The generic name for the prescription drug Oxlumo is lumasiran. It is a unique and targeted medication used to treat Primary Hyperoxaluria type 1 (PH1), a rare genetic disorder. As a pioneering treatment, its development represents a significant step forward in managing a disease that previously relied on supportive care, dialysis, or transplants. Lumasiran's mechanism of action, rooted in advanced genetic science, offers a way to address the root cause of PH1 rather than just managing the symptoms.
What is Lumasiran (Oxlumo)?
Lumasiran, also known by its brand name Oxlumo, is a small interfering ribonucleic acid (siRNA) agent developed by Alnylam Pharmaceuticals. It received FDA approval in November 2020 for the treatment of PH1 in both pediatric and adult patients. PH1 is an ultra-rare, progressive genetic condition causing the liver to overproduce oxalate. Normally, the AGT enzyme processes glyoxylate, preventing excess oxalate. However, in PH1 patients with an AGXT gene mutation, this enzyme is deficient, leading to a buildup of calcium oxalate crystals in the kidneys and other organs.
Mechanism of Action
Lumasiran utilizes RNA interference (RNAi) to regulate gene expression. It specifically targets the liver to silence the messenger RNA (mRNA) of the HAO1 gene, which is responsible for producing glycolate oxidase (GO). By reducing GO production, lumasiran effectively lowers the levels of glyoxylate, the precursor to oxalate, thereby decreasing harmful oxalate in urine and plasma. This mechanism works regardless of the specific AGXT gene mutation causing PH1.
The Purpose of Lumasiran
Prior to lumasiran, PH1 treatments were limited, including high fluid intake, pyridoxine for some patients, and potentially liver and/or kidney transplantation. Dialysis was often necessary for end-stage kidney disease (ESKD) but often insufficient. Lumasiran offers a targeted, disease-modifying therapy by addressing the underlying metabolic defect.
Symptoms of Primary Hyperoxaluria Type 1
PH1 symptoms vary but often involve the urinary tract due to calcium oxalate crystal accumulation. Complications include:
- Recurrent Kidney Stones: Requiring repeated procedures.
- Nephrocalcinosis: Crystal deposits in kidney tissue causing damage.
- Progressive Chronic Kidney Disease: Gradual decline in kidney function, potentially leading to ESKD.
- Systemic Oxalosis: In advanced ESKD, high blood oxalate leads to crystal deposits in other organs.
Lumasiran vs. Nedosiran: A Comparison
Nedosiran (Rivfloza) is another RNAi therapeutic for PH1, also recently approved. Both are targeted RNAi therapies but act on different enzymes involved in oxalate production.
| Feature | Lumasiran (Oxlumo) | Nedosiran (Rivfloza) |
|---|---|---|
| Drug Class | Small Interfering RNA (siRNA) | Small Interfering RNA (siRNA) |
| Mechanism | Targets and silences HAO1 mRNA to reduce glycolate oxidase | Targets and silences LDH mRNA to reduce lactate dehydrogenase |
| Target Organ | Liver | Liver |
| Indication | PH1, to lower urinary and plasma oxalate | PH1, to lower urinary and plasma oxalate |
| Administration | Subcutaneous injection | Subcutaneous injection |
| Dosing | Monthly (loading) then quarterly for ≥20kg; monthly for <10kg | Monthly (loading) then quarterly |
Is a Generic Oxlumo Available?
No, a generic version of Oxlumo is not currently available. Lumasiran is a relatively new drug approved in late 2020. New brand-name medications are protected by patents and market exclusivity, preventing generic production until these expire. FDA records indicate exclusivity for lumasiran extends into 2027 and possibly beyond for specific uses. Therefore, Oxlumo is currently only available as the brand-name product from Alnylam Pharmaceuticals.
Considerations for Lumasiran Treatment
Lumasiran is administered via subcutaneous injection by a healthcare professional. Dosing depends on weight, with a loading and maintenance phase. Specific instructions exist for patients on hemodialysis. The most common side effect is injection site reactions, typically mild and temporary. Abdominal pain is another potential side effect. Treatment should be managed by specialists experienced in PH1 due to its rarity.
Common Side Effects of Lumasiran
- Injection site reactions (pain, redness, swelling, itching, bruising)
- Abdominal pain
Conclusion
The generic name for Oxlumo is lumasiran, a liver-targeted RNAi therapeutic that has significantly improved the treatment of Primary Hyperoxaluria type 1. By addressing the genetic cause and reducing oxalate overproduction, lumasiran offers improved long-term outcomes. While no generic is currently available, it represents a major advancement in treating this rare and devastating condition. Patients should consult their healthcare team to determine if lumasiran is appropriate.
