Since at first read, this seems like competition for my beloved Norian, I looked up CBMI. Basically, they are targeting classic long bone non-union fractures that haven't healed, a different market area than Norian targets, at least at this time. Plus, the Norian stuff is structural after 10 minutes (and radioopaque), so these are drastically different products. Norian used to have a program looking at adding Bone Morphogenic Protein to their SRS, but I don't know where that stands......seems like a logical approach to me.
Basically, the big advantage that the CBMI OP-1 has is that it allows the avoidance of an autograft being taken off the hip or elsewhere, thereby avoiding a painful second surgery with its infections, pain, etc.... Plus, the serrated edge they leave on the edge of the Illiac Crest when they take the graft can be pretty irritating. Also, for weight bearing bones such as the femur (not sure about the tibia) it is not uncommon to also have a metal plate put in to stabilize the autograft. I had a girl friend from college who was on the back of a motorcycle of mine when we got hit by a car go through an autograft procedure on her femur after it didn't heal back in 1978, so between that and my Norian days, I'm pretty familiar with it.
I agree with your analysis that the post surgical X-rays are irrelevant, because a bunch of crushed bone will be radioopaque, whereby protein OP-1 and collagen are radiotransparent. However, I'd be more concerned with the later data showing better cortical bridging in the autografts, because by then the OP-1 should have had time to get a decent repair. But, in my mind, the critical endpoint is the functionality, not the x-rays. This seems like a classical example of an analysis (Xray) that should be looked at from a quality standpoint, but that quantification of repair shouldn't be made. The autograft definitely has an xray advantage from the start, and expecting the OP-1 to surpass it might be unrealistic in any time frame. However, the FDA might want to have them do longer term followups (I'm not sure how long they are waiting before checking these endpoints) to see if the OP-1 surpasses it ultimately.
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In a third aspect of the trial, however, results did not come in as expected, he said.
Follow-up x-ray analysis of the fracture repairs -- for both OP-1 and autograft patients -- did not meet the 80-percent success-rate target set before the trial
began, he said.
Further, radiologists asked to judge the success of bone repair in each case, based on x-ray pictures alone, reported better results from the autograft group.
''They did do a little better than the OP group,'' Simpson said.
OP-1 does not show up on x-ray pictures, while bone chips do, raising the possibility that x-ray analysis may be inherently biased, he said.
''We're pretty pleased with these results,'' Simpson said. ''We understand the radiographic assessment didn't turn out as nice as we'd like, but these patients
are healed and back to a productive life. So we're comfortable with the study.''
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What this will come down to at the FDA is that both procedures didn't hit the preconceived mark on radiologic assessment. But, they had good functional outcome. It seems to me that CBMI screwed up on their study design using a analysis that isn't very relevant, and that they missed on. The FDA doesn't always treat this kind of stuff kindly, essentially after the fact tweaking of the endpoints to accomodate the data, especially when it is a replacement treatment for something else that already works and is accepted....autograft. I see a few possible FDA courses of action here. Kick it for a new clinical trial (ugly for CBMI). Require continued followup and a resubmit on the current patients down the road (not so bad). A conditional approval with further followup on these patients and more clinical study after approval (a base hit). Approval (a home run).
The FDA has a tendency, in my mind, to punish poor clinical design, whether efficacy is shown or not, (a kind of rub your nose in it attitude that the scientific method be maintained...make a hypothesis and prove it, don't change the analysis after the fact, even if we let you do a second study doing the analysis the new way) so I would expect the first or second result. I doubt they approve it with out more study as they are just too damn nit-picky and not too concerned with the companies timeframes, financial impact or what seems to be better for the patients, especially in non-lethal situations with a current acceptable procedure. If the clinical design says we will get A, B & C (C being radiologic outcome). Then they achieve A & B, but not quite C, usually gets scorn not approval. After the fact analysis saying that the important outcomes were met, but that we missed on one analysis, but it isn't important anyway usually just annoys the FDA. They will often have you go back and redo with new clinical endpoints. Reasonableness doesn't often figure in with the FDA. But, you just never know.
I'd call this stock a crapshoot.
Rman |
