Alkermes Releases Abstract Regarding Clinical Data for Medisorb Naltrexone.

Business Editors & Health/Medical Writers

CAMBRIDGE, Mass.--(BW HealthWire)--Nov. 21, 2000

Data from first clinical trial of injectable sustained release

formulation of alcoholism drug to be presented at December 2000

scientific meeting

Alkermes, Inc. (NASDAQ: ALKS) today released the attached abstract summarizing results from the first clinical trial of Medisorb(TM) Naltrexone, the company's proprietary injectable sustained release formulation of naltrexone. The abstract was prepared for the 39th Annual Meeting of the American College of Neuropsychopharmacology (ACNP) in December 2000. At that meeting, additional data from the clinical trial will be presented by Alkermes scientists.

Naltrexone is an FDA approved drug used for the treatment of alcoholism and opiate abuse, and is currently available in a daily oral dosage form. Medisorb Naltrexone is a proprietary formulation of naltrexone based on Alkermes' Medisorb injectable sustained release drug delivery technology and is designed to provide once a month dosing. Medisorb Naltrexone is designed to enhance patient compliance by removing the need for daily dosing and providing appropriate drug levels over a one month period.

"We are very pleased with the results of our first clinical trial of Medisorb Naltrexone and look forward to presenting the results," said Richard F. Pops, Chief Executive Officer of Alkermes.

In September 2000, Alkermes announced that it had (i) completed enrollment in a 42 subject double-blind, placebo-controlled study designed to test the safety and pharmacokinetics of a range of Medisorb Naltrexone doses, (ii) analyzed preliminary data from all subjects, and (iii) begun scale up of its manufacturing processes and facilities in Wilmington, Ohio in preparation for larger efficacy trials.

Medisorb is one of Alkermes' proprietary injectable sustained release drug delivery technologies. The technology is based on the encapsulation of drugs into small polymeric microspheres which degrade slowly and release drugs at a controlled rate following subcutaneous or intramuscular injection. Alkermes is developing proprietary Medisorb product candidates and is also developing candidates in collaboration with pharmaceutical and biotechnology companies. The company's leading Medisorb product candidate is a formulation of Janssen Pharmaceutica's antipsychotic drug RISPERDAL that is in Phase III clinical trials. Medisorb Naltrexone is Alkermes' first proprietary product candidate based on the technology.

The Medisorb Naltrexone project has been funded in part with Federal funds from the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health.

Alkermes is a leader in the development of products based on sophisticated drug delivery technologies. The company has several areas of focus, including (i) controlled, sustained release of injectable drugs lasting several days to several weeks, utilizing its ProLease(R) and Medisorb technologies and (ii) the development of pharmaceutical products based on proprietary pulmonary drug delivery technologies utilizing its AIR(TM) technology. In addition to its Cambridge, Massachusetts headquarters, research and manufacturing facilities, Alkermes operates research and manufacturing facilities in Ohio and a medical affairs office in Cambridge, England.

Certain statements set forth above may constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Although Alkermes believes that such statements are based on reasonable assumptions within the bounds of its knowledge of its business and operations, there can be no assurance that: (i) clinical trials of the company's product candidates will be successful, completed on a timely basis, or at all, (ii) the company's partners will continue development of any product candidate to the point of receiving marketing approval from regulatory authorities, or (iii) the company's product candidates will be commercialized successfully.

Alkermes' business is subject to significant risks and there can be no assurance that actual results of the company's development activities and its results of operations will not differ materially from its expectations. For information with respect to other factors which could cause actual results to differ from expectations, reference is made to the reports filed by the Company with the Securities and Exchange Commission under the Securities Exchange Act of 1934, as amended.

SUSTAINED, 30 DAY THERAPEUTIC LEVELS OF NALTREXONE IN A PHASE I CLINICAL STUDY

Chester Osborn, Dave Benziger, Jane Henderson, Elliot Ehrich, Timothy Mant, Raymond Bartus:

Alkermes Europe, Ltd, Cambridge, UK; Alkermes, Inc., Cambridge, MA; Guys Hospital, London, England

While naltrexone can be efficacious in the treatment of alcohol and opiate dependence, its efficacy is greatly limited by poor compliance. Efforts to develop an injectable, sustained release formulation of naltrexone have been pursued for decades, with only modest success to date. Problems of achieving adequate blood levels (e.g., greater than 2 ng/ml) for sufficient duration (e.g.,1 month), without the characteristic high `burst' of released drug within the initial 48 hrs have proven difficult obstacles to overcome. Yet, NIDA, NIAAA, the U.S. Justice Department and The Office of National Drug Control Policy continue to endorse the clinical importance of having an effective and acceptable sustained release formulation available for patients. For this reason, we are developing a sustained release formulation of naltrexone encapsulated into biodegradable, polylactide co-glycolide polymer microspheres that are designed to be injected subcutaneously or intramuscularly.

In a Phase I study, 8 cohorts of 6 subjects were randomized to placebo (N=1/cohort), Medisorb Naltrexone (150, 300, 600 mg SC; 150, 300, 600, 900 mg IM; N=5/Cohort), or 50 mg PO (N=5) in a double blind fashion. Patient safety and plasma naltrexone levels were monitored for up to 56 days following dosing. A preliminary analysis of the results revealed no serious or severe adverse events.

A preliminary pharmacokinetic analysis of plasma naltrexone revealed that both the AUC (0 to 28 days) and Cmax were dose-proportional, with slightly higher values observed with IM dosing (e.g., AUC (SC): 31+/-11, 65+/-13, and 145+/-28 ng d/ml @ 150, 300 and 600 mg, respectively; AUC (IM): 49+/-9, 84+/-12, and 189+/- 27 ng d/ml @ 150, 300 and 600 mg, respectively). The initial burst (within 48hrs) exhibited a peak concentration of only about 3 times the steady state levels (in contrast to differences between peak and minimal daily levels of greater than an order of magnitude with PO naltrexone). Additionally, steady state levels were dose proportional, within expected therapeutic levels and were maintained for a full month following each injection. Levels of 6-(beta)-naltrexol (naltrexone's major metabolite) were approximately two times higher than naltrexone levels under all injectable dosing conditions and several fold lower than those following oral naltrexone.

An injectable, sustained release formulation of naltrexone should offer several unique advantages to alcohol and opiate-dependent patients. In addition to greatly improving compliance, it may produce a lower incidence of adverse effects by avoiding the high daily peak levels of naltrexone and 6-(beta)-naltrexol associated with oral administration of naltrexone. Moreover, the initial high burst typically associated with sustained release formulations has been significantly reduced, while the duration of steady-state release has been extended to a full month. In sum, the relatively high, sustained levels of plasma naltrexone offer reason to be optimistic that therapeutic effects can be maintained for a full month following each injection.