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Rapivab - peramivir injection Manufacturer: BioCryst Pharmaceuticals FDA Approval Date: 12/19/2014

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Page 1: Rapivab ™ - peramivir injection Manufacturer: BioCryst Pharmaceuticals FDA Approval Date: 12/19/2014

Rapivab™ - peramivir injection

Manufacturer:

BioCryst Pharmaceuticals

FDA Approval Date: 12/19/2014

Page 2: Rapivab ™ - peramivir injection Manufacturer: BioCryst Pharmaceuticals FDA Approval Date: 12/19/2014

Rapivab™ - peramivir injection

Clinical Application

• Indications:

• Acute, uncomplicated influenza in patients 18 years and older who have been symptomatic for less than 2 days

• Place in therapy:• Rapivab should be used in patients who:

• test positive for the influenza virus• have symptoms for less than 48 hours AND• are unable to tolerate inhaled or PO medication

Page 3: Rapivab ™ - peramivir injection Manufacturer: BioCryst Pharmaceuticals FDA Approval Date: 12/19/2014

Rapivab™ - peramivir injection

Clinical Application

• Contraindications:• NONE

• Warnings/ Precautions:• Serious skin and hypersensitivity

reactions

• Neuropsychiatric events

• Risk of bacterial infections

Page 4: Rapivab ™ - peramivir injection Manufacturer: BioCryst Pharmaceuticals FDA Approval Date: 12/19/2014

Rapivab™ - peramivir injection

Clinical Application

• Pregnancy:• Category C

• Lactation:• Not known if the drug is excreted in

human breast milk

Page 5: Rapivab ™ - peramivir injection Manufacturer: BioCryst Pharmaceuticals FDA Approval Date: 12/19/2014

Rapivab™ - peramivir injection

Drug Facts

• Pharmacology:• An injectable neuraminidase inhibitor for

the influenza virus. Through inhibition of the neuraminidase enzyme, peramivir prevents infected cells from releasing viral particles.

Page 6: Rapivab ™ - peramivir injection Manufacturer: BioCryst Pharmaceuticals FDA Approval Date: 12/19/2014

Rapivab™ - peramivir injection

Drug Facts

• Pharmacokinetics:

A 100% bioavailability

DVd: 12.56 L < 30% protein binding

M Not significantly metabolized

ET1/2: ~20 hourseliminated via the kidney with 90% unchanged

Page 7: Rapivab ™ - peramivir injection Manufacturer: BioCryst Pharmaceuticals FDA Approval Date: 12/19/2014

Rapivab™ - peramivir injection

Drug Interactions

• Drug Interactions – Object Drugs: • Influenza Virus Vaccine (variable %)

Page 8: Rapivab ™ - peramivir injection Manufacturer: BioCryst Pharmaceuticals FDA Approval Date: 12/19/2014

Rapivab™ - peramivir injection

Drug Interactions

• Drug Interactions – Precipitant Drugs: • NONE

Page 9: Rapivab ™ - peramivir injection Manufacturer: BioCryst Pharmaceuticals FDA Approval Date: 12/19/2014

Rapivab™ - peramivir injection

Adverse Effects

Rapivab (peramivir) Placebo

Diarrhea 8% 6%

Alanine Aminotransferase

(> 2.5 x ULN) 3% 2%

Serum Glucose (> 160 mg/dL)

5% 3%

Creatine Phosphokinase (≥ 6.0 x ULN)

4% 2%

Neutrophils (< 1.000 x109 /L)

8% 6%

Page 10: Rapivab ™ - peramivir injection Manufacturer: BioCryst Pharmaceuticals FDA Approval Date: 12/19/2014

Rapivab™ - peramivir injection

Monitoring Parameters

• Efficacy Monitoring:• Resolution of influenza symptoms

(headache, aches/pains, fatigue, cough, sore throat, nasal congestion)

• Toxicity Monitoring:• Neurological abnormalities/abnormal

behavior

• Rash after administration

Page 11: Rapivab ™ - peramivir injection Manufacturer: BioCryst Pharmaceuticals FDA Approval Date: 12/19/2014

Rapivab™ - peramivir injection

Prescription Information

• Dosing: 600mg IV infusion over 15 minutes

• Cost: No information at this time

Page 12: Rapivab ™ - peramivir injection Manufacturer: BioCryst Pharmaceuticals FDA Approval Date: 12/19/2014

Rapivab™ - peramivir injection

Literature Review

• Efficacy and Safety of Intravenous Peramivir for Treatment of Seasonal Influenza Virus Infection

• Purpose: To determine the safety and efficacy of a single administration of peramivir in patients with the influenza virus in the outpatient setting

• Design: Randomized, double-blind, placebo controlled trial

Kohno S et al. AAC. 2010 Nov, 54(11): 4568-4574

Page 13: Rapivab ™ - peramivir injection Manufacturer: BioCryst Pharmaceuticals FDA Approval Date: 12/19/2014

Rapivab™ - peramivir injection

Literature Review

Inclusion Exclusion

20 – 64 year old, previously healthy Respiratory dysfunction/ chronic

respiratory disorder

Onset of influenza symptoms < 48 HConvulsions or other neurological

symptoms

Positive rapid antigen test HIV

Fever > 38o CRenal impairment requiring

hemodialysis

Presence of at least 2 flu symptoms

Treatment with steroids/ other immunosuppressants or anti-

influenza drugs within the previous 7 days

Women who are pregnant

Kohno S et al. AAC. 2010 Nov, 54(11): 4568-4574

Page 14: Rapivab ™ - peramivir injection Manufacturer: BioCryst Pharmaceuticals FDA Approval Date: 12/19/2014

Rapivab™ - peramivir injection

Literature ReviewPeramivir 300mg Peramivir 600mg Placebo

Male 46 [46.5%] 53 [54.6%] 51 [51%]

Age 34.2 33.9 34.4

Symptom Onset

0 – 24 hours 59 [59.6%] 51 [52.6%] 48 [48%]

24 – 48 hours 40 [40.6%] 46 [47.4%] 52 [52%]

Composite symptom score

11.5 11.8 12.0

Body temperature 38.44 38.64 38.50

Influenza virus

A/H1 74 [74.7%] 69 [71.1%] 72 [72%]

A/H3 21 [21.2%] 25 [25.8%] 24 [24%]

A/- 2 [2.0%] 2 [2.1%] 4 [4%]

B 2 [2.0%] 2 [1.0%] 0 [0%]

Kohno S et al. AAC. 2010 Nov, 54(11): 4568-4574

Page 15: Rapivab ™ - peramivir injection Manufacturer: BioCryst Pharmaceuticals FDA Approval Date: 12/19/2014

Rapivab™ - peramivir injection

Literature Review

• Primary Endpoint: time from start of treatment to recovery (all influenza symptoms scores had been 0 or 1 for 21.5 hours)

• Other Endpoints:

• Change in composite symptom scores

• Proportion of afebrile subjects

• Change in influenza titer from baseline

• Time to resume usual activity

• Incidence of influenza related illness

Kohno S et al. AAC. 2010 Nov, 54(11): 4568-4574

Page 16: Rapivab ™ - peramivir injection Manufacturer: BioCryst Pharmaceuticals FDA Approval Date: 12/19/2014

Rapivab™ - peramivir injection

Literature Review

• Statistical Analysis:• Intention to Treat

• 67 subjects needed per group to have 80% power

• Treatment Arms:

• 300 mg peramivir (n=99)• 600 mg peramivir (n=97)• Placebo (n=100)

Kohno S et al. AAC. 2010 Nov, 54(11): 4568-4574

Page 17: Rapivab ™ - peramivir injection Manufacturer: BioCryst Pharmaceuticals FDA Approval Date: 12/19/2014

Rapivab™ - peramivir injection

Literature Review

• Primary Endpoint:

• Rapivab significantly reduced the time to alleviation of influenza symptoms compared to the placebo. • HR: 0.681 (adjusted P value, 0.0092) in the 300 mg

group

• HR: 0.666 (adjusted P value, 0.0092) in the 600 mg group

• Patients reported shorter time in resumption of there usual activities

Kohno S et al. AAC. 2010 Nov, 54(11): 4568-4574

Page 18: Rapivab ™ - peramivir injection Manufacturer: BioCryst Pharmaceuticals FDA Approval Date: 12/19/2014

Rapivab™ - peramivir injection

Literature Review

• Effect of Rapivab on viral shedding:• At baseline viral titers similar in all

groups • At 3 days: virus positive patients were

lower in the treatment arms • 300 mg P: 0.0485, 600 mg P: 0.0003

• At 9 days: virus was not detected in most patients

Kohno S et al. AAC. 2010 Nov, 54(11): 4568-4574

Page 19: Rapivab ™ - peramivir injection Manufacturer: BioCryst Pharmaceuticals FDA Approval Date: 12/19/2014

Rapivab™ - peramivir injection

Literature Review - Results

Population Parameter Peramivir 300 mg Peramivir 600 mg Placebo

Overall NMedian (hr)

HRAdjusted P

9959.1

0.6810.0092

9759.9

0.6660.0092

10081.8

Influenza

A/H1 NMedian (hr)

HRAdjusted P

7452.5

0.7790.145

6962.6

0.8990.5384

7281.4

A/H3 NMedian (hr)

HRAdjusted P

2176.1

0.5420.0556

2550.5

0.3260.0008

2481.0

Symptom duration

0 – 24 hr NMedian (hr)

HRAdjusted P

5957.2

0.6530.0516

5156.1

0.6630.0516

4886.7

24-48 hr NMedian (hr)

HRAdjusted P

4069.1

0.7080.1118

4664.7

0.6940.1118

5270.8

Kohno S et al. AAC. 2010 Nov, 54(11): 4568-4574

Page 20: Rapivab ™ - peramivir injection Manufacturer: BioCryst Pharmaceuticals FDA Approval Date: 12/19/2014

Rapivab™ - peramivir injection Literature Review – Adverse Events

Parameter Rapivab 300 mg Rapivab 600 mg Placebo

Number of Events 252 252 257

Increased Glucose 18 (18.25) 17 (17.2%) 18 (18%)

Decreased WBC 9 (9.1%) 7 (7.1%) 4 (4%)

Diarrhea 14 (14.1%) 15 (15.2%) 17 (17%)

Nausea 3 (3%) 6 (6.1%) 1 (1%)

Increase ALT 4 (4%) 7 (7.1%) 8 (8%)

Increase AST 1 (1%) 7 (7.1%) 6 (6%)

Prolonged QT Interval 2 (2%) 3 (3%) 3 (3%)

Kohno S et al. AAC. 2010 Nov, 54(11): 4568-4574

Page 21: Rapivab ™ - peramivir injection Manufacturer: BioCryst Pharmaceuticals FDA Approval Date: 12/19/2014

Rapivab™ - peramivir injection

Literature Review

• Discussion: • Rapivab was well tolerated by most patients

• Patients saw improvement in influenza symptoms within 24 hours of administration

• Rapivab showed high activity against neuraminidase with a slow off rate

• Plasma concentrations of Rapivab were higher than those from standard dose of Tamiflu

Kohno S et al. AAC. 2010 Nov, 54(11): 4568-4574

Page 22: Rapivab ™ - peramivir injection Manufacturer: BioCryst Pharmaceuticals FDA Approval Date: 12/19/2014

Rapivab™ - peramivir injection

Summary

• Rapivab, peramivir, is a 600 mg, one time 15 minute IV infusion for patients who have uncomplicated influenza symptoms for less than 2 days

• Not significantly metabolized, is renally cleared and should be administered at lower doses with impaired renal function

• May decrease the efficacy of the influenza vaccine, and should not be used 48 hours prior to 2 weeks after vaccine administration

• Can cause diarrhea, hyperglycemia or neutropenia. Rarely causes serious skin reactions or neurologic complications

Page 23: Rapivab ™ - peramivir injection Manufacturer: BioCryst Pharmaceuticals FDA Approval Date: 12/19/2014

Rapivab™ - peramivir injection

References

1. http://www.rapivab.com

2. Rapivab package insert. BioCryst Pharmaceuticals. December 2014.

3. Peramivir: Drug information. Lexicomp Drug Information. Accessed through UpToDate. Accessed on January 10, 2015.

4. Kohno S et al. AAC. 2010 Nov, 54(11): 4568-4574