1 one year post-exclusivity adverse event review: insulin aspart recombinant pediatric advisory...
TRANSCRIPT
![Page 1: 1 One Year Post-Exclusivity Adverse Event Review: Insulin Aspart Recombinant Pediatric Advisory Committee Meeting November 16, 2006 Hari Cheryl Sachs,](https://reader036.vdocuments.us/reader036/viewer/2022082712/56649f435503460f94c62d91/html5/thumbnails/1.jpg)
1
One Year Post-Exclusivity Adverse Event Review:
Insulin Aspart Recombinant
Pediatric Advisory Committee Meeting November 16, 2006
Hari Cheryl Sachs, MD, FAAPMedical OfficerPediatric and Maternal Health StaffOffice of New DrugsCenter for Drug Evaluation and Research Food and Drug Administration
![Page 2: 1 One Year Post-Exclusivity Adverse Event Review: Insulin Aspart Recombinant Pediatric Advisory Committee Meeting November 16, 2006 Hari Cheryl Sachs,](https://reader036.vdocuments.us/reader036/viewer/2022082712/56649f435503460f94c62d91/html5/thumbnails/2.jpg)
2
Background Drug Information • Drug: NovoLog® (insulin aspart recombinant)• Therapeutic Category: human insulin analog• Sponsor: Novo Nordisk Inc• Original Market Approval: June 7, 2000• Pediatric Exclusivity Granted: May 24, 2005• Mechanism of action: regulation of glucose
metabolism – Binds to insulin receptors on muscle and fat– Facilitates cellular uptake of glucose– Inhibits output of glucose from liver
![Page 3: 1 One Year Post-Exclusivity Adverse Event Review: Insulin Aspart Recombinant Pediatric Advisory Committee Meeting November 16, 2006 Hari Cheryl Sachs,](https://reader036.vdocuments.us/reader036/viewer/2022082712/56649f435503460f94c62d91/html5/thumbnails/3.jpg)
3
Background Drug Information
• Indication: treatment of patients with diabetes mellitus, for the control of hyperglycemia– Normally with regimen of intermediate or long-acting
insulin– May be infused via external insulin pumps– May be used intravenously under medical supervision
• Dosage:– Individualized, immediately prior to a meal
![Page 4: 1 One Year Post-Exclusivity Adverse Event Review: Insulin Aspart Recombinant Pediatric Advisory Committee Meeting November 16, 2006 Hari Cheryl Sachs,](https://reader036.vdocuments.us/reader036/viewer/2022082712/56649f435503460f94c62d91/html5/thumbnails/4.jpg)
4
Drug Use Trends (Outpatient Settings): Insulin Aspart Recombinant
• Dispensed prescriptions for NovoLog have been increasing (June 2004 to May 2006)1
– Total NovoLog® and NovoLog® Mix 70/30 prescriptions increased by estimated 29% (~ 2.4 to 3.4 million)1
– Relative increase in pediatric patient count: 22% (~47,000 to 57,000)2
• Pediatric patients accounted for ~13% of prescriptions2
• Majority of pediatric NovoLog® prescriptions to patients ages 12-16 years1
1Verispan LLC, Vector One National, Jun 2003 to May 2006, Data extracted Jul 20062Verispan LLC, Vector One National: Total Patient Tracker, Data Extracted 7/2006 Excludes NovoLog® Mix 70/30
![Page 5: 1 One Year Post-Exclusivity Adverse Event Review: Insulin Aspart Recombinant Pediatric Advisory Committee Meeting November 16, 2006 Hari Cheryl Sachs,](https://reader036.vdocuments.us/reader036/viewer/2022082712/56649f435503460f94c62d91/html5/thumbnails/5.jpg)
5
Pediatric Exclusivity Labeling changes: Insulin Aspart Recombinant
• Indicated for use in pediatric patients• Pk and clinical studies described, including those in
children ages 2 to 6 years• Glycemic control and adverse events, particularly
hypoglycemia comparable to regular insulin
![Page 6: 1 One Year Post-Exclusivity Adverse Event Review: Insulin Aspart Recombinant Pediatric Advisory Committee Meeting November 16, 2006 Hari Cheryl Sachs,](https://reader036.vdocuments.us/reader036/viewer/2022082712/56649f435503460f94c62d91/html5/thumbnails/6.jpg)
6
Adverse Event Reports since Market Approval (June 2000): Insulin Aspart
All reports (US) Serious (US) Death (US)
All Ages* 1338 (1056) 616 (341) 36 (8)
Adults (> 17) 1051 (828) 491 (275) 30 (8)
Pediatrics (0-16) 154 (117) 72 (35) 5 (0)
*may include duplicates and unknown ages
Serious outcomes per regulatory definition include death, hospitalization, life-threatening, disability, congenital anomaly, requiring intervention, and other
![Page 7: 1 One Year Post-Exclusivity Adverse Event Review: Insulin Aspart Recombinant Pediatric Advisory Committee Meeting November 16, 2006 Hari Cheryl Sachs,](https://reader036.vdocuments.us/reader036/viewer/2022082712/56649f435503460f94c62d91/html5/thumbnails/7.jpg)
7
Fatal Serious AE since approval: Insulin Aspart (n= 4, unduplicated)
Infants born to participants in post-marketing clinical trial in pregnant women with diabetes:
• 4 month old female with truncus arteriosus communis
• 4 day old male with hypoxic ischemic encephalopathy and seizures
Direct exposures
• 14 year old male with type I DM and remote history of asthma found dead in bed, treated for 4-5 months with insulin detemir and aspart; post mortem: “consistent with acute asthma attack, although patient had not had attack in 8 years.”
• 9 year old male with type 2 DM on insulin glargine for 6 months and aspart for unknown period, died, “possible alcohol overdose”
Underlined events are not specifically labeled
![Page 8: 1 One Year Post-Exclusivity Adverse Event Review: Insulin Aspart Recombinant Pediatric Advisory Committee Meeting November 16, 2006 Hari Cheryl Sachs,](https://reader036.vdocuments.us/reader036/viewer/2022082712/56649f435503460f94c62d91/html5/thumbnails/8.jpg)
8
Adverse Event Reports One Year Post Exclusivity Period: Insulin Aspart
Raw counts* All reports (US) Serious (US) Death (US)
All ages 284 (169) 249 (135) 15 (1)
Adults (> 17) 230 (135) 202 (108) 12 (1)
Pediatrics (0-16) 28 (18) 24 (14) 3 (0)
* may include duplicates and unknown ages
![Page 9: 1 One Year Post-Exclusivity Adverse Event Review: Insulin Aspart Recombinant Pediatric Advisory Committee Meeting November 16, 2006 Hari Cheryl Sachs,](https://reader036.vdocuments.us/reader036/viewer/2022082712/56649f435503460f94c62d91/html5/thumbnails/9.jpg)
9
Adverse Event Reports during One-Year Post Exclusivity Period: Unlabeled Serious Non-fatal cases:
Insulin Aspart. In utero exposure (n =4)
– Newborn with neonatal hypoglycemia and ankyloglossia, first trimester exposure insulin lispro, regular insulin, NovoLog®
– 37 week with urinary retention, neonatal asphyxia, and hypoxic-ischemic lesion of the central nervous system, first trimester exposure multiple drugs
– Neonate with dysmorphy of the right frontal lobe, increased frontal subarachnoid space, and assymetry of lateral ventricle
– 32 week preterm with neonatal hypoglycemia (blood glucose 24 mg/dl)
Underlined events are unlabeled
![Page 10: 1 One Year Post-Exclusivity Adverse Event Review: Insulin Aspart Recombinant Pediatric Advisory Committee Meeting November 16, 2006 Hari Cheryl Sachs,](https://reader036.vdocuments.us/reader036/viewer/2022082712/56649f435503460f94c62d91/html5/thumbnails/10.jpg)
10
Summary: Insulin Aspart• Labeling updated after exclusivity studies
– Treatment of type I DM > 2 years – Most frequent AE is hypoglycemia
• During post exclusivity period– Although AEs related to in utero exposure observed, no
pattern– No new pediatric AEs identified
• This completes the one-year post-exclusivity AE reporting as mandated by BPCA.
• The FDA recommends routine monitoring of insulin aspart recombinant for AEs in all populations.
• Does the Advisory Committee concur?
![Page 11: 1 One Year Post-Exclusivity Adverse Event Review: Insulin Aspart Recombinant Pediatric Advisory Committee Meeting November 16, 2006 Hari Cheryl Sachs,](https://reader036.vdocuments.us/reader036/viewer/2022082712/56649f435503460f94c62d91/html5/thumbnails/11.jpg)
11
Acknowledgements
OSE
Andrea Feight
Lanh Green
Solomon Iyasu
Rosemary Johann-Liang
David Moeny
Joslyn Swann
DMEP
David Orloff
Joanna Zawadzki
PMHSLisa MathisKristin PhucasJean Temeck