Drug Pipeline

Enfuvirtide is the first drug to be approved in a new class of anti-HIV drugs known as fusion inhibitors (see "Focus On... Enfuvirtide"). The drug interferes with the entry of HIV-1 into immune cells by inhibiting the fusion of viral and cellular membranes. This occurs when enfuvirtide prevents conformational changes required for the fusion of viral and cellular membranes by binding to the first heptad-repeat (HR1) in the gp41 subunit of the viral envelope glycoprotein. Enfuvirtide, in combination with other antiretroviral agents, is intended for the treatment of HIV-1 infection in treatment-experienced patients with evidence of HIV-1 replication despite ongoing antiretroviral therapy.

Two options are available for patients requiring treatment for arthritis who are at risk for ulcer disease: nonsteroidal anti-inflammatory drugs (NSAIDs) that are selective for cyclooxygenase-2 (COX-2) or the combination of a non-selective NSAID with a proton-pump inhibitor. A recent study of representative members from these therapeutic classes has offered findings that the two alternatives are statistically similar in their efficacy with respect to the prevention of recurrent ulcer bleeding.Celecoxib, a COX-2-selective NSAID, was given to 144 patients through random assignment. Another group of patients (N=143) were randomly assigned to receive a combination of diclofenac (a nonselective NSAID) plus omeprazole (a proton-pump inhibitor) during the 6-month trial.

Corticosteroid therapy is an effective treatment for asthma sufferers, but the use of systemic corticosteroids is known to increase the risk of osteoporotic fractures. A recent study published in the Journal of Allergy and Clinical Immunology suggests that moderate doses of inhaled corticosteroids (ICs) carry less risk than traditional oral corticosteroid (OC) therapy with respect to reduction of bone mineral density (BMD) in postmenopausal women. This assertion is based on the premise that the lowest daily dose of IC sufficient to control the patient's asthma is used.

Enfuvirtide (Fuzeon, Roche/Trimeris) is the first member of a unique class of antiretrovirals known as the fusion inhibitors to gain FDA approval for the treatment of human immunodeficiency virus type-1 (HIV-1) infection. Enfuvirtide is indicated for use in combination with other antiretroviral agents in the treatment of HIV-1 infection in treatment-experienced patients with evidence of HIV-1 replication despite ongoing antiretroviral therapy. Phase 3 trials demonstrated that adding enfuvirtide 90 mg twice daily to an optimized background regimen chosen with genotypic and phenotypic resistance testing improved the surrogate end points of HIV ribonucleic acid (RNA) levels, CD4 cell counts, and the proportion of patients reaching clinically undetectable HIV RNA levels (<400 and <50 copies/mL) through 24 weeks. Enfuvirtide?s efficacy in treatment-experienced patients when added to an optimized background regimen makes it a promising choice for salvage therapy. Further studies will be required to support enfuvirtide?s use in treatment-naïve patients.

New Indication: SSRI approved for social anxiety disorder

Selective serotonin reuptake inhibitors (SSRIs) experienced increased usage in the 1990s due to their low toxicity and minimal adverse effects. Throughout this period, several clinical reports indicated a link between the use of SSRIs and various bleeding disorders. A recent study published in the Archives of Internal Medicine found a distinct correlation between the use of SSRIs and upper gastrointestinal (GI) tract bleeding. The population-based cohort study was conducted within the 490,000 residents of a northern Denmark county over a five-year period.

First SNRI approved for social anxiety disorder

New indications: Leukotriene blocker approved for treatment of seasonal allergic rhinitis

NME: First biologic treatment approved for psoriasis

NME: New triptan approved for acute migraine treatment

Vardenafil (Levitra, Bayer AG/GlaxoSmithKline) is a selective inhibitor of phosphodiesterase 5 (PDE5) currently under review by FDA for the treatment of erectile dysfunction (ED). If approved, vardenafil will become the third PDE5 inhibitor to be marketed in the United States and the fourth oral agent approved for the treatment of ED. Vardenafil has been studied in subjects of various ages (<45 and >65 years of age), with different etiologies and different baseline severity of ED. Studies evaluating vardenafil have determined it to be safe and effective at doses of 5 mg to 40 mg, including subjects with diabetes mellitus and subjects who have undergone radical prostatectomy. Vardenafil has a pharmacokinetic profile similar to that of sildenafil (Viagra, Pfizer). The drug appears to be well tolerated. In clinical trials, headache, dyspepsia, and flushing were the most common adverse effects reported by subjects taking vardenafil. No adverse hemodynamic or visual effects have been reported during clinical trials of vardenafil; however, further investigation, including post-marketing surveillance, will be required. Further research and clinical experience with the newer PDE5 inhibitors (vardenafil and tadalafil [Cialis, Lilly/ICOS]) will be needed before their roles in the treatment of ED can be determined.

Pulmonary arterial hypertension (PAH) is a progressive, debilitating disorder associated with poor quality of life and shortened life span. For many years, medical therapy consisted of calcium channel blockers, warfarin, supplemental oxygen, and digitalis glycosides. A better understanding of the pathophysiology of PAH has led to the recent development of effective treatments for this disorder. Therapeutic agents target the pathophysiologic mechanisms of PAH: pulmonary vasoconstriction, pulmonary vascular remodeling, and in situ thrombosis. With better understanding of the pathogenesis of PAH, recent advances in pharmacotherapy have been introduced for the treatment of PAH. Data are presented on efficacy and safety of newer approved and investigational agents: prostacyclin analogues, oral endothelin antagonists, and phosphodiesterase 5 inhibitors.

The central healthcare initiative in the administration's $2.2 trillion budget proposal for fiscal year 2004 is to establish a Medicare prescription drug benefit. President George W Bush proposes to spend $6 billion as a "down payment" on a $400 billion/10-year Medicare drug benefit and "modernization" plan.

Treatment strategies from: Vincent T. Andriole, MD, Professor of Medicine, Yale University School of Medicine Attending Physician, Yale-New Haven Hospital, New Haven, Connecticut

Antidepressant now approved for use in pediatric patients

Glaxo-SmithKline (GSK) has advised prescribers of salmeterol (Serevent) about rare, but potentially serious, respiratory adverse events in patients with asthma.

New formulation: Drug increases tear production in patients with chronic dry eye due to ocular inflammation

The recent selection of Sen Bill Frist (R-Tenn), MD, to lead Senate Republicans has moved healthcare policy up the priority list in the Senate. As a physician, Dr Frist has played a lead role in assessing federal health programs and policies.

NME: New treatment for rheumatoid arthritis

NME: New solution for home-based peritoneal dialysis

Atomoxetine, a norepinephrine reuptake inhibitor, is the first nonstimulant agent approved for the treatment of ADHD (Strattera, Lilly). It has been approved for use in pediatric and adult patients. Atomoxetine improves ADHD symptom severity versus placebo, as evaluated by the ADHD Rating Scale (ADHD RS), and its efficacy appears comparable to immediate-release methylphenidate. Atomoxetine requires dosage titration and may be administered once or twice daily. Common side effects seen in both pediatric and adult patients include nausea, decreased appetite, and dizziness. Dosage adjustments are necessary for patients receiving atomoxetine and cytochrome P450 2D6 inhibitors. Based on average wholesale price (AWP), atomoxetine is more costly than existing ADHD therapies. Atomoxetine provides an alternative ADHD therapy for patients who may fail or cannot tolerate conventional treatments.

Intraabdominal infection was first thoroughly described by Hippocrates. Centuries later, despite advances in surgical and supportive therapies, this disease state continues to be associated with significant morbidity and mortality. This article reviews the literature on intraabdominal infections. It describes the pathophysiology, classification, and etiology of intraabdominal infections, focusing primarily on secondary peritonitis. The bacteriology of the gastrointestinal tract in both the normal and infected host is reviewed. Treatment options, including newly approved antimicrobial agents and agents under clinical investigation, are reviewed.

Direct-to-consumer (DTC) advertising is boosting prescription use, pharmaceutical companies are spending more on DTC ads, and FDA needs to act more quickly to remove false or misleading commercials from the air.

Ann Arbor, Mich-Atorvastatin, especially at higher dosages, may prevent activation of the antiplatelet agent clopidogrel, according to research at the University of Michigan, Ann Arbor.

The American Academy of Family Physicians and the American College of Physicians­American Society of Internal Medicine, with assistance from the American Headache Society, released the migraine treatment guidelines. Migraine headaches affect 18% of women and 6.5% of men in the United States and are a major cause of absenteeism and reduced productivity.