Managed Care - March 2008 - (Page 58) TOMORROW’S MEDICINE Role of phenylalanine henylalanine is one of several amino acids that are critical to normal brain development and function. If the levels of Phe rise, as is the case for this disease, the brain can be irreparably damaged in early infancy. It appears that the amount of damage is related to the absolute levels of phenylalanine. Signs and symptoms include mental retardation, behavioral and social problems, seizures, tremors, hyperactivity, stunted growth, skin rashes, and microcephaly. A musty odor emanates from children afflicted with PKU. The distinctive odor is due to the secretion of phenylpyruvate, a ketone, which is excreted in increased amounts because of a secondary Phe metabolic pathway that converts Phe to phenylpyruvate. PKU affects gray as well as white matter in the brain. Phe crosses the blood-brain barrier via specialized receptors that transport a number of large neutral amino acids. Phe has the greatest affinity for this receptor, and hence as phenylalanine levels increase, it appears that other amino acids, also essential for brain development and function, are prevented from entering the brain. This receptor also appears to transport neurotransmitter precursors such as L-DOPA. The end result of decreased essential amino acids and lack of precursors for neurotransmitters appears to explain the multiple central nervous system manifestations of PKU. P women and nursing mothers or in children under 4 years of age. According to Form 8-K, released on Dec. 13, 2007, the price of Kuvan will be 29 cents per mg, which amounts to an average annual cost of $57,000 per patient. Managed care implications The development of Kuvan raises some interesting questions for managed care decisionmakers. Should managed care restrict payment to just certain ages (study participants were ages 4–48)? Given the historical treatment with diet alone, should managed care require a supervised diet before initiating this therapy? Should patients who respond to an aggressive diet but cannot maintain compliance be denied coverage? Should long-term outcomes be proven for adults requesting therapy, as no long-term outcomes data were presented in the studies? Should a compliance program be initiated to ensure that best outcomes are maintained? Given that the endpoints did not include mental outcomes, what does a 30-percent reduction mean to the patient? Although Kuvan does not cure PKU, and does not result in improvement of all patients with PKU, it does demonstrate how advances in the understanding of human biochemistry and genetics can lead to a successful approach to treating previously untreatable diseases. Although this product does not overcome the need for a strict diet, it does offer a therapeutic option when Phe level cannot be controlled through diet alone. It also underscores the way new developments continue to improve the hope and lives of people affected by genetic disease but add incremental costs to our already burdened payment system. MC The author is a director in the value-based health department at Genentech Inc. During the last three years, before taking the Genentech position, he received honoraria or other financial benefits from: Amgen, Amylin Pharmaceuticals, AstraZeneca, Biogen Idec, Centocor, Galderma, GlaxoSmithKline, Johnson & Johnson, Merck, Novartis, Novo Nordisk, Pfizer, Procter & Gamble, Q-Med, Sanofi-Aventis, Teva Pharmaceuticals Industries, UCB, and Wyeth. The views expressed in Tomorrow’s Medicine are the author’s alone. during the initiation phase to correctly measure response to the drug. In clinical trials, 20 percent to 56 percent of PKU patients responded. Side effects were not significantly different between the treated group and the placebo group in the double-blind, placebo-controlled study. There were slight differences in neutropenia, rhinorrhea, and pharyngolaryngeal pain. Kuvan has not been studied in pregnant ADVERTISING INDEX FOREST LABORATORIES Bystolic 35–42 HEALTH DIALOG Health Plans 5 INSPIRE PHARMACEUTICALS Corporate C4 MERCK & COMPANY Janumet 17–19 SOLVAY PHARMACEUTICALS Corporate 23 TAKEDA PHARMACEUTICALS AMERICA Actos C2–2 58 MANAGED CARE / MARCH 2008
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