ARCALYST (rilonacept) is proven to treat recurrent pericarditis and significantly reduce the risk of pericarditis episodes

Targeted Mechanism

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

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

 

MOA-graphic-updated

 

 

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 below and learn about the ARCALYST mechanism of action

PHASE 3 RHAPSODY TRIAL

ARCALYST met the primary and all major secondary endpoints in the RHAPSODY pivotal trial.1,2

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 tapering of standard therapies

Single-Blind • Run-In Period
GOAL

Assess time to treatment response and time to ARCALYST monotherapy

Upon enrollment patients were:

  • Started on a loading dose of ARCALYST
  • Tapered off standard therapies to achieve ARCALYST monotherapy by 10 weeks

Randomized Withdrawal
Event Driven

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 treatment 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 were offered participation in the long-term extension treatment period.

All eligible patients received open-label ARCALYST.

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

A total of 86 patients (mean age 45 years [range 13-78], 57% females) with symptomatic pericarditis recurrence were enrolled and received trial treatment.1

Of these, 73 (85%) had a diagnosis of idiopathic pericarditis, the remainder being post cardiac injury. The mean duration of disease was 2.4 years with a mean number of 4.4 pericarditis events per year including the qualifying pericarditis event (0-10 point NRS ≥4 and CRP ≥1 mg/dL). Mean qualifying NRS pain score was 6.2, and mean qualifying CRP level was 6.2 mg/dL.1

REDUCTION IN RISK OF FUTURE FLARES

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 ARCALYST Probability of Number of Pericarditis Recurrence (%)
Only 7% (2 of 30) of patients treated with ARCALYST had a recurrence during the randomized withdrawal period.1

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

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

74% (23 of 31) of 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).

RESOLUTION OF EPISODES

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 treatment response.*1,2

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

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

*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).

FURTHER PROOF

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 monotherapy.1,3

48% (41 of 86) 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 monotherapy 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).

 

 

 

 

ARCALYST provides patients with a new choice. 

98%
of patients chose to continue
treatment with ARCALYST in the long-term extension (LTE) trial.1,3