progresses so rapidly that most metastatic cancer patients will see it during the course of their disease. A trial in first line metastatic melanoma should report results in the near term. I believe it will be successful and lead to approval in the first line setting as well.

What will the price be? Some have speculated that it might be priced at $93,000 per year like Provenge. I don’t think so. Provenge can get away with this price because it does not require supportive care which in the case of some therapies can be as much as the cost of the drug. Ipilimumab has some serious side effect issues that will require extensive supportive care and it will also be used in combination with other expensive treatments unlike Provenge which is used alone.

I am guessing that ipilimumab will be priced at $50,000 per course of therapy. This makes for an addressable market for metastatic melanoma of $2 billion in the U.S. and $3 billion in the rest of the world. I think that ipilimumab will capture a very significant share of this market and conservatively see it as having $1 to $2 billion of peak sales potential in metastatic melanoma. These estimates assume acute use of the drug, but there may be a role in maintenance which would substantially increase sales potential. It may potentially also be used in other types of tumors and this could create additional sales potential.

Ipilimumab in Metastatic Melanoma

The company reported encouraging results in its study 020 of metastatic melanoma at the June 2010 ASCO meeting; this trial was started in 2003. The study involved ipilimumab in combination with an experimental cancer vaccine targeted at gp 100, a protein present on melanoma cells. It was a double blinded 3 to1 to 1 randomization which means that for every five patients that went into the study, three went to the combination of ipilimumab and gp 100, one to ipilimumab alone and one to the gp 100 vaccine alone. There were 403 patients in the ipilimumab plus gp 100 group, 137 in the ipilimumab only group and 136 in the gp 100 group.

The study population in the 020 trial was called a second-line population, but in reality many patients had received multiple lines of therapy and were in fact third line or refractory. They were very sick patients with poor prognosis. This population is truly representative of patients who have received multiple drug treatments and have not responded.

After two years of treatment, 24% of patients treated with ipilimumab were still alive compared to 22% in the ipilimumab combined with gp 100 group and 14% in the gp 100 only group. These comparisons were highly statistically significant and provide robust evidence of effect. Basically, the vaccine did not add to the therapeutic effect of ipilimumab, nor detract based on this data. Importantly, the number of deaths in the trial after two years seemed to plateau for the ipilimumab arms Optimists would say that this is suggestive that as many as 20% of patients may have benefited from something approximating a cure. As of the ASCO meeting there were 94 patients who had survived two years or more.

There are significant safety issues with ipilimumab and it caused deaths in the 020 trial. The mechanism by which this drug induces activity, the proliferation of T-cells, also leads to serious side effects. In terms of deaths related to the mode of action of the drug, the total number of deaths in the study was seven; five in the combination arm and two in the ipilimumab alone arm. As investigators learned how to detect the symptoms of immuno-related adverse reactions sooner, management could be introduced earlier, and there was a better chance of averting severe side effects. The incidence of toxicity diminished as more was learned about detecting adverse events at an early stage and preventing or managing them.

BMY is covering all aspects of melanoma. A second study, 024, is a being done in first-line treatment of metastatic disease. The study has already completed accrual, and BMY is awaiting results based in events. The primary end point is overall survival. Results from this trial could come at any time. It was originally thought that the 024 study would report out in late 2010. However, the required number of deaths required to stop the trial and analyze the data has not yet occurred. This study compares the standard of care (decarbizine) in combination with ipilimumab to standard of care alone.