Roche is Under Pressure Over Its Antiviral Drug Tamiflu
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Roche, the manufacturer of oseltamivir (Tamiflu), has found itself struggling to keep up with demand for its antiviral drug in the face of a possible avian flu epidemic. Countries worldwide are stockpiling the drug, which has resulted in hundreds of millions of dollars in sales for the company. But now, Roche is facing pressure from the worldwide community to allow generic production of Tamiflu. Taiwanese officials have indicated that they could begin mass production relatively quickly, and UN Secretary-General Kofi Annan has urged licensing of the drug to generic companies. An Indian drug company has announced that it will begin production of the drug, despite the risk of patent infringement lawsuits. Cipla, based in Bombay, India’s third largest drug company, will soon begin production. Meanwhile Roche, which sells Tamiflu for $60 per treatment course, is working to expand production, but has stated that the process is too complex and time-consuming for generic houses to manufacture. Officials from Cipla report that they have reverse engineered the drug and could distribute generic oseltamivir as early as January 2006. They also state that they will sell the drug for "a humanitarian price." Tamiflu is approved for treating both influenza A and B, and for prophylaxis of both viruses. There have been several recent reports that avian influenza A may be showing some resistance to Tamiflu, however, these were based on a single report from Vietnam of a H5N1 virus that was partially resistant to the drug, and not on any evidence of widespread resistance.
ACE Inhibitors or ARBs for Prediabetics?
ACE inhibitors and angiotensin receptor blockers (ARBs) are not only cardio and renal protective for diabetics, the drugs may help prevent the onset of diabetes and those at risk. Researchers from the Mid America Heart Institute conducted a meta-analysis of 12 randomized, controlled clinical trials of ACE inhibitors or ARBs. Over 116,000 patients were entered into the trial, including over 72,000 who did not have diabetes at baseline. ACE inhibitors were associated with a reduction in the incidence of newly diagnosed diabetes of 27%, while ARBs were associated with a 23% reduction. The authors conclude that an ACE inhibitor or ARB should be considered in patients with prediabetic conditions such as metabolic syndrome, hypertension, impaired fasting glucose, family history of diabetes, obesity, congestive heart failure, or coronary heart disease (Abuissa H, et al. Angiotensin-Converting Enzyme Inhibitors or Angiotensin Receptor Blockers for Prevention of Type 2 Diabetes A Meta-Analysis of Randomized Clinical Trials. J Am Coll Cardiol. 2005;46:821-826).
Xigris is Approved for Severe Sepsis
Drotrecogin alfa (DrotAA trade name Xigris) is approved for the treatment of adults with severe sepsis and a high risk of death. A recent study suggests that the drug is not effective for patients with sepsis and a low risk of death, as determined by an Adult Physiology and Chronic Health Evaluation (APACHE II) score of < 25 or single organ failure. The study enrolled 2640 patients who met criteria of sepsis and the risk of death (1297 in the placebo group and 1316 in the DrotAA group). The study was stopped early because of a low likelihood of making the prospectively defined objective of demonstrating a significant reduction in the 28-day mortality rate with use of the drug. There were no statistically significant differences between placebo and DrotAA in 28-day mortality (17.0% placebo, 18.5% DrotAA; P = 0.34;RR 1.08; 95% CI, 0.92-1.28) or in in-hospital mortality (20.5% vs 20.6%; P = 0.98; RR, 1.0; 95% CI, 0.86-1.16). The rate of serious bleeding was greater in the DrotAA group than in the placebo group, both during the infusion (2.4% vs 1.2%,P = 0.02) and the 28-day study period (3.9% vs 2.2%, P = 0 .01). The authors conclude that the lack of benefit coupled with the increase risk of serious bleeding suggest that DrotAA should not be used in patients with severe sepsis who are low risk for death (N Engl J Med. 2005;353:1332-1341). An accompanying editorial suggests that DrotAA should still be considered for severe sepsis with an APACHE II score of > 25, but this current study refines the parameters for use in less sick patients (Parrillo JE. Severe Sepsis and Therapy with Activated Protein C. N Engl J Med. 2005;353:1398-1400).
ACE Inhibitors Inhibiting Aortic Valve Stenosis?
Conventional wisdom has suggested that ACE inhibitors should be used with caution or not all in patients with aortic valve stenosis. A new study challenges that assumption with the review of 20 patients with an average age of 73, a mean valve area of 0.7 cm², and left ventricular ejection fraction of 45%. Patients underwent clinical evaluations, echocardiograms, and exercise echocardiography with and without ACE inhibitor therapy. During therapy, there was no change in patients’ subjective functional class. The patients had a lower systolic blood pressure with ACE inhibitors (140 mm Hg vs 159 mm Hg, P = 0.02), a higher mean pressure gradient (34 mm Hg vs 28 mm Hg, P = 0.037), and a higher left ventricular stroke work loss of apparent 19% vs 14%, P = 0 .009). Other baseline functional and hemodynamic parameters were unmodified. The authors conclude that with aortic stenosis, the afterload relief caused by ACE inhibitors is blunted by a parallel increase in the pressure gradient, and that ACE inhibitors favorably affect stress hemodynamic function in most hypertensive patients with aortic stenosis (Jimenez-Candil J, et al. Effects of Angiotensin Converting Enzyme Inhibitors in Hypertensive Patients with Aortic Valve Stenosis: A Drug Withdrawal Study. Heart. 2005;91:1311-1318).
FDA Actions
The FDA has approved Schering’s estradiol/drospirenone combination for hormone replacement therapy in women with moderate- to-severe menopausal symptoms. The approval has taken several years due to controversy with HRT following the Women’s Health Initiative study that was published in 2002. The drug is unique in that it combines estradiol with drospirenone, a spironolactone analogue which serves as a mild diuretic. Because of the antialdosterone effects of the drug and the risk of elevating potassium levels, it should not be used in women with liver, kidney, or adrenal disease. Schering will market estradiol/drospirenone as Angeliq.
The FDA has issued an alert regarding 5 cases of Guillain-Barré Syndrome (GBS) associated with the use of Meningococcal Conjugate Vaccine A, C, Y, and W135 (Menactra, Sanofi Pasteur). The agency is investigating whether the vaccine is implicated in these cases or whether it is coincidence. All 5 cases occurred in 17 or 18 year-old individuals, 2 to 4 weeks after they received the vaccine. They all lived in Ohio, New York, Pennsylvania, or New Jersey. There is a background rate of the GSB, and 5 cases among the 2.5 million patients that have been vaccinated could potentially be by chance. The FDA is making this announcement to seek out other cases that may have gone unreported. All 5 patients are reported to be recovering or to be fully recovered. Menactra is approved for prevention of meningococcal disease in adolescents and adults age 11 to 55 years. It is commonly given to adolescents prior to starting high school or college.
This supplement was written by William T. Elliott, MD, FACP, Chair, Formulary Committee, Kaiser Permanente, California Division; Assistant Clinical Professor of Medicine, University of California-San Francisco. In order to reveal any potential bias in this publication, we disclose that Dr. Elliott reports no consultant, stockholder, speaker’s bureau, research, or other financial relationships with companies having ties to this field of study. Questions and comments, call: (404) 262-5416. E-mail: [email protected].
Roche is Under Pressure Over Its Antiviral Drug Tamiflu; ACE Inhibitors or ARBs for Prediabetics?; Xigris is Approved for Severe Sepsis; ACE Inhibitors Inhibiting Aortic Valve Stenosis?; FDA ActionsYou have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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