Alkermes and Genentech Expand Collaboration for Nutropin Depot
Introduction
Injectible, Sustained Drug Delivery for Biopharmceuticals
Other Drug Delivery Interests
Introduction (Back to Top)
On April 15, Genentech Inc. (San Francisco) and Alkermes Inc. (Cambridge, MA) announced a two-year extension and expansion of their collaboration for Nutropin Depot, an injectable sustained release formulation of Genentech's human growth hormone based on Alkermes' ProLease drug delivery system. As anticipated by their original collaboration, initiated in 1995, the companies have completed a Phase III clinical trial of Nutropin Depot for the treatment of pediatric growth hormone deficiency and are preparing to submit a New Drug Application with the U.S. Food and Drug Administration (FDA). Under the revised agreement, the companies will conduct expanded development activities, including clinical trials in an additional indication, process and formulation development, and manufacturing.
The terms of the collaboration include the immediate purchase by Genentech of $35 million of newly issued redeemable convertible exchangeable preferred stock of Alkermes with a conversion price of at least $45 per share. The agreement also includes potential milestone payments to Alkermes of approximately $40 million. Because of the way the financing is structured, Alkermes stockholders will actually see an increase of $17.5 million in R&D expenditures for two years, not an increase in corporate revenues. If everything goes according to plan this will be followed by a $40 million windfall for Alkermes once the preferred stock is retired.
"The combination of preferred stock issuance followed by the milestone payments will essentially be a wash for Alkermes," Pops said during a conference call. "The $35 million will first appear as part of our burn. In the end, when the milestones are paid out, the preferred stock will disappear and we'll come out ahead by about $5 million." Pops stressed that issuing the preferred stock would not result in dilution of Alkermes' existing stock.
"From Alkermes' standpoint, the expansion of our agreement with Genentech will allow us to broaden our development activities, expand our manufacturing base, and explore additional formulations." Securities analysts in on the conference call were more than marginally interested in the "additional formulations" statement by Pops, suggesting perhaps that Alkermes had not yet found the right formula for making ProLease work with human growth hormone. Pops admitted that arriving at the optimal formulation would take some more time, but that the situation was not unusual for a development project at this stage. "Formulation optimization is occurring right now on an experimental basis in animals," he stated.
Injectible, Sustained Drug Delivery for Biopharmceuticals (Back to Top)
ProLease drug delivery enables the formulation of proteins and complex bioactive molecules, normally given by frequent injection, into injectible, sustained-release formulations lasting days to months. In addition to proteins, ProLease is applicable to a wide range of drugs including peptides and water-soluble small molecules.
ProLease is composed of biodegradable microspheres containing the desired bioactive molecule incorporated into a matrix of poly(DL-lactide-go-glycolide) (PLGA), a common medical polymer. This novel package enables the delivery system to address the complex formulation challenges of protein drug delivery: structural complexity and fragility, negligible oral bioavailability, and short plasma half-life.
The technology behind ProLease is a patented cryogenic process designed to assure stability of fragile compounds during the manufacturing process, storage, and release-phase in vivo. A key element of the process is the incorporation of drugs substance in a stabilized solid state at very low temperatures without the use of aqueous solvents or surfactants.
The ProLease process leads to a solid pharmaceutical compound dispersed within a PLGA matrix. The microspheres are packaged in vials as a dry, free-flowing powder and suspended in an aqueous vehicle prior to subcutaneous or intramuscular injection. ProLease manufacturing is performed under aseptic conditions utilizing state-of-the-art isolation technology. Both the process and facilities are compliant with U.S. and international Good Manufacturing Practice (GMP) Requirements. ProLease is readily scaleable to kilogram size batches suitable for commercial requirements. Construction of a commercial scale facility is underway in Cambridge, MA.
Proteins and peptides incorporated into ProLease have shown excellent integrity (as measured by levels of aggregates and degradation products), high incorporation efficiency, and high drug loads. Shelf-life stability has been demonstrated for up to two years.
According to Alkermes, ProLease formulations have the potential to:
- improve patient convenience and compliance.
- broaden medical and commercial opportunities for pharmaceutical products.
- provide access to important new markets currently inaccessible to drugs that require frequent injections.
Clinical trials are underway to demonstrate the safety and efficacy of ProLease for several products.
Other Drug Delivery Interests (Back to Top)
Drug delivery is Alkermes' principal activity. Aside from its growth hormone work with Genentech, the firm is developing products for:
- delivery of drugs into the brain past the blood-brain barrier, utilizing the firm's Cereport technology.
- oral delivery of drugs using its RingCap and DST technologies.
- development of pharmaceutical products based on proprietary pulmonary drug delivery technologies utilizing Alkermes' recently acquired AIR technology.
Headquartered in Cambridge, MA, Alkermes operates manufacturing facilities in Massachusetts and Ohio and a medical affairs office in Cambridge, England.
For more information: Richard F. Pops, CEO, Alkermes Inc., 64 Sidney St., Cambridge, MA 02139. Tel: 617-494-0171. Fax: 617-494-9263.