David A. Roth

Reformulated BeneFix®: efficacy and safety in previously treated patients with moderately severe to severe haemophilia B

Summary.   BeneFix®, the only recombinant factor IX (FIX), has been reformulated. The reformulation involves a change in diluent and allows for more concentrated infusions of recombinant FIX. A double‐blind, randomized, pharmacokinetic (PK) crossover study demonstrated that reformulated BeneFix was bioequivalent to original BeneFix and follow‐up PK evaluation after 6 months of treatment demonstrated the PK stability of reformulated BeneFix after multiple exposures. Favourable efficacy and safety profiles, consistent with those already well‐established for original BeneFix, were observed: 81.1% of haemorrhages resolved with only a single infusion; 85.3% of initial treatment response ratings were Excellent or Good; more than half of the subjects using reformulated BeneFix for routine prophylaxis (11 of 17, 64.7%) had no spontaneous haemorrhages during their 6–12 month course of prophylactic treatment, with an overall spontaneous bleeding rate of 0.72 year−1; and for the single surgical procedure (knee washing), treatment was rated Useful. In addition, there was no FIX inhibitor development, allergic‐type manifestations, or thrombogenic complications with more than 1100 infusions (nearly 5.2 million IUs) administered in this trial. All efficacy and safety outcomes from this study were achieved with more concentrated recombinant protein infusions than that possible with original BeneFix, and utilization of the 2000 IU per vial dosage strength, newly introduced with the reformulated product, was high (>62%). The reformulation of BeneFix allows smaller delivery volumes and an increased choice of dosage strengths without altering the PK properties (including incremental recovery and half‐life) or the established efficacy and safety profile of recombinant FIX.

Occlusion of Intracranial Aneurysms by Ferromagnetic Thrombi

The rupture of intracranial aneurysms is a major cause of strokes, but present operations to repair aneurysms and to prevent their recurrent rupture are plagued by high morbidity and mortality rates. A simpler and safer operation is proposed utilizing two permanent magnet‐tipped probes introduced through a small opening in the skull and guided under x‐ray control to lie near the aneurysm. The magnets attract ferromagnetic emboli injected into the cerebral circulation through the internal carotid artery in the neck, eventually filling the aneurysm. Following the formation of a blood clot which would reinforce the aneurysm wall against rupture, the probes would be withdrawn. Simulated aneurysms were occluded with three‐micron carbonyl‐iron particles injected upstream from two 5‐mm‐diameter, bullet‐shaped Alnico V magnets applied at the aneurysmal opening. The same particles injected into the intracranial circulation of animals did not obstruct the capillaries and produced no detectable clinical, physiologic...