In a recent Phase2b trial, NicaPlant has proven that it effectively reduces the risk of angiographic and symptomatic cerebral vasospasm after clipping of ruptured cerebral aneurysms. This reduces stroke and costs associated with the treatment of patients with subarachnoid hemorrhage. Also, early clinical outcomes tended to be improved. The next pivotal step on the way of approval of NicaPlant for routine clinical use for patients, whose aneurysms are clipped, is a Phase 3 trial which aims at confirming these benefits.
On the path to realizing this pivotal Phase 3 study, our concept to pursue a novel strategy to prevent vasospasm in patients undergoing aneurysm clipping has been frequently challenged by expert opinions stating that treatment of ruptured aneurysms by microsurgical/open means will not be relevant in the near future (´the market for Clipping is dead´). This statement has always been misleading, if not false, given the evidence available in the literature.
Yesterday, the final results of the prospective, multicenter randomized ISAT-2 trial were published in the Journal of Neurosurgery. Main authors are Tim E. Darsaut and Jean Raymond from Canada. The International Subarachnoid Aneurysm Trial–2 was a randomized trial comparing surgical versus EVT (endovascular treatment) of ruptured intracranial aneurysms considered for surgical clipping, despite the results of previous randomized controlled trials, and also eligible for EVT.
The primary endpoint was death or dependency according to the modified Rankin Scale score (mRS score > 2) at 1 year. Secondary endpoints included 1-year angiographic results and length of hospital stay. The primary hypothesis was that endovascular management would decrease the number of poor outcomes (mRS score > 2).
The results of ISAT-2 draw a different view on the future of open microsurgical therapy and can be summarized as follows:
Already 1 year after treatment of Subarachnoid Hemorrhage Clipping proves superior to EVT
clinical outcome: Clipping = EVT (mRS>2 30% vs 27%)
complete aneurysm occlusion: Clipping superior to EVT (80% vs 50%)
residual aneurysm: Clipping superior to EVT (20% vs 8%)
more retreatment: Clipping superior to EVT (retreatment associated with unfavorable outcome)
repeat aneurysm rupture Clipping superior to EVT (1% vs 4% – 80% fatal)
Important for future treatment with NIicaPlant
Symptomatic vasospasm was more common with surgery, with the number of patients requiring EVT of vasospasm being similar. Thus, cerebral vasospasm in patients undergoing clipping contributes to high and costly therapy intensity levels and unfavorable individual treatment results for patients with subarachnoid hemorrhage.
How does this all translate into BIT Pharma´s treatment concept with NicaPlant:
- Ruptured aneurysms will be continued to be treated with clipping
- Most likely, the market for clipping will increase, and not decline
- Especially following clipping, prevention of vasospasm is currently a most valuable treatment goal and clinical need
- Prevention of vasospasm with NicaPlant may further improve clinical outcome (especially for surgical patients)
