News from the FDA Approvals through June 2003

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News from the FDAApprovals through June 2003
Pharmacophilic minutes
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Emend (aprepitant)

• March 26, 2003
• Approved for use in combination with other
  anti-nausea and anti-vomiting drugs for delayed
  NV 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 gt 1000 patients
• Manufactured by Merck
• Website http//www.emend.com

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West 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.

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Cypher (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 (JJ)
• Website http//www.cypherusa.com

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Prilosec 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/

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Fabrazyme (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

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Agalsidase alpha

• Compare use Micromedex
• Micromedex on THR or Caregate

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Iressa(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/

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Velcade (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.

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Velcade, cont.

• Marketed by Millennium Pharmaceuticals
• Millineum pharmaceuticals website
• Boronic acid dipeptide

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Bortezomib, contd.

• 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.

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FluMist(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 gt 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/