News from the FDANews from the FDAApprovals through June 2003Approvals through June 2003

Emend (aprepitant)Emend (aprepitant)

March 26, 2003 Approved for use in combination with other anti-nausea

and anti-vomiting drugs for delayed N&V associated with initial and repeat courses of chemotherapy.

Novel site of action: NK1 receptor PK:

Expected interactions with warfarin (CYP2C9) and OC. Metabolized by CYP3A4 (main) and CYP1A2 (minor)

Studies: 2 trials with > 1000 patients Manufactured by Merck

Website: http://www.emend.com

West Nile ELISA testWest Nile ELISA test

July 9, 2003 Test approved as aid in diagnosis of WNV in patients with

clinical symptoms consistent with viral encephalitis/meningitis.

Sensitivity 90 - 99% Specific testing needed for confirmation.

Cypher Cypher (sirolimus-eluting coronary stent)(sirolimus-eluting coronary stent)

April 24, 2003 Approved for angioplasty procedures to open clogged coronary

arteries. Review based on laboratory and animal tests and 2 clinical trials.

SIRIUS Study (US Study)• N = 1058, Cypher vs uncoated stent

• At 9-months treated group with less repeat procedures: 4.2 vs 16.8%

• Lower restenosis 8.9 vs 36.3%

• Combined endpoints 8.8 vs 21%

RAVEL Study (outside US) Cordis (J&J) Website: http://www.cypherusa.com

Prilosec OTCPrilosec OTC

June 20, 2003 Approved for “frequent heartburn”. Formulation: 20 mg delayed release

Taken before meals once daily for 14 days Labeled for a single 2-week course not more often than every 4

months. Drug interactions to discuss with patients:

Based on interaction with CYP2C19 and CYP3A4 Warfarin, chlorazepate, quinolone antibiotics, ketoconazole,

propranolol, quinidine, ticlopidine, phenytoin, methotrexate. Consumer website: http://www.priloseconline.com/

Fabrazyme Fabrazyme (agalsidase beta)(agalsidase beta)

April 24, 2003 Approved for treatment of Fabry Disease

Orphan drug Deficiency in alpha-galactosidase A Agalsidase is human form of enzyme produced by recombinant

DNA technology Approval under accelerated mechanism based on blood vessel

biopsies of treated patients Genzyme Co. www.genzyme.com

Administered IV 1mg/kg every 2 weeks Infusion reactions are frequent and can be severe.

• Replagal is alpha-galactosidase A by Transkaryotic Therapies Inc

Agalsidase alphaAgalsidase alpha

Compare: use Micromedex

Micromedex on THR or Caregate

IressaIressa(genfitinib)(genfitinib)

May 5, 2003 Approved as single agent treatment for advanced NSCLC Accelerated approval Mechanism of action not known

Developed to block stimulatory signals in cancer cells mediated by tyrosine kinase including EGFR

Large studies showed no benefit Subset analysis suggested selected benefit.

“Third-line” drug for patients with no other options Studies are on-going. AstraZeneca Website: http://www.iressa-us.com/

VelcadeVelcade (bortezomib)(bortezomib)

May 13, 2003 Approved for treatment of multiple myeloma under

accelerated approval protocol. Approved for patients who relapse after 2 prior treatments

or are resistant to last treatment. Study: 202 patients (188 evaluated).

28% response rate. Smaller study with similar results (54)

ADE: Nausea, fatigue, diarrhea, headache, neutropenia, anemia, fever, peripheral neuropathy.

Velcade, cont.Velcade, cont.

Marketed by Millennium Pharmaceuticals Millineum pharmaceuticals website

Boronic acid dipeptide

Bortezomib, cont’d.Bortezomib, cont’d.

Specific/selective inhibitor of 26S proteasome Multicatalytic protease in all eukaryotic cells Degrades proteins that have been conjugated to ubiquitin Major mechanism for orderly intracellular protein degradation

(80%) regulatory proteins: cellular integrity, cell-cycle control, cellular

apoptosis, transcription factor activation, and tumor growth Exerts a dysregulating effect on these regulatory proteins,

resulting in disruption of cell proliferation and apoptosis.

FluMistFluMist(influenza virus vaccine, live)(influenza virus vaccine, live)

June 17, 2003 First nasally administered vaccine in US First live influenza virus vaccine approved in US Study:

20,228 patients including 10,000 children. Efficacy of 87% (pediatric) For patients > 50 yo the “safety and efficacy has not been established”.

Not for use in people with chronic underlying conditions that may predispose them to severe flu. Use injected vaccine.

Made by Medimmune Website http://www.medimmune.com/