Replies to post #976 on SurModics Inc (SRDX)

[Democritus_of_Abdera]

Fab fragment release from SRDX polymers.

There are at least 5 presentations at the upcoming ARVO meeting which describe release kinetics and safety of SRDX polymers.

See: http://www.abstractsonline.com/viewer/?mkey=%7B0AEC998A%2D0BCA%2D41AF%2DA530%2D43715608C824%7D

Two of the abstracts describe release kinetics of anti-goat Fab fragments from biodegradable polysaccharide devices. One of the divices was a rod intravitreal implant, 5 mm in length and 0.5 mm in diameter, with a biodegradable coating formulated from low molecular weight polysaccharides. The other was an I-vation intravitreal implant coated with a blend of biodegradable polyethylene glycol polymers. Good in vivo release kinetics is described for the first 4 weeks after implantation.

The other three abstracts reference Triamcinolone release. One of the abstracts reports that the I-vation TA intravitreal implants are well tolerated and associated with improvements in macular thickness. Another describes controlled release of Triamcinolone for up to a year from a biodegradable polymer. The third evaluates the safety of a subretinal implant containing Triamcinolone.

Surmodics has reserved a booth in the exhibit hall.

The ARVO meetings will be held May 6-10, 2007 in Fort Lauderdale, Florida. The Association for Research in Vision and Ophthalmology and is a major meeting for both academic and clinical professionals.

[Democritus_of_Abdera]

Genentech had examined the value of using controlled-release microspheres for intra-vitreal antibody administration in the late 1990’s. They apparently concluded that there was no advantage of sustained release formulations over direct injection; the long half-life of IgG in the vitreous being sufficient to prolong its therapeutic availability. Perhaps the experience gained in these studies has biased Genetech against seeking a collaboration with SRDX.

See:

Mordenti J, Thomsen K, Licko V, Berleau L, Kahn JW, Cuthbertson RA, Duenas ET, Ryan AM, Schofield C, Berger TW, Meng YG, Cleland J. (1999). Intraocular pharmacokinetics and safety of a humanized monoclonal antibody in rabbits after intravitreal administration of a solution or a PLGA microsphere formulation. Toxicol Sci. 1999 Nov;52(1):101-6.

Department of Experimental Therapeutics, Genentech, Inc., South San Francisco,
California 94080, USA. [e-mail]

“Poly(lactic-co-glycolic) acid (PLGA) bioresorbable microspheres are used for controlled-release drug delivery and are particularly promising for ocular indications. The objective of the current study was to evaluate the pharmacokinetics and safety of a recombinant human monoclonal antibody (rhuMAb HER2) in rabbits after bolus intravitreal administration of a solution or a PLGA-microsphere formulation. ....”

“This antibody was selected to serve as a model compound for evaluation of in vitro and in vivo release kinetics of a large molecular weight protein (~148 kD) from PLGA microspheres, rhuMAb HER2 was encapsulated in PLGA using a patented 2-step, spray freeze-drying microencapsulation process (Johnson et al., 1996)....”

“Finally, rhuMab HER2 was cleared slowly from the vitreous compartment; the PLGA formulation did not offer any pharmacokinetic advantage over the solution formulation. The long terminal half-life (~5.6 days) suggests that injections of a therapeutic antibody in solution every 1 or 2 months may provide adequate concentrations without further formulation work....”