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HPN-100

Phase 3

Urea Cycle Disorders | Small molecule | Other |Amgen Inc.|Last Updated: Jul 11, 2024

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
RandomizedDouble-BlindACTIVE_CONTROLLEDDMCBiomarker
Total Trials5
Total Enrollment160
FDA Designations
No designations recorded
Clinical Trials (5)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT01347073Study of the Safety, Pharmacokinetics and Efficacy of HPN-100, in Pediatric Subjects With Urea Cycle Disorders (UCDs)PHASE3 COMPLETED 23 — — Jul 1, 2011Mar 1, 2013Jul 11, 20248 United States
NCT00947297Study of the Safety of HPN (Hyperion)-100 for the Long-Term Treatment of Urea Cycle Disorders (Treat UCD)PHASE3 COMPLETED 60 — — Nov 1, 2009Nov 1, 2011Jul 10, 202422 United States, Canada
NCT00992459Efficacy and Safety of HPN-100 for the Treatment of Adults With Urea Cycle DisordersPHASE3 COMPLETED 46 — — Oct 1, 2009Sep 1, 2010Jul 9, 202422 United States, Canada
NCT00947544Study of the Safety and Tolerability of HPN-100 Compared to Sodium Phenylbutyrate in Children With Urea Cycle DisordersPHASE2 COMPLETED 17 — — Mar 1, 2010Aug 1, 2011Jul 11, 20248 United States, Canada
NCT00551200Dose-Escalation Safety Study of HPN-100 to Treat Urea Cycle DisordersPHASE2 COMPLETED 14 — — Oct 1, 2007Dec 1, 2008Jul 10, 20242 United States
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Study Endpoints
Primary Endpoints
Adverse Events
2 weeks

Rate of adverse events during the Switch-Over portion of the Protocol

Rate of Adverse Events (Number of Participants Who Experienced Any AE Considered Related to Study Drug)
1 year
The Primary Endpoint Was the 24-hour Area Under the Curve for Blood Ammonia (NH324-hour AUC) on Days 14 and 28.
pre-dose, 2, 4, 8, 12, 16, 20 and 24 hours after first dose on days 14 and 28

Blood samples were collected at pre-dose, 2, 4, 8, 12, 16, 20 and 24 hours after first dose on days 14 and 28. Arm A day 14 and Arm B day 28 data were combined as a NaPBA treatment Arm. Arm B day 14 and Arm A day 28 data were combined as a HPN-100 treatment Arm.

Rate of Adverse Events During the Switchover Part of the Study Rate of Adverse Events (Number of Participants Showing Adverse Events)
1 week on each treatment for a total of 2 week.

To evaluate the safety and PK characteristics of HPN-100 compared with sodium phenylbutyrate (NaPBA) in pediatric patients with urea cycle disorders (UCDs)

Venous Ammonia Levels at the Peak and Mean TNUAC Time-normalized Area Under the Curve)
At steady state (1 week) on each medication (Buphenyl® alone, HPN-100 alone), and at steady state (1 week) after each dose escalation

Data were collected at pre-first dose and at 30 minutes and 1, 2, 4, 5, 6, 8, 10, 12, and 24 hours post first dose.

Number of Subjects Experienced Adverse Events
during the period on 100% Buphenyl (up to 4 weeks) or HPN-100 (up to 10 weeks)
Number of Subjects Experienced Serious Adverse Events
during the period subjects on 100% Buphenyl (up to 4 weeks) or HPN-100 (up to 10 weeks)
Secondary Endpoints
Blood Ammonia
2 weeks
Frequency of Ammonia Levels Greater Than the Upper Limit of Normal (ULN) on HPN-100 Compared With NaPBA
2 weeks
Hyperammonemic Crisis
1 year
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Study Design & Arms
AllocationNA
MaskingNONE
ModelSINGLE_GROUP
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
HPN-100EXPERIMENTALSwitch over from sodium phenylbutyrate to open label HPN-100 oral liquid over 10 days then open label, long term treatment for 12 months
Buphenyl (NaPBA) /HPN 100 PlaceboEXPERIMENTALSubjects in Arm A were randomly assigned to receive NaPBA + HPN 100 placebo for 2 weeks and then crossed over to receive HPN 100 + NaPBA Placebo for 2 weeks.
HPN-100/NaPBA PlaceboEXPERIMENTALSubjects in Arm B were randomly assigned to receive HPN-100 + NaPBA placebo for 2 weeks and then crossed over to receive NaPBA + HPN 100 placebo for 2 weeks.
HPN-100 and NaPBAEXPERIMENTAL1 week of NaPBA treatment followed by 1 week of HPN-100 treatment.
BUPHENYL® to HPN-100 vs. HPN-100ACTIVE_COMPARATORBuphenyl treatment for one week was followed by dose escalation to HPN-100. Dose of Buphenyl was gradually decreased while HPN-100 dose was gradually increased until subject reached dosing of 100% HPN-100. HPN-100 at 100% of the dose was given for 1 week before subject was switched back to original Buphenyl treatment.
Interventions
NameTypeDescription
HPN-100DRUGHPN-100 is a pro-drug of PAA that combines with glutamine to provide an alternative vehicle for waste nitrogen elimination. It is a liquid with minimal taste and odor. Approximately three teaspoons of HPN-100 (\~17.4 mL) delivers an equivalent amount as PBA that 40 tablets of NaPBA.
Buphenyl (NaPBA)DRUGBuphenyl (NaPBA) will be the comparator drug to HPN-100 in this study.
NaPBADRUGNaPBA tablets for oral administration and NaPBA powder for oral, nasogastric, or gastrostomy tube administration contain the active ingredient sodium phenylbutyrate. NaPBA is a prodrug and is rapidly metabolized to PAA, the metabolically active compound that conjugates with glutamine via acetylation to form PAGN, which is excreted by the kidneys.
BUPHENYL®DRUGBUPHENYL® (sodium phenylbutyrate) tablets and powder have been approved for marketing in the United States since 1996 as an adjunctive therapy in the long-term management of patients with UCDs involving deficiencies of CPS, OTC, or ASS.
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Eligibility Criteria
Age Range29 Days — 6 Years
SexALL
Healthy VolunteersNo
Study Sites8

Inclusion Criteria: * Male and female subjects 29 days to \< 6 years old. If the subject is born prematurely, calculation of the lower age limit begins at the corrected gestational age of 40 weeks. * Signed informed consent by the subject's legally acceptable representative * Suspected or confirmed...

Countries:United StatesCanada
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