Banker, the combination trial that Amgen ran showed efficacy, but it wasn't a head to head trial. It was just the combination of CD22 and Rituxan. The data was only a little better than Rituxan alone, so there was no way to know if or how much CD22 added to Rituxan for the efficacy seen.
I talked to a highly regarded researcher about that trial and he said that that many the NHL patients that Amgen used in that trial would not have responded well with Rituxan alone. He gave me reasons, some had a high count of something that made them poor candidates for Rituxan and several others had had Rituxan and had had very short responses, also being very poor candidates for repeat Rituxan use. Given the makeup of the patient population, he felt that the responses that group were very good. However, after that phase ll combination trail, Amgen supposedly tried to negotiate WW rights for E-mab and they and the company never could come to terms and Dr. Goldenberg announced that he was in negotiations to get it back. That took many months.
To do a pivotal trial the right way, double blind, head to head with Rituxan, would be very expensive. Another problem is that Rituxan is being used in combination with lots of other drugs and CHEMO's, making a moving target out of it. Lets say that you show that the combination of Rituxan and CD22 gets a 32% CR rate and Rituxan alone gets an 18% CR rate in a double blind head to head study. The FDA could ask how CD22/Rituxan would compare to a Rituxan/Chemo that is getting a 26% CR rate. Or, if Rituxan is given weekly 8 times instead of weekly 4 times (which they have started doing). You could spend $35 million only to find that the bar had been moved.
This is where autoimmune comes in. Since autoimmune isn't generally a fatal disease, and there isn't a standard of care for most indications, all you have to show is safety and efficacy. The bar is much lower, and at the same time, there is almost nothing out there that has worked in autoimmune. It is the way to go with CD22 in my opinion, and it appears that is the strategy. |
