FACED WITH HIGH COSTS, long development times, regulatory uncertainty and the need to differentiate products, pharmaceutical manufacturers are banking on drug delivery to deliver value. Drug delivery is “the great equalizer,” perhaps the only area of drug development where small players can trump mega-pharmas.
At its best, drug delivery achieves many of the goals of medicinal chemistry: solubilizing oily molecules, improving bioavailability and pharmacokinetics, allowing more favorable dosing over time, and targeting drugs to tissues – all while lowering doses and reducing side effects.
Fuji-Keizai USA estimates the 2002 global market for drug delivery systems at $47 billion, rising to $67 billion in 2006 based on estimated growth of about 8% per year. With blockbuster drugs losing $37 billion to generics between 2002 and 2006, the argument for innovative delivery of old treatments has never been better.
Enhancing already-approved drugs through drug delivery mitigates much of the risk associated with discovery, development, testing and approval, according to George Haley, Ph.D., at the University of New Haven’s Department of International Business. As such, drug delivery becomes both an offensive and defensive strategy. “R&D-based pharmaceutical firms depend on the flow of new drugs out of their pipelines – a difficult, risky enterprise made a lot less risky through new forms of products already known to be safe and effective,” Haley observes.
Perhaps the most prominent, technologically compelling example is PEGylation of proteins and peptides as practiced by Nektar Therapeutics (San Carlos, Calif.).
Through PEGylation, polyethylene glycol residues are chemically attached to peptides and proteins to improve pharmacokinetics and absorption. The company’s main approved PEGylation products include Neulasta (with Amgen) to boost white blood cell counts, PEGASYS PEGylated interferon (with Roche), and Macugen (with Pfizer), the first U.S.-approved PEGylated oligonucleotides, for treating macular degeneration.
Nektar has defined diabetes as a key therapeutic area. “Many peptides for treating the disease can be improved with less invasive or noninvasive delivery,” says Chris Searcy, Pharm.D., VP of corporate development.
Pharma Unit Operations Becoming Commoditized
“A fundamental goal of the pharmaceutical business is to manage product lifecycles,” says Jan Paul Zonnenberg, a director at consulting firm PRTM (Waltham, Mass.). That is becoming more difficult to do with conventional oral dosage forms and their associated unit operations, which Zonnenberg sees as becoming commoditized.
“Manufacturers no longer hold a competitive advantage by focusing on roller compaction, direct compression or fluid bed granulation,” he says. The key is to maintain competencies for developing new drugs and dosage forms, and to outsource the rest.
Advanced delivery systems, however, are still in their growth phase, so companies prefer to retain control over them, regardless of whether the technology is licensed or home-brewed. They might still outsource out of necessity. “Not because it’s cheaper or faster, but for capacity or capability reasons,” Zonnenberg adds. Such decisions are usually based on business tactics rather than long-term strategy.
Delivery enhancement adds steps to the manufacturing process, and if in-licensed, demands considerable technology transfer from the licensor to the innovator. This raises more delicate collaboration issues than, say, the outsourcing of a mature or generic active pharmaceutical ingredient.
|Shown here, assembly cleanrooms for ITI’s intranasal delivery device. Photo: ITI.
Within the old specialty-delivery business paradigm, delivery companies are rewarded through royalties, a model that provides steady but unspectacular revenues. More recently, these firms – as well as manufacturers of generic drugs – have begun to tap into the vast pool of generic medications to manufacture (and in some cases market and sell) products developed in house.
For example, delivery specialty company Labopharm (Laval, Quebec) applied its Contramid controlled-release technology to tramadol, a non-opioid analgesic, while Biodelivery Sciences (BDSI; Morrisville, S.C.) has begun to offer fentanyl, an established treatment for breakthrough pain, via its BEMA oral adhesive-disk delivery platform.
According to BDSI CEO Mark A. Sirgo, Pharm. D., BEMA shines in rapid-onset applications, like analgesia for cancer or trauma patients, where intravenous delivery is impractical. BDSI’s oral fentanyl patch competes with Cephalon’s Actiq fentanyl lozenge, which enjoys sales of more than $400 million a year. Actiq is delivered to the oral mucosa through a lollipop-like device held in place by the patient.
A similar model is followed by Access Pharmaceuticals. Inc. (Dallas, Texas), which promotes in-licensed oncology compounds to late-stage clinical trials, then seeks a commercialization partner. The company’s water-soluble, polymer-based delivery platform allows high dosing directly to tumors. In the bloodstream, the polymer protects healthy cells from the drug. The lower pH inside cancer cells cleaves the polymer to release the active material. Access’ lead product, AP5346, a polymer-modified platinate oncology drug, is in Phase II testing. According to David Nowotnik, Ph.D., senior VP of R&D, this strategy allows 10-fold higher dosing compared with cisplatin, an old-line chemotherapy drug.
Depomed (Menlo Park, Calif.) has adopted a business strategy that John Shell, VP of operations, describes as “opportunistic”: creating new products from established drugs through value-added delivery technology.