Emisphere Technologies Inc. presented results on Tuesday ofan initial human safety study of its proprietary oral drugdelivery system (ODS) at the Seventh Annual Meeting of theAmerican Association of Pharmaceutical Scientists in SanAntonio, Texas.
The oral administration of Emisphere's system, whichencapsulates a low molecular weight heparin (LMWH), wasshown to be safe, and the compound's activity was comparableto that measured in preclinical trials in non-human primates,the Hawthorne, N.Y., company (NASDAQ:EMIS) said.
ODS is a patented technology developed by Emisphere based onthe ability to encapsulate therapeutic agents in microspherescomposed of amino acids. The microspheres allow drugs to beabsorbed unchanged into the bloodstream while protectingthem from the harsh environment of the gastrointestinal tract.
"We've tested close to two dozen drugs without any damage tothe therapeutic value of each drug as a consequence of beingdelivered in our system," said Sam Milstein, Emisphere's chiefscientific officer.
Using this delivery technique, Emisphere reported 20 percentbioavailability of LMWH, which should please the company'spotential licensing partners. "All our potential partners haveset commercial targets that range between 5 and 15 percentbioavailability," Milstein said.
"It (Emisphere's ODS) is a holy grail of delivery systems," saidDavid Steinberg, an analyst with Volpe Welte in San Francisco."The data says the system is able to deliver and administerwithout toxicity, and now the question is, can it be delivered ina reliable and safe manner?"
A safe and reliable oral drug delivery system must be able toencapsulate a protein so it is not degraded by enzymes in thestomach, and effectively transport the protein across thegastrointestinal tract without diminishing compound'stherapeutic value, according to Steinberg.
Large proteins must be injected because they are unstable inthe gastrointestinal tract. Since the proteins are quickly brokendown in the body, these injections may be necessary asfrequently as twice daily.
Oral drug delivery systems that are able to deliver largeproteins could expand the current market for certain drugs andreduce costs, especially for chronically ill, non-terminalpatients, said Steinberg.
Enzytech Inc. of Cambridge, Mass., is also developing oral drugdelivery systems. The company is currently in preclinicalstudies with its OraLease system that uses a biodegradable,non-toxic product as the encapsulating polymer matrix. Thepolymer can be modified to alter both the release profiles ofthe incorporated protein and the ability of the microspheres toadhere to or penetrate the intestinal wall.
The company plans to file an investigational new drug (IND)application for OraLease in the first quarter of 1993 andexpects to enter clinical trials using the product in the secondquarter.
Cortecs Ltd. of Middlesex, England, is developing oral peptidedelivery systems. Its Macromol process is a water-in-oilmicroemulsion that transports the polypeptide safely into thebloodstream through the lymphatic absorption system. Thecompany's Bridgelock approach administers a polypeptide withphospholipids to create a "phospho-lipoprotein," which, in anoily medium, will cross cell membranes by a non-receptormediated mechanism. Cortecs was the first company to enterhuman clinical studies with an oral drug delivery product,according to industry sources.
Alza Corp. of Palo Alto, Calif., has developed an oral "push-pill"osmotic system called OROS. It is designed to deliver largequantities of drugs continuously at controlled rates and lessfrequently, and may permit lower doses of some drugs to beeffective.
According to Steinberg, there is skepticism about oral drugdelivery systems because conventional wisdom says you can'tsafely and reliably absorb large peptides through thegastrointestinal tract. "People will watch this field with interest;scientists say expectations are unrealistically high," he said.
But Emisphere's Milstein said, "Although the needle will alwayshave its place, the ODS will win out in those situations where apatient must take a drug for an extended period of time."
Emisphere stock was down $2.38 a share on Tuesday to $20.88.
-- Michelle Slade Associate Editor
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