An innovative approach with breakthrough results1

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An innovative approach with breakthrough results1

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Targeted Mechanism

ARCALYST specifically targets interleukin-1 alpha (IL-1α) and interleukin-1 beta (IL-1β).1

Targeting these key cytokines blocks the underlying mechanism that drives inflammation in recurrent pericarditis.1

IL-1 receptorARCALYSTIL-1βIL-1α

ARCALYST blocks IL-1 signaling by acting as a soluble decoy receptor that binds both IL-1α and IL-1β and prevents their interaction with cell surface receptors, thus disrupting the cycle of autoinflammation that drives recurrent pericarditis.

Watch the video to learn the key role of IL-1 and view about the ARCALYST mechanism of action.

PHASE 3 RHAPSODY

RHAPSODY is a Phase 3 clinical trial designed to study ARCALYST in recurrent pericarditis.1

See below for the full design of the Phase 3, global, multicenter,
double-blind, placebo-controlled, randomized withdrawal trial
with an open-label extension.1,2

Run-In Period
12 Weeks

Initiation of ARCALYST and transition to monotherapy

Single-Blind • Run-In Period
GOAL

Assess time to treatment response and time to ARCALYST monotherapy

 

SECONDARY ENDPOINT

Proportion of patients achieving a treatment response

Upon enrollment patients were:

  • Started on a loading dose of ARCALYST
  • Tapered off standard therapies to achieve ARCALYST monotherapy
    • Standard therapies included nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine, and corticosteroids (alone or in combination)
  • Monotherapy was achieved in 7.9 weeks

The number of patients taking standard therapies at enrollment were as follows3:

  • NSAIDs: 58
  • Colchicine: 69
  • Corticosteroids: 42

Randomized Withdrawal
Event Driven by Adjudicated Recurrences

Treatment with ARCALYST or placebo

Double-Blind • Placebo-Controlled, Randomized-Withdrawal (RW) Period
Goal

Assess reduction in risk of pericarditis recurrence

 

PRIMARY TRIAL ENDPOINT

Time to pericarditis recurrence
 

Major SECONDARY EFFICACY ENDPOINTS (week 16)
  • Proportion of patients maintaining clinical response
  • Percentage of days with no or minimal pericarditis pain

After randomization, patients were treated with double-blind ARCALYST or placebo in a 1:1 ratio until recurrence of pericarditis or until the end of the study.

  • Blinded ARCALYST
    • 160 mg subcutaneous injection weekly (adults ≥18 years)
    • 2.2 mg/kg subcutaneous injection weekly (adolescents 12-17 years)
  • Blinded placebo subcutaneous injection weekly
  • Eligible patients experiencing a recurrence received bailout ARCALYST

Long-Term Extension
24 Months

Long-term management with ARCALYST

Open-Label, Long-Term Extension Period
GOAL

Assess treatment up to 2 years

 

When the event-driven portion of the trial closed, eligible patients could participate in the open-label long-term extension (LTE) treatment period.

All eligible patients received open-label ARCALYST during the LTE treatment period.

Key inclusion criteria at screening

Diagnosed with recurrent pericarditis (idiopathic or post-cardiac injury)
Presenting with at least a second recurrence of pericarditis
Male or female aged 12 and older
If using NSAIDs, and/or colchicine, and/or corticosteroids, doses remained stable or were not increased for at least 3 days prior to first drug administration
LASTING PREVENTION

ARCALYST is proven to significantly reduce the risk of pericarditis recurrence.  

The primary efficacy endpoint was time to first adjudicated pericarditis recurrence in the randomized withdrawal period.1
 

100 reduction in the risk of recurrent pericarditis (hazard radio: 0.04; p < 0.0001). 1 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 90 80 70 60 50 40 30 Time (weeks) 20 10 0 PLACEBO (n=31) ARCALYST (n=30) Probability of No Pericarditis Recurrence (%)
ARCALYST

2 of 30 patients treated with ARCALYST had a recurrence during the randomized withdrawal period.1

  • The 2 pericarditis recurrences with ARCALYST occurred during temporary interruptions of 1 to 3 weekly doses of ARCALYST.

The median time to recurrence on ARCALYST could not be estimated due to the low number of recurrences.

PLACEBO

23 of 31 patients treated with placebo experienced a recurrence during the randomized withdrawal period.1

The median time to recurrence on placebo was 8.6 weeks (95% CI: 4.0, 11.7).

RAPID RESOLUTION

ARCALYST is shown to provide rapid treatment response.

Secondary endpoints that were assessed during the run-in period.1

In the pivotal trial,
97 %
of patients taking ARCALYST experienced rapid symptom relief* as early as the first dose.1,2
RAPID TREATMENT RESPONSE

During the 12-week run-in period, 77 of 79 patients demonstrated a treatment response.*

  • Median time to treatment response = 5.0 days (95% CI: 4.0, 7.0)
  • Median time to ARCALYST monotherapy = 7.9 weeks
RAPID SYMPTOM RELIEF

During the 12-week run-in period, patients also achieved symptom relief and reduction in inflammation.

  • Median time to pain response = 5.0 days
  • Median time to CRP normalization = 7.0 days

CRP=C-reactive protein; NRS=Numerical Rating Scale (ranging from 0 to 10 and with higher scores indicating greater pain severity).

*Symptom relief or time to treatment response was defined as the time from the first dose to the first day when pericardial pain was NRS ≤2 and CRP ≤0.5 mg/dL (measured within 7 days before or after the pain response).

FREEDOM FROM STEROIDS AND PAIN

Patients treated with ARCALYST were able to
discontinue corticosteroids.

 

 

 

In the Phase 3 RHAPSODY trial run-in period, patients receiving corticosteroids at baseline were effectively transitioned to ARCALYST.1,3

  • Corticosteroids carry the potential risk of side effects that can complicate management4-6
    • Use is associated with the risk of recurrence and a prolonged course of disease5,6
  • Median time to ARCALYST monotherapy was 7.9 weeks1

44.3% (27 of 61) of patients received corticosteroids at baseline.1

  • Each patient treated with corticosteroids at baseline achieved clinical response with ARCALYST monotherapy
  • None of the patients treated with corticosteroids at baseline and randomized to ARCALYST experienced a recurrence while on therapy

Patients treated with ARCALYST experienced minimal or no pericarditis pain.1

Secondary efficacy endpoint was assessed during the randomized withdrawal period.1

Patients reported
92%

of days with no pain
or minimal pain (NRS ≤2).1

 


Compared with 40% for patients on placebo (p<0.0001) at the secondary endpoint assessed at Week 16 of the randomized withdrawal period.

 

 

At week 16 of the randomized withdrawal period:

A majority (81%) maintained a clinical response measured at week 16 of the randomized withdrawal period compared with 20% for placebo (p=0.0002).

 

 

 

 

Patients taking ARCALYST chose to stay on therapy.

99%
of patients chose to continue treatment
in the open-label LTE treatment period.1,3

74 of 75 eligible patients chose to enroll in the ongoing LTE treatment period at the completion of the RW period.