By Counterforce Health Team —

From Gene to Relief: The Science and Promise of Oxlumo for PH1

Primary hyperoxaluria type 1 (PH1) is a rare genetic disorder that can lead to kidney stones, kidney damage, and even kidney failure. For many years, treatment options were limited to managing symptoms or, in severe cases, undergoing a liver or kidney transplant.

In 2020, the approval of Oxlumo® (lumasiran) marked a major medical milestone — the first therapy specifically designed to target the root cause of PH1. Using cutting-edge RNA interference (RNAi) technology, Oxlumo helps reduce the overproduction of oxalate, offering patients a safer, more effective way to control their disease.

What Is Oxlumo?

Oxlumo (lumasiran) is a prescription medication used to treat primary hyperoxaluria type 1 (PH1) in both children and adults.

It is the first and only FDA-approved therapy that directly addresses the underlying genetic cause of PH1 — a rare condition in which the liver overproduces oxalate, leading to dangerous crystal buildup in the kidneys and urinary tract.

Oxlumo is given as a subcutaneous (under the skin) injection, typically administered once a month at first and then less frequently as maintenance therapy.

Understanding Primary Hyperoxaluria Type 1

What Causes PH1

PH1 is caused by a mutation in the AGXT gene, which leads to a deficiency or malfunction of an enzyme called alanine:glyoxylate aminotransferase (AGT). This enzyme normally helps the liver convert glyoxylate into a harmless compound.

When AGT doesn’t work properly, glyoxylate builds up and is converted into oxalate, a waste product that the body cannot break down. The excess oxalate combines with calcium to form crystals and kidney stones, which can damage the kidneys over time.

Common Symptoms of PH1

  • Recurrent kidney stones or urinary tract infections
  • Pain in the back or sides
  • Blood in the urine
  • Fatigue from kidney dysfunction
  • In severe cases, end-stage kidney disease (ESKD) or systemic oxalosis, where oxalate deposits in bones, eyes, heart, or skin

Without treatment, PH1 can cause serious long-term complications and require dialysis or organ transplantation.

How Oxlumo Works

Oxlumo uses RNA interference (RNAi) technology — a Nobel Prize-winning scientific breakthrough that allows for “gene silencing” of specific disease-causing proteins.

Here’s how Oxlumo helps patients with PH1:

  1. The active ingredient, lumasiran, is a small interfering RNA (siRNA) molecule.
  2. It targets the messenger RNA (mRNA) that carries instructions for making glycolate oxidase (GO) — an enzyme in the liver involved in the oxalate production pathway.
  3. By reducing GO levels, Oxlumo decreases the amount of glyoxylate available for conversion into oxalate.
  4. As a result, the liver produces less oxalate, leading to lower oxalate levels in the blood and urine.

In short, Oxlumo helps slow or stop oxalate overproduction at its source, protecting the kidneys from further damage.

Clinical Evidence and Approval

Oxlumo’s approval was supported by the ILLUMINATE clinical trial program, which included both children and adults with PH1.

Key findings:

  • Significant reduction in urinary oxalate levels: After six months, patients treated with Oxlumo had up to 65–70% lower urinary oxalate compared to baseline.
  • Rapid and sustained effect: Oxalate levels began to drop within weeks of the first dose and remained low with ongoing treatment.
  • Improved clinical outcomes: Many patients had fewer kidney stone events and stabilized or improved kidney function over time.

These results established Oxlumo as the first effective, disease-modifying therapy for PH1.

How Oxlumo Is Administered

  • Route: Subcutaneous injection (under the skin)
  • Dosing schedule:
    • Initial phase: One dose once monthly for three months
    • Maintenance phase: One dose every three months thereafter
  • Dosing amount: Based on body weight (your healthcare provider calculates the appropriate dose)

Oxlumo may be given by a healthcare professional or, for some patients, administered at home by a trained caregiver.

Benefits of Oxlumo

Oxlumo offers several meaningful benefits for people living with PH1:

  • Lowers urinary and plasma oxalate levels — reducing the root cause of kidney damage
  • May help prevent new kidney stones and slow progression of kidney disease
  • Reduces risk of systemic oxalosis (oxalate buildup in other organs)
  • Safe for all ages, including infants and children
  • Noninvasive alternative to organ transplantation or lifelong dialysis

For many patients, Oxlumo has transformed PH1 from a progressive, life-threatening condition into one that can be effectively managed with regular injections.

Possible Side Effects

Oxlumo is generally well tolerated. The most common side effects reported in clinical studies include:

  • Injection-site reactions: redness, pain, itching, or swelling
  • Abdominal pain
  • Headache
  • Fatigue

These reactions are typically mild to moderate and resolve on their own.

Less common but important considerations:

  • Liver function: Because Oxlumo acts in the liver, healthcare providers may monitor liver enzyme levels during treatment.
  • Allergic reactions: Rarely, patients may experience hypersensitivity reactions such as rash or swelling; medical attention should be sought immediately if this occurs.

Monitoring and Ongoing Care

Patients on Oxlumo will have regular follow-up visits to:

  • Measure urinary and plasma oxalate levels to assess treatment response
  • Monitor kidney function through lab tests
  • Track growth and development in pediatric patients
  • Adjust the dosage if necessary based on body weight changes

Your healthcare provider will design a personalized monitoring plan to ensure the treatment remains effective and safe over time.

Who Can Receive Oxlumo

Oxlumo is approved for the treatment of primary hyperoxaluria type 1 (PH1) in patients of all ages — from infants to adults.

It is not approved for other forms of hyperoxaluria (types 2 or 3) or for patients whose oxalate buildup is caused by non-genetic factors.

Practical Considerations

  • Storage: Oxlumo must be kept refrigerated until ready for use.
  • Scheduling: Consistent dosing is important — missing doses can reduce effectiveness.
  • Lifestyle: Patients should continue to stay hydrated and follow any dietary or fluid intake guidance from their healthcare provider.
  • Support programs: Financial assistance and educational resources are available through patient support organizations and manufacturer programs.

The Bottom Line

Oxlumo (lumasiran) represents a revolutionary advance in the treatment of primary hyperoxaluria type 1. By using RNA interference to reduce oxalate production at its source, it helps protect the kidneys, prevent complications, and improve quality of life for people living with this rare disease.

For patients and families affected by PH1, Oxlumo offers something that was once out of reach — hope for long-term disease control and a more normal life.