EFFICACY & SAFETY

OXLUMO™ (lumasiran) significantly reduced urinary oxalate (UOx)1

ILLUMINATE-A: The largest interventional study in primary hyperoxaluria type 1 (PH1)1

ILLUMINATE-A is a multicenter, phase 3, randomized, placebo-controlled trial that had a 6-month double-blind period. The trial included adults and children aged ≥6 years with eGFR ≥30 mL/min/1.73 m2 (N=39).1

eGFR, estimated glomerular filtration rate.

ILLUMINATE-A study design1

6-MONTH double-blind period. Patients continued on their standard-of-care regimen during this period.*

2:1 RANDOMIZATION

n=26 

OXLUMO (3 mg/kg subcutaneous injection)

n=13 

Placebo (subcutaneous injection)

DOSING

3 MONTHLY STARTING DOSES followed by ONGOING DOSES, which were administered once every 3 months beginning one month after last starting dose

Including hyperhydration, crystallization inhibitors, and/or pyridoxine therapy.

Selected baseline characteristics1

  • Broad age range between 6 and 61 years (median: 15 years)1
  • Significantly elevated baseline 24-hour UOx level corrected for BSA (median: 153.1 mg [1.7 mmol])1
  • 33% of patients had eGFR ≥90 mL/min/1.73 m2; 49% of patients had eGFR 60 to <90 mL/min/1.73 m2; 18% of patients had eGFR 30 to <60 mL/min/1.73 m2
  • 56% of patients were receiving pyridoxine (vitamin B6) at baseline2

PRIMARY ENDPOINT1:

  • Percent reduction from baseline in 24-hour urinary oxalate (UOx) excretion averaged over months 3 through 6, corrected for body surface area (BSA)

SECONDARY ENDPOINTS1:

  • Absolute reduction from baseline in 24-hour UOx excretion averaged over months 3 through 6, corrected for BSA
  • Proportion of patients with normal or near-normal 24-hour UOx levels (at or below 1.5 x ULN) at month 6
  • Proportion of patients with normal 24-hour UOx levels (at or below ULN) at month 6

1.5 x ULN, ≤69.4 mg/24 h/1.73 m2 (≤0.771 mmol/24 h/1.73 m2); ULN, ≤46.3 mg/24 h/1.73 m2 (≤0.514 mmol/24 h/1.73 m2). ULN, upper limit of normal.

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95% (37/39) of patients entered into an ongoing 54-month extension period where all patients received OXLUMO.2

Treatment with OXLUMO resulted in rapid, powerful, and sustained urinary oxalate reduction1

In patients who received OXLUMO, a rapid onset of reduction in 24-hour UOx was observed within 2 weeks, with
maximal reduction reached by the end of month 2.1

Reduction in 24-hour UOx from baseline*,1,2

×
24-hour UOx corrected for BSA
(mg/24 h/1.73 m2)
OXLUMO (↓65%)
PLACEBO (↓12%)
1.5 X ULN
ULN
  • Number of Patients PLACEBO n =            13
  • 13
  • 12
  • 13
  • 13
  • 13
  • 13
  • OXLUMO n =            26
  • 24
  • 26
  • 24
  • 23
  • 25
  • 25

 

PRIMARY ENDPOINT

Reduction in 24-hour UOx excretion from baseline to month 6 for OXLUMO compared to placebo

(P<0.0001; 95% CI: 45%, 62%)‡,1

SECONDARY ENDPOINT

Treatment with OXLUMO led to a 112 mg/24 h/1.73 m2 (1.24 mmol/24 h/1.73 m2) reduction in 24-hour UOx levels from baseline to month 6 compared with 24 mg/24 h/1.73 m2 (0.27 mmol/24 h/1.73 m2) for placebo.‡,2

Mean ± standard error of mean of actual observed values.

1.5 x ULN, ≤69.4 mg/24 h/1.73 m2 (0.771 mmol/24 h/1.73 m2); ULN, ≤46.3 mg/24 h/1.73 m2 (0.514 mmol/24 h/1.73 m2).

Least squares mean reduction averaged over months 3 through 6, corrected for BSA.1

BSA, body surface area; CI, confidence interval; ULN, upper limit of normal; UOx, urinary oxalate.

Treatment with OXLUMO showed a rapid lowering of urinary oxalate within 2 weeks. Maximal reduction in 24-hour UOx was reached by the end of month 2.1

Most PH1 patients treated with OXLUMO had 24-hour UOx reduced to normal or near-normal levels (≤1.5 x ULN) at month 61,2

84 OF OXLUMO
PATIENTS
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Versus
0 OF PLACEBO
PATIENTS
  • 84% (21/25) of patients treated with OXLUMO had 24-hr UOx corrected for BSA at or below 1.5 x ULN (≤69.4 [≤0.771 mmol])§,||
  • 52% (13/25) of patients treated with OXLUMO had 24-hr UOx corrected for BSA at or below ULN (≤46.3 [≤0.514 mmol])¶,||
  • 0% (0/13) of patients receiving placebo had levels at or below 1.5 x ULN**

95% CI: 64%, 95%; P<0.0001 vs placebo.

Corrected for BSA.

95% CI: 31%, 72%; P=0.0001 vs placebo.

95% CI: 0%, 30%.

See below for information about the safety profile of OXLUMO

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ILLUMINATE-B studied OXLUMO in infants and young children with PH11

The multicenter phase 3, single-arm, open-label trial includes patients aged <6 years with eGFR >45 mL/min/1.73 m2 (normal serum creatinine was used for patients aged <12 months).1,2

ILLUMINATE-B study design1,2

SINGLE-ARM, OPEN-LABEL TRIAL (N=18)

OXLUMO (3 mg/kg or 6 mg/kg subcutaneous injection, based on weight. Patients continued receiving their standard-of-care regimen during the trial.*)

DOSING

3 MONTHLY STARTING DOSES OF:

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3 mg/kg (≥20 kg) 

6 mg/kg (<20 kg) 

BEGINNING ONE MONTH AFTER LAST STARTING DOSE, ALL PATIENTS RECEIVED ONGOING DOSES:

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Monthly doses of 3 mg/kg (patients <10 kg)
OR
Quarterly doses of 3 mg/kg (≥20 kg) or 6 mg/kg (≥10 kg to <20 kg)

6-MONTH primary analysis period. Patients continued receiving their standard-of-care regimen during the trial.* Patients subsequently entered into an ongoing 54-month extension period. 

Including hyperhydration, crystallization inhibitors, and/or pyridoxine therapy.
 

Selected baseline characteristics:

  • Median age at first dose: 47 months (range: 4 to 74 months)1
  • Median spot UOx:creatinine ratio at baseline: 0.37 mg/mg (0.47 mmol/mmol)1

ILLUMINATE-B: OXLUMO efficacy results in infants and young children (<6 years)1

PRIMARY ENDPOINT (interim analysis, n=16/18) Percent reduction from baseline in spot UOx:creatinine ratio averaged over months 3 through 6††,1

Reduction from baseline to month 6 in spot UOx:creatinine ratio‡‡
(95% CI: 65%, 77%)

Analysis of the primary endpoint included the first 16 patients who received 6 months of treatment with OXLUMO.1

Percent reduction from baseline in spot UOx:creatinine ratio averaged over months 3 through 6.1

Analysis of the primary endpoint included the first 16 patients who received 6 months of treatment with OXLUMO.1

Percent reduction from baseline in spot UOx:creatinine ratio averaged over months 3 through 6.1

OXLUMO safety profile

The safety profile of OXLUMO was evaluated in infants, children, and adults with PH11

OXLUMO has been studied in 77 patients with PH1, including 56 pediatric patients.1

Patients ranged in age from 4 months to 61 years at first dose, and received OXLUMO for a median of 9.1 months (range: 1.9 to 21.7 months).

  • 58 patients were treated for at least 6 months, and 18 patients for at least 12 months

In ILLUMINATE-A (N=39), the most common adverse reaction was injection site reaction (ISR).1

  • ISR occurred throughout the study period and included erythema, pain, pruritus, and swelling
  • These symptoms were generally mild and resolved within one day of the injection and did not lead to discontinuation of treatment

Adverse reactions in ILLUMINATE-A reported in ≥10% of patients treated with OXLUMO and occurring ≥5% more frequently than in patients treated with placebo during the 6-month double-blind period

ADVERSE REACTION

Injection site reaction

Abdominal paina

OXLUMO (n=26) n (%)

10 (38)

4 (15)

PLACEBO (n=13) n (%)

0 (0)

1 (8)

aGrouped term includes abdominal pain, abdominal pain upper, abdominal pain lower, and abdominal discomfort.
 

In the 6-month analysis period of ILLUMINATE-A, all adverse events in both the group treated with OXLUMO and the group treated with placebo were mild or moderate in severity. There were no serious adverse events.2

In ILLUMINATE-B (N=18), the safety profile observed was similar to that seen in ILLUMINATE-A.1

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References: 1. OXLUMO (lumasiran) [Package Insert]. Cambridge, MA. Alnylam Pharmaceuticals, Inc. 2. Garrelfs SF, Frishberg Y, Hulton SA, et al. ILLUMINATE-A, a phase 3 study of lumasiran, an investigational RNAi therapeutic, in children and adults with primary hyperoxaluria type 1 (PH1). Presented at: 57th Congress of the European Renal Association–European Dialysis and Transplant Association (ERA-EDTA); June 6-9, 2020; Milan, Italy (virtual).

IMPORTANT SAFETY INFORMATION

Adverse Reactions
The most common adverse reaction that occurred in patients treated with OXLUMO™ (lumasiran) was injection site reaction (38%). Symptoms included erythema, pain, pruritus, and swelling.

Pregnancy and Lactation
No data are available on the use of OXLUMO in pregnant women. No data are available on the presence of OXLUMO in human milk or its effects on breastfed infants or milk production. Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for OXLUMO and any potential adverse effects on the breastfed child from OXLUMO or the underlying maternal condition.

INDICATION

OXLUMO is indicated for the treatment of primary hyperoxaluria type 1 (PH1) to lower urinary oxalate levels in children and adults.

For additional information about OXLUMO, please see the full Prescribing Information.