Anthony Almada, B.Sc.10.01.04
Old Dogs, New Tricks, Bigger Hoops
The allure of creating an economic advantage with ostensibly “generic” ingredients is gaining momentum and is fueling industrial and academic investment.
ByAnthony Almada, B.Sc., M. Sc.
The pain of patent expiration is the bane of pharma and its blockbuster drugs. In the world of nutraceuticals very few single molecule composition “drug” patents exist, wherein the actual molecule is patented (meaning that one could actually be sued for patent infringement simply by manufacturing or importing it). Chromium picolinate and zinc-carnosine are two of the very few examples of such chemical patents. Do proprietary strategies exist to teach commodity, generic ingredients new competitive tricks?
Glucosamine (in its various chemical forms) commands a royal share of dietary supplement sales in virtually all distribution and selling channels. Despite the chemical heterogeneity, e.g. glucosamine sulfate X is not always chemically identical to glucosamine sulfate Y, the marketer and consumer perception is one of chemoequivalence. Moreover, the hydrochloride form may be the market-preferred form due to economic, not evidence-based factors. The ongoing, NIH-funded GAIT (Glucosamine/Chondroitin Arthritis Intervention Trial) study is comparing glucosamine hydrochloride (Gch), chondroitin sulfate (CS), celecoxib (Celebrex®), Gch + CS, and placebo within a starting population of almost 1600 subjects with osteoarthritis. Several bets have been placed on Gch, with potentially prodigious returns or disappointment.
Cargill executed on a directive to produce Gch from a non-shellfish source (fermentation of grain-derived glucose; Regenasure®) and pursue GRAS status. Although there is a dearth of literature suggesting that glucosamine of shellfish origin elicits hypersensitivity/allergic reactions, the perception of this alternative source being more desirable may work to Cargill’s benefit. (Note: The provider of the Gch being used in GAIT is not Cargill.) If the results show that Gch or Gch + CS is significantly more effective (including greater tolerability relative to Celebrex), relative to one or more of the other active arms of the trial, the ensuing top tier news coverage could catapult Gch and Regenasure into rarefied air typically reserved for Sir Edmund Hillary and Tenzing Norgay.
The adoption of Gch into conventional food forms may not foster the birth of products like Joint Loops™ or Arth-A-Roni™ but a product landscape shift is not unfathomable. If the Gch arms fail in GAIT, that too could engender an exodus of mild to moderate proportions if CS alone was shown to prevail. The nagging question that has never been robustly addressed relates to the efficacy of Gch compared to glucosamine sulfate (GS). The bulk of the evidence rests with a specific, once-patented GS preparation marketed by Rotta (first marketed by Enzymatic Therapy in North America, now marketed by Rotta as DONA™), including two multi-year studies and some data suggesting that the sulfate moiety is indeed of import to cartilage biology.
Another strategy is to improve the method of production to the extent of completely disrupting the existing processing technology(ies). This line is being pursued by at least two large EU-based fine chemical manufacturers with coenzyme Q10 (CoQ10), one through license of a patent suite (US 6545184 and a continuation; EP1328654; and WO 0214530), which employs a facile, cost-favorable chemical synthesis and promises a precipitous fall in production costs relative to those marking the Japanese CoQ10 “cartel”. Like GAIT, a potentially pivotal trial is underway, examining the effects of ultra high dose Q10 (up to 2400 mg/day) in Parkinson’s disease patients, based upon two pilot studies and one showing that 2400 mg/day dosing achieved blood concentrations equal to 3000 mg/day (Exp Neurol, 2004). The industrial-academic constellation comprised of Enzymatic Therapy/Vitaline, the investigators and inventors at UC San Diego, UC Santa Barbara, and Columbia University, and the yet unnamed EU-based fine chemicals manufacturers may, too, teach an old ingredient a new trick and send it on a meteoric rise through hoops long believed unconquerable.NW