Drugs

Drug Trial Snapshot: PALYNZIQ

 

HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the clinical trials that supported the FDA approval of this drug, and whether there were differences among sex, race and age groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.

LIMITATIONS OF THIS SNAPSHOT:
Do not rely on Snapshots to make decisions regarding medical care. Always speak to your health provider about the risks and benefits of a drug. Refer to the PALYNZIQ Package Insert for complete information.

PALYNZIQ (pegvaliase-pqpz)
pal-lin-zeek
BioMarin Pharmaceutical, Inc.
Approval date:May 24, 2018


DRUG TRIALS SNAPSHOT SUMMARY:

What is the drug for?

PALYNZIQ is a drug used to lower blood levels of phenylalanine in adults with phenylketonuria (PKU), who have high phenylalanine blood levels on current treatment.

Phenylketonuria is a rare inherited disorder that, if left untreated, causes brain damage and disability because of buildup of phenylalanine in the body.

How is this drug used?

PALYNZIQ is injected under the skin (subcutaneous). The initial dose is injected once weekly for four weeks. Afterwards, the dose is adjusted following a special schedule.

What are the benefits of this drug?

Patients treated with PALYNZIQ had lower levels of blood phenylalanine concentrations and were able to maintain low concentrations in comparison to patients who received placebo treatment.

What are the benefits of this drug (results of trials used to assess efficacy)?

The table below summarizes efficacy results for Trial 2 based on the Intent-to-Treat (ITT) population. Demographics of that population is presented in Table 7 under MORE INFO. 

Table 2. Primary Endpoint: LS Mean Change in Blood Phenylalanine Concentration from Randomized Withdrawal Baseline to Week 8 in Adult Patients with PKU- Efficacy Assessment in Trial 2

Randomized Study Arm

Blood Phenylalanine Concentration (micromol/L)
Mean (SD)

LS Mean Change from
Trial 2 Randomized Withdrawal Baseline to
Week 8

(95% CI)

Treatment
Difference
in LS Mean Change
(95% CI)
P-value*

Pre-treatment
Baseline

Trial 2
Randomized Withdrawal Baseline

Trial 2
Randomized Withdrawal Week 8

PALYNZIQ 20 mg once daily

1450.2 (310.5)
n = 29

596.8 (582.8)
n = 29

553.0 (582.4)
n = 26†

-23.3
(-156.2, 109.7)

-973.0
(‑1204.2, ‑741.9)
p < 0.0001

Placebo 20 mg once daily

1459.1 (354.7)
n = 14

563.9 (504.6) n = 14

1509.0 (372.6)
n = 13†

949.8
(760.4, 1139.1)

PALYNZIQ 40 mg once daily

1185.8 (344.0)
n = 29

410.9 (440.0)
n = 29

566.3 (567.5)
n = 23†

76.3
(-60.2, 212.8)

-588.5
(-830.1, -346.9)
p < 0.0001

Placebo 40 mg once daily

1108.9 (266.8)
n = 14

508.2 (363.7) n = 14

1164.4 (343.3) n = 10†

664.8
(465.5, 864.1)

* Based on the mixed model repeated measures (MMRM) method, with treatment arm, visit, and treatment arm-by-visit interaction as factors adjusting for baseline blood phenylalanine concentration.
† Patients who did not complete phenylalanine assessment within the window for Week 8 (Day 43 to 56) were excluded.
PALYNZIQ Prescribing Information

Were there any differences in how well the drug worked in clinical trials among sex, race and age?

  • Sex: PALYNZIQ worked similarly in males and females.
  • Race: The majority of patients were White. The number of patients in other races was limited; therefore, differences in side effects among races could not be determined.
  • Age: The majority of patients were adults 18-65 years of age; therefore, differences in response among different age groups could not be determined.

    Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?

    Figures 4 and 5 below summarize the results for the primary efficacy endpoint, change in blood phenylalanine concentration from baseline to Week 8 of the randomized withdrawal period, by sex and age.

    Figure 4. Mean Change from Part 2 Baseline at Week 8 in the ITT Population (20 mg/day versus Placebo)

    Figures  summarize efficacy results by sex and age subgroup.

    FDA Review

    Figure 5. Mean Change from Part 2 Baseline at Week 8 in the ITT Population (40 mg/day versus Placebo)

    Figures  summarize efficacy results by sex and age subgroup.

    FDA Review

    What are the possible side effects?

    PALYNZIQ may cause serious side effects including life threatening allergic reaction called anaphylaxis.

    The most common side effects of PALYNZIQ are injection site reactions, joint pain, hypersensitivity reactions, headache, and various skin reactions.

    What are the possible side effects (results of trials used to assess safety)?

    The table below summarizes adverse reactions, in patients with phenylketonuria, who received at least one dose of PALYNZIQ.

    Table 3. Adverse Reactions* Reported in at Least 15% of PKU Patients Treated with PALYNZIQ in an Induction/Titration/Maintenance Regimen in Clinical Trials- Incidence and Exposure-Adjusted Rates

    Treatment Phase

    Induction/Titration Phase (N = 285)

    Maintenance Phase (N = 223)

    Treatment Duration

    135 person-years
    Mean: 178 days
    Median: 116 days
    Range: 1 to 1607 days

    444 person-years
    Mean: 739 days
    Median: 697 days
    Range: 5 to 1561 days

    Adverse Reaction

    N (%)†

    Episodes (Rate)†

    N (%)†

    Episodes (Rate)†

    Injection site reactions‡

    252 (88%)

    2964 (21.9)

    161 (72%)

    1754 (4)

    Arthralgia§

    210 (74%)

    1035 (7.6)

    137 (61%)

    661 (1.5)

    Hypersensitivity reactions¶

    152 (53%)

    633 (4.7)

    135 (61%)

    663 (1.5)

    Headache#

    100 (35%)

    211 (1.6)

    111 (50%)

    778 (1.8)

    Generalized skin reaction lasting at least 14 daysÞ

    61 (21%)

    95 (0.7)

    82 (37%)

    133 (0.3)

    Pruritus

    58 (20%)

    100 (0.7)

    53 (24%)

    402 (0.9)

    Nausea

    51 (18%)

    66 (0.5)

    57 (26%)

    106 (0.2)

    Dizziness

    46 (16%)

    64 (0.5)

    38 (17%)

    72 (0.2)

    Abdominal painß

    39 (14%)

    53 (0.4)

    55 (25%)

    128 (0.3)

    Oropharyngeal pain

    38 (13%)

    43 (0.3)

    51 (23%)

    70 (0.2)

    Fatigue

    37 (13%)

    81 (0.6)

    48 (22%)

    86 (0.2)

    Vomiting

    36 (13%)

    53 (0.4)

    58 (26%)

    100 (0.2)

    Cough

    27 (9%)

    33 (0.2)

    50 (22%)

    65 (0.2)

    Diarrhea

    25 (9%)

    31 (0.2)

    50 (22%)

    91 (0.2)

    Anxiety

    14 (5%)

    23 (0.2)

    41 (18%)

    79 (0.2)

    Alopecia

    13 (5%)

    14 (0.1)

    39 (17%)

    50 (0.1)

    Nasal congestion

    12 (4%)

    15 (0.1)

    41 (18%)

    50 (0.1)

    * ≥ 15% incidence in either treatment phase

    † N (%) = Number of patients with at least 1 Adverse Reaction (%); Rate = Exposure-Adjusted Rate of Adverse Reactions (Adverse Reactions/Person Years)

    ‡ Includes Injection site: reaction, erythema, pruritus, pain, bruising, rash, swelling, urticaria, induration, hemorrhage, edema, mass, inflammation, nodule, discoloration, warmth, hematoma, irritation, vesicles, hypersensitivity, papule, discomfort, scar, paresthesia, hypertrophy, extravasation, and dryness

    § Includes arthralgia, pain in extremity, back pain, musculoskeletal pain, neck pain

    ¶ Includes rash, urticaria, anaphylaxis, rash generalized, hypersensitivity, rash erythematous, rash maculo-papular, rash pruritic, serum sickness, swelling face, dermatitis contact, swollen tongue, lip swelling, rash macular, pharyngeal edema, injection site hypersensitivity, eczema, drug eruption, dermatitis allergic, dermatitis, tongue edema, palatal edema, edema mouth, multiple allergies, lip edema, eye edema, exfoliative rash, drug hypersensitivity, dermatitis atopic, dermatitis acneiform, pruritus allergic, mouth swelling, implant site rash, gingival swelling, face edema, eyelid edema, eye swelling, dermatitis psoriasiform, dermatitis infected, conjunctivitis allergic, bronchospasm, angioedema, allergic sinusitis, allergic cough

    # Includes headache, migraine, sinus headache

    Þ Includes pruritus, rash, urticaria, dry skin, rash erythematous, erythema, cellulitis, rash macular, pruritus generalized, petechiae, dermatitis allergic, skin infection, skin induration, rash maculo-papular, rash generalized, pharyngeal edema, macule, granulomatous dermatitis, exfoliative rash, drug eruption, dermatitis atopic, dermatitis, xanthogranuloma, skin plaque, skin mass, skin lesion, skin hypopigmentation, skin hypertrophy, skin hyperpigmentation, skin exfoliation, septal panniculitis, scleroderma, scar, rash pruritic, rash papular, psoriatic arthropathy, pruritus allergic, papule, necrobiosis lipoidica diabeticorum, furuncle, eczema, ecchymosis, dermatitis psoriasiform, dermatitis infected, blister

    ß Includes abdominal pain, abdominal pain upper, abdominal discomfort

    PALYNZIQ Prescribing Information

     

    Were there any differences in side effects among sex, race and age?

    • Sex: The occurrence of certain hypersensitivy side effects was higher in females than males.
    • Race: The majority of patients were White. The number of patients in other races was limited; therefore, differences in side effects among races could not be determined.
    • Age: The majority of patients were adults 18-65 years of age; therefore, differences in side effects among different age groups could not be determined.

     

    Were there any differences in side effects of the clinical trials among sex, race, and age groups?

    The table below summarizes three most frequent adverse reactions by sex using number of events (exposure-adjusted event rate). Race and age subgroups are not presented because the trial population consisted of predominantly White patients 18-65 years of age.

    Table 4. Adverse Reactions by Sex (safety population)

     

    Male (N=142)
    Events (Event Rate)

    Female (N=143)
    Events (Event Rate)

    Total treatment exposure (person-years)

    248

    225.4

    Injection site  reactions

    115 (0.46)

    224 (0.99)

    Arthralgia

    385 (1.55)

    799 (3.54)

    Hypersensitivity

    1237 (4.99)

    2281 (10.12)

    FDA Review

    WHO WAS IN THE CLINICAL TRIAL?

    Who participated in the clinical trials?

    The FDA approved PALYNZIQ based on evidence from 2 clinical trials, Trial 1 (NCT01819727) and Trial 2 (NCT01889862) which included 285 adult patients with phenylketonuria. The trials were conducted at 60 sites in the United States.

    Figure 1 summarizes how many males and females were enrolled in the clinical trials used to evaluate safety.

    Figure 1. Baseline Demographics by Sex (safety population)

    Pie chart summarizing how many men and women were in the clinical trials. In total, 142 men (50%) and 143 women (50%) participated in the clinical trials.

    Figure 2. Baseline Demographics by Race (safety population)

    Pie chart summarizing the percentage of patients by race in the clinical trials. In total, 278 White (98%), 3 Black or African American (1%), 4 other race patients (1%) where in the clinical trials.

    FDA Review

    Table 1. Baseline Demographics by Race (safety population)

    Race

    Number of Patients

    Percentage

    White

    278

    98%

    Black or African American

    3

    1%

    American Indian or Alaska Native

    1

    less than 1%

    Other

    2

    less than 1%

    Missing

    1

    less than 1%

    FDA Review

    Figure 3 summarizes the percentage of patients by age based on the safety population.

    Figure 3. Baseline Demographics by Age

    Pie chart summarizing how many individuals of certain age groups were in the clinical trials. In total, 12 patients were 16-18 years old (4%) and 273 patients were 18-65 years old (96%).

    FDA Review

    Who participated in the Trials

    The table blow summarizes demographics of all patients in the safety population.

    Table 5. Demographic Characteristics of Safety Population

    Demographic Parameters

    All Patients
    N=285
    n (%)

    Sex

    Male

    142 (49.8%)

    Female

    143 (50.2%)

    Race

    White

    278 (97.5%)

    Black or African American

    3 (1.1%)

    American Indian or Native Alaskan

    1 (<1%)

    Other

    2 (<1%)

    Missing

    1 (<1 %)

    Age

    16  to < 18 years of age

    12 (4.2%)

    18  to  < 65 years of age

    273 (95.8%)

    Ethnicity

    Hispanic

    7 (2.5%)

    Not Hispanic

    277 (97.2%)

    Missing

    1 (<1%)

    Region

    United States

    285 (100.0%)

    FDA Review

    The table below summarizes demographics of intent to treat population from the Trial 2 used to assess the efficacy.

    Table 6. Demographic Characterisitics of the Intent-to-Treat Population (ITT)

    Naive Demographic or Baseline Characteristic

     

    PALYNZIQ
    20 mg/day
    (N=29)

    PALYNZIQ
    40 mg/day
    (N=29)

    Placebo
    20 mg/day
    (n = 14)

    Placebo
    40 mg/day
    (n = 14)

    Sex

    Female

    14 (48.3%)

    17 (58.6%)

    6 (42.9%)

    6 (42.9%)

    Male

    15 (51.7%)

    12 (41.4%)

    8 (57.1%)

    8 (57.1%)

    Race

    White

    29 (100.0%)

    29 (100.0%)

    13 (92.9%)

    14 (100.0%)

    Black/African American

    0

    0

    1 (7.1%)

    0

    Age, years

    Mean (SD)

    30.72 (9.1)

    28.59 (7.6)

    30.50 (10.9)

    30.00 (10.2)

    Median

    29.0

    29.0

    27.5

    25.5

    Min, Max

    19, 50

    16, 40

    19, 51

    18, 50

    16 to < 18 years old

    0

    3 (10.3%)

    0

    0

    18 to < 65 years old

    29 (100.0%)

    26 (89.7%)

    14 (100.0%)

    14 (100.0%)

    Region

    United States

    29 (100%)

    29 (100%)

    14 (100%)

    14 (100%

    FDA Review

    How were the trials designed?

    The benefit and side effects of PALYNZQ were evaluated in two clinical trials of adult patients with phenylketonuria (PKU). Each trial had a different design and treatment duration.

    Trial 1: Trial evaluated patients with high phenylalanine blood concentrations who had never been treated before with PALYNZIQ. All patients received PALYNZIQ for up to 36 weeks, starting with low doses given once weekly up to the maximum dose given once daily. The trial data were used to assess the side effects of PALYNZIQ.

    Trial 2: Patients, who were previously treated with PALYNZIQ, received up to an additional 13 weeks of PALYNZIQ. After that, if patients achieved at least a 20% decrease in blood phenylalanine concentration from their pre-treatment levels, they were randomly assigned to continue PALYNZIQ or to switch to placebo for 8 weeks. The benefit of PALYNZIQ was assessed by measuring the level of phenylalanine in the blood at the end of 8 weeks.

    How were the trials designed?

    The safety and efficacy of PALINZIQ was evaluated in two clinical trials of adult patients with phenylketonuria (PKU).

    Trial 1 (NCT01819727) evaluated PALYNZIQ, in adult patients with PKU , who had inadequate phenylalanine blood concentrations on existing management. This trial was an open-label, randomized, multi-center clinical trial. Patients were treated with PALYNZQ with an induction/titration/maintenance regimen, gradually increasing from weekly low doses to daily higher doses. Patients were randomized to receive PALYNZIQ target maintenance doses at 20 mg or 40 mg once daily for up to 36 weeks. The primary objective of this trial was to assess PALYNZIQ safety.

    Trial 2 (NCT01889862) evaluated PALYNZIQ in adult patients with PKU previously-treated with PALYNZIQ. Enrolled patients included patients from Trial 1 and other PAYNZIQ trials. Patients received PALYNZIQ treatment up to an additional 13 weeks. If patients achieved > 20% reduction in blood phenylalanine concentration from their pre-treatment baseline concentration (in previous trials), they were enrolled into the efficacy assessment period (randomized withdrawal period). In the randomized withdrawal period, patients were randomized to continue PALYNZIQ or receive placebo for 8 weeks. The efficacy endpoint was the change in blood phenylalanine concentration from baseline to Week 8 of the randomized withdrawal period.

    GLOSSARY

    CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.


    COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.


    EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.


    PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.


    SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.

    PRESCRIBING INFORMATION

    Back to Drug Trials Snapshots

 

 

Page Last Updated: 06/21/2018
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