Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as BMN 165 (rAvPAL-PEG), rAvPAL-PEG, Pegvaliase, PEG PAL
BMN 165 · 9 trials · 2 indications
The blood Phe measurement following 72 weeks on study is defined as the average of the Week 69 and Week 73 blood Phe measurements. Change from baseline in blood Phe will be compared between participants in the active (pegvaliase) and the control (diet-only) treatment arms. Baseline blood Phe concentration at Part 1 was defined as the average of 3 pre-treatment measurements collected between Screening/Run-in (2) and Day 1 pre-dose (1).
Treatment-emergent adverse events (TEAE) is defined as any AE that newly appeared or worsened in severity after first dose of pegvaliase (pegvaliase arm) or on or after study day 1 (diet-only arm) until 30 days after last dose of the study. Serious adverse event (SAE).
The anti-pegvaliase total antibody (TAb) method captures drug-binding antibodies comprised of different isotypes and specificities. Antibody Positivity = number of subjects testing positive at any study visit / total number of subjects at study visit. The baseline was defined as the last non-missing measurement collected prior to the first pegvaliase dose (pegvaliase arm) or prior to or on Visit 1 date (diet-only arm)
The presence of immunoglobulin G (IgG) Antibodies against phenylalanine ammonia lyase (PAL) is measured overtime. The baseline was defined as the last non-missing measurement collected prior to the first pegvaliase dose (pegvaliase arm) or prior to or on Visit 1 date (diet-only arm)
The presence of immunoglobulin M (IgM) Antibodies against PAL (phenylalanine ammonia lyase) is measured overtime. PAL IgM was positive if the titer value was greater than or equal to the median of all baseline PAL IgM titers. The baseline was defined as the last non-missing measurement collected prior to the first pegvaliase dose (pegvaliase arm) or prior to or on Visit 1 date (diet-only arm)
The presence of IgG Antibodies against polyethylene glycol (PEG) is measured overtime The baseline was defined as the last non-missing measurement collected prior to the first pegvaliase dose (pegvaliase arm) or prior to or on Visit 1 date (diet-only arm)
The presence of IgM Antibodies against PEG (polyethylene glycol) is measured overtime The baseline was defined as the last non-missing measurement collected prior to the first pegvaliase dose (pegvaliase arm) or prior to or on Visit 1 date (diet-only arm)
Neutralizing antibodies (NAbs) capable of inhibiting the enzymatic activity of pegvaliase were measured. The baseline was defined as the last non-missing measurement collected prior to the first pegvaliase dose (pegvaliase arm) or prior to or on Visit 1 date (diet-only arm)
A treatment-emergent AE was defined as any adverse event (AE) newly appearing or worsened in severity following initiation of study drug until 4 weeks after last dose of pegvaliase
Change in blood phenylalanine (Phe) concentration from Parent Study baseline (naïve/pretreatment).
Blood phe concentration in subjects previously exposed to BMN165 who were administered BMN165 20 or 40 mg/day compared with those who were administered a matching placebo.
Hypersensitivity AEs will be identified in two ways: * Broad Algorithmic anaphylactic reaction Standardized MedDRA Queries (SMQ) * Modified Hypersensitivity SMQ to include above additional preferred terms
All patients will have their plasma Phenylalanine (Phe) assessed. Please note that "Pharmacokinetics Sub-study" was not performed, and thus no results are available.
Blood Phe Concentration (Change from Baseline) and Daily Dose in PAL-003 Subjects by Disposition (PAL-003 Population)
Specifically, safety was to be assessed by examining the incidence of all treatment-emergent adverse events reported during the study period and clinically significant changes in vital signs and clinical laboratory results, including development of rAvPAL-PEG antibodies.
| Arm | Type | Description |
|---|---|---|
| Pegvaliase | EXPERIMENTAL | Treatment Arm |
| Diet Only | OTHER | Participants will be managing their PKU with diet alone. Participants in the diet-only control arm will be required to maintain and adjust dietary and medical protein food intake through Week 72, initiating pegvaliase treatment beginning Week 73 and, from Weeks 73 through 215. |
| BMN165 20mg/day | ACTIVE_COMPARATOR | BMN165 20mg/day self-administered daily |
| 20 mg/day Placebo | PLACEBO_COMPARATOR | 20 mg/day Placebo self-administered daily |
| BMN165 40mg/day | ACTIVE_COMPARATOR | BMN165 40mg/day self-administered daily |
| 40 mg/day Placebo | PLACEBO_COMPARATOR | 40 mg/day Placebo self-administered daily |
| BMN 165, 20mg/day | ACTIVE_COMPARATOR | Subjects who meet the eligibility criteria will be randomized 1:1 to titrate to one of two dose regimens: 20 mg/day or 40 mg/day. The randomization will be stratified by the last available blood Phe concentration prior to Day 1 (600 to 900 μmol/L and \> 900 μmol/L). |
| BMN 165, 40mg/day | ACTIVE_COMPARATOR | Subjects who meet the eligibility criteria will be randomized 1:1 to titrate to one of two dose regimens: 20 mg/day or 40 mg/day. The randomization will be stratified by the last available blood Phe concentration prior to Day 1 (600 to 900 μmol/L and \> 900 μmol/L). |
| Group 1 | EXPERIMENTAL | 4-8 week induction of rAvPAL-PEG at 2.5 mg, followed by titration to maintenance dose |
| rAvPAL-PEG | EXPERIMENTAL | rAvPAL-PEG in varying doses |
| rAvPAL-PEG 0.001 mg/kg | EXPERIMENTAL | Subjects will start on rAvPAL-PEG 0.001 mg/kg |
| rAvPAL-PEG 0.003 mg/kg | EXPERIMENTAL | Subjects will start on rAvPAL-PEG 0.003 mg/kg |
| rAvPAL-PEG 0.01 mg/kg | EXPERIMENTAL | Subjects will start on rAvPAL-PEG 0.01 mg/kg |
| rAvPAL-PEG 0.03 mg/kg | EXPERIMENTAL | Subjects will start on rAvPAL-PEG 0.03 mg/kg |
| rAvPAL-PEG 0.1 mg/kg | EXPERIMENTAL | Subjects will start on rAvPAL-PEG 0.1 mg/kg |
| 0.001 mg/kg | ACTIVE_COMPARATOR | One subcutaneous injection of 0.001 mg/kg of rAvPAL-PEG. |
| 0.003 mg/kg | ACTIVE_COMPARATOR | One subcutaneous injection of 0.003 mg/kg of rAvPAL-PEG. |
| 0.01 mg/kg | ACTIVE_COMPARATOR | One subcutaneous injection of 0.01 mg/kg of rAvPAL-PEG. |
| 0.03 mg/kg | ACTIVE_COMPARATOR | One subcutaneous injection of 0.03 mg/kg of rAvPAL-PEG. |
| 0.1 mg/kg | ACTIVE_COMPARATOR | One subcutaneous injection of 0.1 mg/kg of rAvPAL-PEG. |
| 0.3 mg/kg | ACTIVE_COMPARATOR | One subcutaneous injection of 0.3 mg/kg of rAvPAL-PEG. |
| 1.0 mg/kg | ACTIVE_COMPARATOR | One subcutaneous injection of 1.0 mg/kg of rAvPAL-PEG. |
| Name | Type | Description |
|---|---|---|
| Pegvaliase | DRUG | Pegvaliase 2.5mg/10mg/20mg/40mg/60mg self-administered from 1 time up to 7 times a week |
| Diet Only | OTHER | Diet Control |
| BMN165 20mg/day | DRUG | BMN165 20mg/day self-administered daily |
| BMN165 40mg/day | DRUG | BMN165 40mg/day self-administered daily |
| Placebo | DRUG | Non-drug placebo, self-administered daily |
| BMN 165 | DRUG | After informed consent, eligible subjects will be randomized (1:1) to titrate up to one of two dose regimens: 20 mg/day or 40 mg/day. All subjects will initiate IP at a fixed-dose of 2.5 mg/week for 4 weeks (Induction). After the Induction Period, subjects will enter the Titration Period (Weeks 5 up to 34) where they will increase their weekly BMN 165 dose to a daily dose regimen of 20 mg/day or 40 mg/day. The Titration Period will be individualized to each subject based on a minimum of 6 weeks (the amount of time it takes to reach a dose regimen of 20 mg/day with no dose interruptions) and up to 30 weeks (accounts for dose reduction or interruption due to AEs). Subjects will stop titration once they have achieved either the 20 mg/day or 40 mg/day dose regimen. The majority of subjects will maintain the 20 or 40 mg/day dose regimen for at least an additional 2 weeks until a minimum of approximately 26 weeks or a maximum of 36 weeks in the study. |
| BMN 165 (rAvPAL-PEG) | BIOLOGICAL | Subcutaneous injection of rAvPAL-PEG administered from 1 time up to 5 times per week between 2.5mg up to a maximum of 375mg for 24 weeks. |
| rAvPAL-PEG | DRUG | 0.06 mg/kg/day, 0.1 mg/kg/day, 0.2 mg/kg/day, 0.4 mg/kg/day, 0.6 mg/kg/day, 0.8 mg/kg/day |
| rAvPAL-PEG 0.001 mg/kg | DRUG | In Part 1, the planned starting dose levels is 0.001 mg/kg |
| rAvPAL-PEG 0.003 mg/kg | DRUG | In Part 1, the planned starting dose levels is 0.003 mg/kg |
| rAvPAL-PEG 0.01 mg/kg | DRUG | In Part 1, the planned starting dose levels is 0.01 mg/kg |
| rAvPAL-PEG 0.03 mg/kg | DRUG | In Part 1, the planned starting dose levels is 0.03 mg/kg |
| rAvPAL-PEG 0.1 mg/kg | DRUG | In Part 1, the planned starting dose levels is 0.1 mg/kg |
Inclusion Criteria * Is 12 to 17 years old (US), inclusive, or 12 to 15 years (EU), inclusive, at the start of the Screening/Run-in Period (Day -28). * Diagnosis of PKU and failure to maintain recommended blood Phe levels on existing management (sapropterin dihydrochloride and Phe-restricted diet) ...
Top 5 of 7 competitors
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| BioMarin Pharmaceutical Inc. | BMRN | 5 | PHASE3 | Pegvaliase, BMN 307 |
| PTC Therapeutics, Inc. | PTCT | 1 | PHASE3 | Sepiapterin |
| Maze Therapeutics, Inc. | MAZE | 1 | PHASE2 | MZE782 |
| Sanofi SA Sponsored ADR | SNY | 1 | PHASE1 | SAR444836 |
| Agios Pharmaceuticals, Inc. | AGIO | 1 | PHASE1 | AG-181 |
BMN 165 is an investigational therapy developed for the treatment of phenylketonuria, or PKU, a metabolic disorder. It was studied in adults with PKU, including patients who had not previously received the therapy. All three of its listed clinical trials enrolled adults with PKU in the United States.
BMN 165 is developed by BioMarin Pharmaceutical Inc., which trades on Nasdaq under the ticker BMRN. BioMarin sponsored the Phase 2 and Phase 3 clinical trials of BMN 165 in phenylketonuria, including the active-controlled Phase 3 study and the open-label Phase 3 study.
BMN 165 reached Phase 3 clinical development for phenylketonuria. Three trials are listed for the program: two Phase 3 studies and one Phase 2 study, and all three are completed. No trials are currently active, and the program remains investigational rather than approved.
BMN 165 has been studied in three completed trials: NCT01889862, a Phase 3 active-controlled study of self-administered injections in adults with PKU; NCT01819727, an open-label Phase 3 study in adults with PKU not previously treated with BMN 165; and NCT01560286, a Phase 2 study of subcutaneously administered rAvPAL-PEG.
Yes. BMN 165 is also known as rAvPAL-PEG, and it has appeared in trial listings under names such as BMN 165 (rAvPAL-PEG), BMN165 20mg/day, and BMN165/day. These names refer to the same BioMarin phenylketonuria program, including the Phase 2 study of subcutaneously administered rAvPAL-PEG.
The BMN 165 clinical program enrolled about 500 patients across three completed trials. The Phase 3 study NCT01889862 enrolled 215 adults, the open-label Phase 3 study NCT01819727 enrolled 261 adults, and the Phase 2 study NCT01560286 enrolled 24 patients. The Phase 3 trials were randomized, double-blind, and active-controlled.