About HYRIMOZ®

Indications have been granted on the basis of similarity between HYRIMOZ® and the reference biologic drug, Humira®.1

HYRIMOZ® (adalimumab) is indicated for: 

Reducing the signs and symptoms, inducing major clinical response and clinical remission, inhibiting the progression of structural damage and improving physical function in adult patients with moderately to severely active Rheumatoid Arthritis (RA). HYRIMOZ® can be used alone or in combination with methotrexate (MTX) or other disease-modifying anti-rheumatic drugs (DMARDs). HYRIMOZ® should be given in combination with MTX when used as first-line treatment in recently diagnosed patients who have not been previously treated with MTX. HYRIMOZ® can be given as monotherapy in case of intolerance to methotrexate or when treatment with methotrexate is contraindicated.

In combination with methotrexate, reducing signs and symptoms of moderately to severely active Polyarticular Juvenile Idiopathic Arthritis (JIA) in patients, 2 years of age and older who have had an inadequate response to one or more DMARDs. HYRIMOZ® can be used as monotherapy in case of intolerance to methotrexate or when continued treatment with MTX is not appropriate. Adalimumab has not been studied in pediatric patients with JIA aged less than 2 years.

Reducing the signs and symptoms of active arthritis and inhibiting the progression of structural damage and improving the physical function in adult Psoriatic Arthritis (PsA) patients. HYRIMOZ® can be used in combination with MTX in patients who do not respond adequately to methotrexate alone.

Reducing signs and symptoms in patients with active Ankylosing Spondylitis (AS) who have had an inadequate response to conventional therapy.

Reducing signs and symptoms and inducing and maintaining clinical remission in adult patients with moderately to severely active Crohn’s disease (CD) who have had an inadequate response to conventional therapy, including corticosteroids and/or immunosuppressants. HYRIMOZ® is indicated for reducing signs and symptoms and inducing clinical remission in these patients if they have also lost response to or are intolerant to infliximab.

Treatment of adult patients with moderately to severely active Ulcerative Colitis (UC) who have had an inadequate response to conventional therapy including corticosteroids and/or azathioprine or 6-mercaptopurine (6-MP) or who are intolerant to such therapies. The efficacy of adalimumab in patients who have lost response to or were intolerant to TNF blockers has not been established.

Treatment of active moderate to severe Hidradenitis Suppurativa (HS) in adult patients, who have not responded to conventional therapy (including systemic antibiotics).

Treatment of adult patients with chronic moderate to severe Plaque Psoriasis (PsO) who are candidates for systemic therapy. For patients with chronic moderate PsO, HYRIMOZ® should be used after phototherapy has been shown to be ineffective or inappropriate.

Treatment of non-infectious Uveitis (NIU) (intermediate, posterior and panuveitis) in adult patients with inadequate response to corticosteroids or as corticosteroid sparing treatment in corticosteroid-dependent patients.

 


 

Consider HYRIMOZ®

OFFERING TREATMENT OPTIONS FOR YOU AND YOUR PATIENTS

Single-dose pre-filled HYRIMOZ®SensoReady®Pen, with a hidden 29-gauge, ½-inch, 5-bevel needle4

Single-dose pre-filled glass syringe with a needle guard and add-on finger flange, and a 29-gauge, ½-inch, 5-bevel needle, available in two dosage strengths4

WITH DEMONSTRATED EFFICACY AND SAFETY PROFILE

Efficacy profile from ADACCESS (PsO):*

The ADACCESS switch study met its primary objective – a comparable PASI75 response rate between HYRIMOZ® and the reference adalimumab (EU and US formulations of Humira®) at week 16.1,2

The 95% CI of the adjusted treatment difference for both EU-Humira® vs HYRIMOZ® (-6.79, 11.10) and US-Humira® vs HYRIMOZ® (-4.39, 14.61) remained within the predefined equivalence margin of [-18%, 18%].

 

Safety profile:

The types, frequency and severity of adverse events were comparable between HYRIMOZ® and the reference adalimumab (Humira®).1

The most common adverse reaction was injection site reactions (13% of adalimumab-treated patients developed injection site reactions)

Most injection site reactions were described as mild and generally did not necessitate drug discontinuation.

 

Adalimumab safety profile in PsO:

TEAEs possibly or probably related to adalimumab that were reported in ≥1% of PsO patients in two controlled studies included: injection-site reaction (3.0%), headache (2.0%), injection-site irritation (1.7%), injection-site pain (1.5%), upper respiratory infection (1.2%), arthralgia (1.0%), fatigue (1.0%), and nausea (1.0%).

 

* A phase III, randomized, double-blind, multicentre, comparator-controlled study with treatment switches to rule out any clinically meaningful difference between HYRIMOZ® (N=231) and the reference adalimumab (EU-Humira®, N=44; US-Humira®, N=190) in 465 patients with moderate to severe chronic plaque-type psoriasis (PsO). The primary efficacy endpoint was the PASI75 (defined as a 75% reduction of the PASI) response rate measured at week 16.

 

SANDOZ: A DIVISION OF NOVARTIS – A DEDICATED PARTNER IN IMMUNOLOGY CARE IN CANADA

Offering treatment options across 9 indications in Immunology, including RA, JIA, PsA, AS, CD, UC, HS, PsO, NIU

Sandoz and Novartis share capabilities, manufacturing facilities and biologics manufacturing expertise

 

PsO: plaque psoriasis; PASI: psoriasis area and severity index; TEAE: treatment-emergent adverse event; RA: rheumatoid arthritis; JIA: polyarticular juvenile idiopathic arthritis; PsA: psoriatic arthritis; AS: ankylosing spondylitis; CD: Crohn’s disease; UC: ulcerative colitis; HS: Hidradenitis Suppurativa; NIU: non-infectious uveitis.

Select HYRIMOZ® bioequivalence criteria

HYRIMOZ® AND REFERENCE ADALIMUMAB (EU-HUMIRA®) PHARMACOKINETIC FACTORS*1

 

Parameter HYRIMOZ® Reference

adalimumab†‡
% Ratio of

Geometric Means

(90% Confidence

Interval)
AUCT

(mcg•h/mL)
2261

2489 (42.0)
2163

2326 (37.5)
104.6

(94.7 - 115.4)
AUCI

(mcg•h/mL)
2728

2952 (41.5)
2557

2719 (35.1)
106.7

(97.6 - 116.6)
CMAX

(mcg/mL)
3.67

3.84 (29.0)
3.54

3.70 (29.9)
103.8

(96.7 - 111.5)
* n=104 for AUCT, and CMAX; n=99 for AUCI
† Reference adalimumab: EU- Humira®
‡ n=103 for AUCT, and CMAX; n=101 for AUCI
§ Least square mean, estimated using analysis of variance with treatment as fixed effect.
* Based on a 1x 40mg adalimumab injection in healthy patients from measured data.

 


DEMONSTRATED EFFICACY IN PsO


 

HYRIMOZ®: THE ADACCESS PIVOTAL TRIAL1

A phase III, randomized, double-blind, multicentre, comparator-controlled study with treatment switches to rule out any clinically meaningful difference between HYRIMOZ® and the reference adalimumab (Humira®)* in patients with moderate to severe chronic plaque-type psoriasis (PsO).

  • The primary efficacy endpoint was the PASI75 (defined as a 75% reduction of the PASI) response rate measured at week 16.

 

The 95% CI of the adjusted treatment difference for both EU-Humira® vs HYRIMOZ® and US- Humira® vs HYRIMOZ® remained within the predefined equivalence margin of [-18%, 18%].

 

CI: confidence intervals; EI: equivalence interval; n: number of patients per treatment group achieving PASI75 response; N: number of patients per treatment group; PASI: psoriasis area and severity index; SE: standard error.

* The patient population consisted of adult male and female patients with active, but clinically stable chronic plaque-type skin psoriasis involving a BSA of at least 10%, a minimal PASI of 12 (indicating moderate-to-severe psoriasis), and an IGA of at least moderate severity (score ≥3). Eligible patients had to have previously received at least one phototherapy or systemic therapy for psoriasis or were candidates to receive such therapy in the opinion of the investigator. Randomization at baseline was stratified by body weight (<90kg and ≥90kg), by prior systemic psoriasis therapy and by region (EU and US).

† In TP1, eligible patients were randomized 1:1 to receive an initial dose of 80 mg subcutaneous HYRIMOZ® or the reference adalimumab (EU or US-Humira®), followed by 40 mg every other week, starting 1 week after the initial dose until week 15. Randomization was stratified by prior systemic therapy, region and body weight, and was performed centrally.

‡ Adjusted response rates were estimated using a logistic regression model including treatment, body weight strata, region and prior systemic therapy. The 95% CI for the rate difference was derived based on the normal approximation and standard error computed using the delta method (method details and code were adopted from Ge et al 2011). Patients with missing PASI scores at week 16 regardless of reason (e.g. missing visit, early discontinuation) are considered non-responders for the analysis.

 

Indications have been granted on the basis of similarity between HYRIMOZ® and the reference biologic drug Humira®.1

RHEUMATOLOGY1

HYRIMOZ® (adalimumab) is indicated for:

Reducing the signs and symptoms, inducing major clinical response and clinical remission, inhibiting the progression of structural damage and improving physical function in adult patients with moderately to severely active Rheumatoid Arthritis (RA). HYRIMOZ® can be used alone or in combination with methotrexate (MTX) or other disease-modifying anti-rheumatic drugs (DMARDs).

In combination with methotrexate, reducing signs and symptoms of moderately to severely active Polyarticular Juvenile Idiopathic Arthritis (JIA) in patients, 2 years of age and older who have had an inadequate response to one or more DMARDs. HYRIMOZ® can be used as monotherapy in case of intolerance to methotrexate or when continued treatment with MTX is not appropriate. Adalimumab has not been studied in pediatric patients with JIA aged less than 2 years.

Reducing the signs and symptoms of active arthritis and inhibiting the progression of structural damage and improving the physical function in adult Psoriatic Arthritis (PsA) patients. HYRIMOZ® can be used in combination with MTX in patients who do not respond adequately to methotrexate alone.

Reducing signs and symptoms in patients with active Ankylosing Spondylitis (AS) who have had an inadequate response to conventional therapy.


 

GASTROENTEROLOGY1

HYRIMOZ® (adalimumab) is indicated for:

Reducing signs and symptoms and inducing and maintaining clinical remission in adult patients with moderately to severely active Crohn’s disease (CD) who have had an inadequate response to conventional therapy, including corticosteroids and/or immunosuppressants. HYRIMOZ® is indicated for reducing signs and symptoms and inducing clinical remission in these patients if they have also lost response to or are intolerant to infliximab.

Treatment of adult patients with moderately to severely active Ulcerative Colitis (UC) who have had an inadequate response to conventional therapy including corticosteroids and/or azathioprine or 6-mercaptopurine (6-MP) or who are intolerant to such therapies. The efficacy of adalimumab in patients who have lost response to or were intolerant to TNF blockers has not been established.


 

DERMATOLOGY1

HYRIMOZ® (adalimumab) is indicated for:

Treatment of active moderate to severe Hidradenitis Suppurativa (HS) in adult patients, who have not responded to conventional therapy (including systemic antibiotics).

Treatment of adult patients with chronic moderate to severe Plaque Psoriasis (PsO) who are candidates for systemic therapy. For patients with chronic moderate PsO, HYRIMOZ® should be used after phototherapy has been shown to be ineffective or inappropriate.


 

OPHTHALMOLOLOGY1

HYRIMOZ® (adalimumab) is indicated for:

Treatment of non-infectious Uveitis (NIU) (intermediate, posterior and panuveitis) in adult patients with inadequate response to corticosteroids or as corticosteroid sparing treatment in corticosteroid-dependent patients.

 

Storage, stability, and disposal

HYRIMOZ®: COMMITTED TO OFFERING FORMAT OPTIONS TO YOU AND YOUR PATIENTS1,3

HYRIMOZ® SINGLE-USE PREFILLED SENSOREADY® PEN

40 mg/0.8 mL*

  • Hidden 29-gauge, 1/2-inch, 5-bevel needle
  • Triangular shape to facilitate grip and not roll
  • Automatic activation with audible and visual cues – 2 loud clicks and a green indicator

HYRIMOZ® SINGLE-USE PREFILLED GLASS SYRINGE WITH NEEDLE GUARD

40 mg/0.8 mL* and 20 mg/0.4 mL*

  • 29-gauge, 1/2-inch, 5-bevel needle
  • Two dosage strengths
  • Needle guard automatically covers needle after injection
  • Add-on finger flange
* Patients may self-inject only if their physician determines that it is appropriate and with medical follow-up, as necessary, after proper training in measurement of the correct dose and injection technique.

 

Physiolis technology: Offering devices with thin and sharp needles.4

 

HYRIMOZ®: COMMITTED TO PROVIDING STORAGE OPTIONS FOR YOUR PATIENTS1

Keep refrigerated at 36°F to 46°F (2°C to 8°C)
  • DO NOT FREEZE.
  • Do not use if frozen even if it has been thawed.
May be stored at room temperature for a period of up to 21 days.
  • Up to a maximum of 77°F (25°C).
  • Discard if not used within the 21-day period.
  • Record the date when HYRIMOZ® is first removed from the refrigerator in the spaces provided on the carton.
Whether storing HYRIMOZ® in the fridge or at room temperature, protect from light.
Do not store HYRIMOZ® in extreme heat or cold.
Do not use beyond the expiration date on the container.

 

HYRIMOZ® can be stored at room temperature for up to 21 days.

 


HYRIMOZ® DOSING FOR INDICATIONS IN RHEUMATOLOGY1

Rheumatoid Arthritis

Psoriatic Arthritis

  • Recommended dose: 40 mg SC administered EOW.*

Ankylosing Spondylitis

  • The recommended dose for patients with polyarticular JIA from 2 years of age is based on body weight.†‡
    • 10 kg to < 30 kg*: 20 mg SC EOW
    • ≥ 30 kg: 40 mg SC EOW HYRIMOZ® can be used in combination with MTX or as monotherapy in case of intolerance to MTX or when continued treatment with MTX is not appropriate

Polyarticular Juvenile Idiopathic Arthritis

  • Recommended dose: 40 mg SC administered EOW.*
  • Glucocorticoids, salicylates, nonsteroidal anti-inflammatory drugs, analgesics or disease modifying anti-rheumatic drugs can be continued during treatment with HYRIMOZ®.
SC: subcutaneous injection ; EOW: every other week ; MTX: Methotrexate,

* Available data suggest that the clinical response is usually achieved within 12 weeks of treatment. Continued therapy should be carefully reconsidered in a patient not responding within this time period.

† Safety and effectiveness in pediatric patients with JIA less than 2 years of age or in patients with a weight below 10 kg have not been established. Available data suggest that clinical response is usually achieved within 12 weeks of treatment. Efficacy and safety in patients who do not respond by Week 16 have not been established.

‡ A dose of 10 mg every other week can be considered for patients weighing 10 to <15 kg. A different adalimumab product should be considered as there are no available presentations of HYRIMOZ® capable of delivering 10 mg.
For full dosing and administration information, please see the Product Monograph.

 


 

HYRIMOZ® DOSING FOR INDICATIONS IN GASTROENTEROLOGY1

Crohn’s Disease

Recommended induction dose:

  • 160 mg SC at week 0
    • Can be given in one day (four 40 mg injections) or split over two consecutive days (two 40 mg injections each day)
  • 80 mg SC at week 2
    • Given as two 40 mg injections in one day

During treatment with HYRIMOZ®:*

  • Other concomitant therapies (e.g., corticosteroids and/or immunomodulatory agents) should be optimized.
  • For patients who experience a disease flare, dose escalation may be considered.
 

Recommended maintenance dose:*

  • 40 mg EOW beginning at week 4

Ulcerative Colitis

Recommended induction dose:

  • 160 mg SC at week 0
    • Can be given in one day (four 40 mg injections) or split over two consecutive days (two 40 mg injections each day)
  • 80 mg SC at week 2
    • Given as two 40 mg injections in one day

During treatment with HYRIMOZ®:*

  • Aminosalicylates and/or corticosteroids may be continued
  • Azathioprine and 6-mercaptopurine (6-MP) may be continued if necessary
 

Recommended maintenance dose:*

  • 40 mg every other week beginning at week 4
  • Adalimumab should only be continued in patients who have responded during the first 8 weeks of therapy
  • Some patients who have not responded by week 4 (induction period) may benefit from continued maintenance therapy through week 12. Available data suggest that the clinical response is usually achieved at week 4 of treatment. Continued therapy should be carefully reconsidered in a patient not responding within this time period.

During maintenance treatment, corticosteroids may be tapered in accordance with clinical practice guidelines.

SC: subcutaneous injection; EOW: every other week.

* The use of adalimumab in Crohn’s Disease has been evaluated up to one year in controlled clinical studies. In open-label studies, 510/1,594 patients were evaluated for three years, and 118/1,594 patients for at least five years.
For full dosing and administration information, please see the Product Monograph.
80 mg format currently unavailable in Canada.5

 


 

HYRIMOZ® DOSING FOR INDICATIONS IN DERMATOLOGY1

Hidradenitis Suppurativa*

Recommended induction dose:

  • 160 mg SC at week 0
    • Can be given in one day (four 40 mg injections) or split over two consecutive days (two 40 mg injections each day)
  • 80 mg SC at week 2
    • Given as two 40 mg injections in one day

Recommended maintenance dose:

  • 40 mg every other week beginning at week 4
  • In patients without any benefit after 12 weeks of treatment, continued therapy should be reconsidered.

Plaque Psoriasis

Recommended initial dose: 80 mg SC:

  • Two 40 mg injections
  • Followed by 40 mg SC given EOW starting one week after the initial dose
  • Continued therapy beyond 16 weeks should be carefully reconsidered in a patient not responding within this time period.
SC: subcutaneous injection; EOW: every other week.

* Antibiotics may be continued during treatment with HYRIMOZ® if necessary.
For full dosing and administration information, please see the Product Monograph.
80 mg format currently unavailable in Canada.5

 


 

HYRIMOZ® DOSING FOR INDICATIONS IN OPHTHALMOLOGY1

Uveitis

  • Recommended initial dose: 80 mg SC*
    • Two 40 mg injections
  • Followed by 40 mg SC given EOW starting one week after the initial dose
SC: subcutaneous injection; EOW: every other week.

* HYRIMOZ® can be initiated in combination with corticosteroids and/or other non-biologic immunomodulatory agents. Corticosteroids may be tapered in accordance with clinical practice starting two weeks after initiating treatment with HYRIMOZ®.

† It is recommended that the benefit and risk of continued long-term treatment should be evaluated on a yearly basis.
For full dosing and administration information, please see the Product Monograph.
80 mg format currently unavailable in Canada.5

 


 

ADMINISTRATION1

Preparation of HYRIMOZ® using the single-use prefilled syringe or single-use prefilled SensoReady® pen:

Before injection, allow HYRIMOZ® to reach room temperature (approximately 15 to 30 minutes). DO NOT remove the needle cap while allowing the prefilled syringe or SensoReady® pen to reach room temperature.

Prior to administration, visually inspect the solution for particulate matter and discoloration. The liquid should be clear and colorless to slightly yellowish. You may see visible little particles, which is normal. DO NOT USE if the liquid is cloudy, discolored, or has large lumps, flakes or colored particles.

Sites for injection include the front of thighs, lower abdomen, but not the area 2 inches around the navel; outer upper arm if caregiver/healthcare professional is giving the injection.

Injection sites should be rotated. New injections should be given at least one inch from an old site and never into areas where the skin is tender, bruised, scaly, red, or hard.

Self-administered injections:

HYRIMOZ® is intended for use under the guidance and supervision of a physician.

Patients may self-inject if their physician determines that it is appropriate and with medical follow-up, as necessary, after proper training in measurement of the correct dose and injection technique.

Patients using the pre-filled syringes should be instructed to inject the full amount in the syringe, according to the directions provided in the patient medication information.

 


 

MISSED DOSE1

Patients who miss a dose of HYRIMOZ® should be advised to inject their dose as soon as they remember, then take the next dose at the regular(ly) scheduled time.

See Product Monograph for full dosing and administration information.
RA: rheumatoid arthritis; JIA: polyarticular juvenile idiopathic arthritis; PsA: psoriatic arthritis; AS: ankylosing spondylitis; CD: Crohn’s disease; UC: ulcerative colitis; HS: Hidradenitis Suppurativa; PsO: plaque psoriasis; NIU: non-infectious uveitis.

Safety profile and immunogenicity

 


SAFETY PROFILE ACROSS ALL INDICATIONS


 

HYRIMOZ® DEMONSTRATED A COMPARABLE SAFETY PROFILE TO THE REFERENCE ADALIMUMAB (EU-HUMIRA®)1

The types, frequency and severity of adverse events were comparable between HYRIMOZ® and the reference adalimumab*†

The most serious adverse reactions were:

  • serious infections
  • neurologic events
  • malignancies

 

The most common adverse reaction was injection site reactions.

  • 13% of patients treated with adalimumab developed injection site reactions (erythema and/or itching, hemorrhage, pain or swelling) vs. 7% of patients receiving control treatment.
  • Most injection site reactions were described as mild and generally did not necessitate drug discontinuation.

 


SAFETY PROFILE IN PsO


 

TREATMENT-EMERGENT ADVERSE EVENTS POSSIBLY OR PROBABLY RELATED TO ADALIMUMAB IN ADULTS WITH PsO‡1

TEAEs possibly or probably related to adalimumab that were reported in ≥ 1% of PsO patients in two controlled studies included: injection site reaction (3.0%), headache (2.0%), injection site irritation (1.7%), injection site pain (1.5%), upper respiratory infection (1.2%), arthralgia (1.0%), fatigue (1.0%), and nausea (1.0%).

 


IMMUNOGENICITY PROFILE IN PsO


 

HYRIMOZ® DEMONSTRATED SIMILAR IMMUNOGENICITY WITHIN POSITIVE ADA RESPONDERS TO THE REFERENCE ADALIMUMAB (EU- HUMIRA®)1

ADA response was assessed in 465 PsO patients (HYRIMOZ® n=231 and reference adalimumab* n=234) during treatment period 1 (TP1) (week 1 – 17) and 339 patients during continued treatment§ (HYRIMOZ® n=168 and reference adalimumab* n=171), which lasted to week 51.

The numbers and proportions of patients with positive ADA responses were similar between the HYRIMOZ® and reference adalimumab* and NAbs were detected in similar proportions between groups.

Overall ADA response from Week 1†† to Week 17

  • ADA response TP1 n/N’ (%):
    • Negative = HYRIMOZ® 139/220 (63.2) vs. reference adalimumab* 145/220 (65.9)
    • Positive = HYRIMOZ® 81/220 (36.8) vs. reference adalimumab* 75/220 (34.1)
      • Neutralizing = HYRIMOZ® 65/81 (80.2) vs. reference adalimumab* 60/75 (80.0)

Overall ADA response from Week 1†† to Week 51

  • ADA response continued treatment† n/N’ (%):
    • Negative = HYRIMOZ® 98/160 (61.3) vs. reference adalimumab* 87/159 (54.7)
    • Positive = HYRIMOZ® 62/160 (38.8) vs. reference adalimumab* 72/159 (45.3)
      • Neutralizing = HYRIMOZ® 55/62 (88.7) vs. reference adalimumab* 61/72 (84.7)

 

ADA: anti-drug antibody; EOW: every other week; n: number of patients per treatment group with ADA response; NAbs: neutralizing antibodies; PsO: plaque-type psoriasis; SC: subcutaneous injection; TEAE: Treatment-emergent adverse event; TP1: treatment period 1.

* Reference adalimumab: EU- Humira®

† 553 patients were exposed to at least one dose of adalimumab and 202 patients completed 10 years of study. Of the 553 patients, 23.0% discontinued due to an adverse event. In total, 49% of patients with adalimumab experienced a serious adverse event; 15.7% were considered at least possibly related to the study drug.

‡ Patients were treated with adalimumab 40 mg SC EOW.

§ Continued groups include patients who continued the same treatment throughout the study.

¶ N’=number of patients with evaluable data/N=number of randomized patients.

†† Overall from Week 1 indicates that patients had at least one ADA positive result (recorded as positive) or had consistently negative results (recorded as negative) post-baseline.