Drug Pipeline

A retrospective cohort study published in the journal Stroke demonstrated an increased risk of stroke among users of rofecoxib and valdecoxib but not among users of other nonsteroidal anti-inflammatory drugs (NSAIDs).

The purpose of this drug use evaluation was to report potentially inappropriate medication use, as defined by the full Beers criteria.

Alogliptin is a highly selective DPP-IV inhibitor under investigation for the treatment of type 2 diabetes. An NDA for alogliptin was submitted in January 2008, and a response from FDA is expected in the fourth quarter of this year.

Generic drugs approved by FDA (through September 2008) including nisoldipine extended-release tablets and divalproex delayed-release tablets

New indication: Tenofovir (Viread), an antiviral agent, was approved on August 13, 2008, for the treatment of chronic hepatitis B in adults.

FDA has launched the Sentinel Initiative to expand and improve medical product risk detection and evaluation. Instead of relying on passive, voluntary adverse event (AE) reports sent to FDA by physicians and pharmacists, the agency would be able to detect safety signals much more quickly through links to health information databases containing information about millions of patients.

Two randomized, double-blind, phase 3 clinical trials demonstrated that raltegravir plus optimized background therapy was more effective than optimized background therapy alone in suppressing resistant HIV-1.

In a nested, case-control study published in the Archives of General Psychiatry, investigators observed that the use of selective serotonin-reuptake inhibitors (SSRIs) increased the risk of upper gastrointestinal (GI) tract bleeding; this increased risk was also observed with the serotonin and norepinephrine reuptake inhibitor (SNRI) venlafaxine. This risk may be increased when the agents are used concomitantly with nonsteroidal anti-inflammatory drugs (NSAIDs) and decreased when used concomitantly with acid-suppressing agents.

The first phase of a double-blind, randomized, parallel-group, multicenter, outpatient study demonstrated that treatment with the combination of etanercept and methotrexate was more effective in inducing both clinical remission and radiographic nonprogression than methotrexate alone in patients with early moderate-to-severe rheumatoid arthritis (RA).

A recent multinational, randomized, double-blind, placebo-controlled clinical trial demonstrated that administration of aliskiren provides additional renal protection to patients with hypertension, type 2 diabetes mellitus, and nephropathy who are already receiving optimal antihypertensive therapy and renal protective therapy with the angiotensin receptor blocker (ARB) losartan.

Among the new data presented at the 68th Scientific Sessions of the ADA were the results of phase 3 trials of the investigational agents liraglutide, ABT-335, saxagliptin, and alogliptin.

Tocilizumab, an investigational agent for the treatment of moderate-to-severe rheumatoid arthritis, is a humanized anti-IL-6 receptor monoclonal antibody. Because tocilizumab contains a mouse monoclonal antibody grafted onto human immunoglobulin, the grafted antibody is less antigenic and has a longer half-life than the mouse antibody. When administered, tocilizumab inhibits IL-6 activity by competing for both the membrane-bound and soluble types of IL-6 receptors, thus eliminating IL-6 transduction into the cell.

In the Antiarrhythmic Trial with Dronedarone in Moderate to Severe CHF Evaluating Morbidity Decrease (ANDROMEDA) investigators observed that dronedarone, an anti-arrhythmic agent related to amiodarone, was associated with increased mortality in patients who were hospitalized for symptomatic heart failure (HF) (New York Heart Association [NYHA] class II, III, or IV) and left ventricular systolic dysfunction.

New indication: Duloxetine (Cymbalta), an SSNRI, was approved on June 13, 2008, for the management of fibromyalgia

Generic drugs approved by FDA (through August 2008) including risperidone tablets.

New indication: Bortezomib (Velcade), an antineoplastic agent, was approved on June 20, 2008, for the initial treatment of multiple myeloma.

The US orphan drug program has demonstrated that economic incentives and regulatory flexibility can spur development of treatments for small patient populations. Since enactment of the Orphan Drug Act (ODA) in 1983, FDA has approved >300 medicines for approximately 12 million patients around the world. However, there are approximately 6,000 to 8,000 rare diseases, so “we still have a very long way to go,” commented Janet Woodcock, director of the Center for Drug Evaluation and Research (CDER), at a May conference commemorating ODA’s 25th anniversary, which was sponsored by the Drug Information Association (DIA).

Hospital-acquired pneumonia (HAP) is a frequently occurring complication of endotracheal intubation and hospitalization that is associated with a significant increase in morbidity, mortality, and cost of care.

Tolvaptan is an oral selective vasopressin V2 receptor antagonist that works to produce aquaresis (water diuresis without electrolyte excretion) by blocking the effects of AVP. This effect makes tolvaptan a viable treatment option for patients with acute decompensated heart failure (ADHF) and hyponatremia.

Generic drugs approved by FDA (through July 2008) including fluoxetine capsules and calcipotriene topical solution.

New indication: Atomoxetine (Strattera), a selective norepinephrine reuptake inhibitor, was approved on May 7, 2008, for the maintenance treatment of ADHD in children and adolescents.

NME: Alvimopan (Entereg), a peripherally acting mu-opioid receptor antagonist, was approved on May 20, 2008, to accelerate the time to upper and lower GI recovery after partial large or small bowel resection surgery with primary anastomosis.

Epoetin alfa in 1993 and darbepoetin alfa in 2002 were approved for the management of chemotherapy-induced anemia (CIA).

Healthcare reform is a high-profile issue in the presidential election campaign, and drug access has become a central theme in the debate. Both Democratic and Republican candidates have rolled out healthcare reform plans that promise to cover the uninsured while also providing tax breaks and other incentives to help individuals obtain health insurance.

In June 2007, FDA approved an Electronic Medication Management Assistant (EMMA) device and electronic medication administration record (eMAR) to help combat problems involving drug identification and dosing.

An investigational 500-mcg dose of interferon beta-1b demonstrated no advantage compared with the approved 250-mcg dose of interferon beta-1b or with glatiramer 20 mg in reducing relapse risk in patients with early relapsing-remitting multiple sclerosis (RRMS), said Paul O'Connor, MD, MS Program Director, St. Michael's Hospital, the University of Toronto, at the 60th Annual Meeting of the American Academy of Neurology, Chicago.

Lacosamide safely decreases pain scores in patients with painful diabetic neuropathy, according to a pooled efficacy and safety analysis presented at the 60th Annual Meeting of the American Academy of Neurology, Chicago.

Glatiramer represents a new option for delaying conversion of clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS), according to the results of a new study known as PRECISE, presented at the 60th Annual Meeting of the American Academy of Neurology, Chicago.

Iloperidone, a new-generation atypical antipsychotic, is currently under investigation for the treatment of schizophrenia. In 4 separate phase 3 trials, iloperidone has demonstrated efficacy in treating schizophrenia, with total Positive and Negative Symptom Scale (PANSS) scores decreasing by a range of 8 to 14 points depending on the iloperidone dose.

Generic drugs approved by FDA (through June 2008) including epoprostenol for injection, ropinirole, donepezil, and drospirenone/ethinyl estradiol.