Tracy McGregor, MD MSCI Alnylam Pharmaceuticals Cambridge, Massachusetts

Lumasiran Study Offers Hope For Patients with Debilitating Primary Hyperoxaluria Interview with:

Tracy McGregor, MD MSCI Alnylam Pharmaceuticals Cambridge, Massachusetts

Dr. McGregor

Tracy McGregor, MD MSCI
Alnylam Pharmaceuticals
Cambridge, Massachusetts What is the background for this study?

  • Lumasiran is an investigational RNA interference (RNAi) therapeutic in development for the treatment of primary hyperoxaluria type 1 (PH1). PH1 is a rare life-threatening disease in which a enzymatic deficiency in the liver results in pathologic overproduction of oxalate, often leading to recurrent kidney stones and a progressive decline in kidney function, which typically culminates in end-stage renal disease (ESRD).Patients with ESRD are at a risk of systemic oxalosis, with oxalate depositing throughout the body, including the eyes, skin, bones, and the heart. Complications associated with ESRD and/or systemic oxalosis can be fatal. For patients with ESRD treatment options are limited and include intensive dialysis as a bridge to a dual liver/kidney transplant, highlighting the unmet need for new treatment options. What are the main findings?

Results from the OLE study being presented at the ASN Annual Meeting are being reported as of the data cut-off date of September 12, 2019. Key findings are outlined below:

    • Lumasiran demonstrated a 76 percent mean maximal reduction (range: 43-91 percent) in urinary oxalate excretion relative to Phase 1/2 baseline values in all cohorts (N=19)*.
    • All patients achieved a urinary oxalate level at or below 1.5 times the upper limit of normal (1.5 x ULN = 0.69 mmoL/24hr/1.73m2)
    • 68 percent of patients achieved a urinary oxalate level within the normal range (less than 0.46 mmol/24hr/1.73m2).
    • Patients also experienced an 82 percent mean maximal reduction in urinary oxalate:creatinine ratio (range: 62-94 percent) after lumasiran dosing across all cohorts (N=20).
    • Adverse events were reported in 19/20 (95 percent) patients; a majority were mild in severity and assessed as unrelated to study drug by the investigators. What should readers take away from your report? 

Response: Overall, we are encouraged by the positive results from our Phase 2 OLE study and believe that lumasiran has the potential to address the profound unmet medical need that PH1 represents. What recommendations do you have for future research as a result of this work? 

  • The Phase 2 OLE study of lumasiran is ongoing and we look forward to presenting additional results.
  • In addition, during the ASN Annual Meeting, Alnylam will announce initiation of the ILLUMINATE-C Phase 3 study. ILLUMINATE-C is designed to assess the safety and efficacy of lumasiran in PH1 patients with advanced renal disease, including patients on dialysis. This study complements our comprehensive clinical development plan for lumasiran, led by our ILLUMINATE-A pivotal study in patients with preserved renal function, with results expected later this year, and our ILLUMINATE-B study in young pediatric patients. The ILLUMINATE trials collectively address PH1 patients across the spectrum of age and disease onset and severity. Is there anything else you would like to add?

Response: I encourage readers to learn more about PH1 by visiting Approximately 50% of PH1 patients may be undiagnosed due to the low index of suspicion of PH1 among physicians, which underscores the need to raise awareness. 

Citation: ASN 2019

Interim Results from the Ongoing Phase 2 Open-Label Extension Study of Lumasiran, an Investigational RNA Interference  Therapeutic, in Patients with Primary Hyperoxaluria Type 1



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Last Updated on November 11, 2019 by Marie Benz MD FAAD