For many patients, certain treatments can be expensive, invasive, or difficult to access. But it doesn’t have to be this way. According to aHUS News, researchers are running two separate Phase 3 clinical trials to explore the safety, efficacy, and tolerability of crovalimab (RG6107) for patients of all ages with atypical hemolytic uremic syndrome (aHUS). As this investigational therapy is self-injectable, it would offer patients more control over their health.

Crovalimab

According to pharmaceutical company Roche, crovalimab is:

a humanised complement inhibitor C5 monoclonal antibody discovered by Chugai using recycling antibody technology. By blocking the cleavage of C5 to C5a and C5b, it is expected to inhibit complement activation, which is the cause of a number of diseases.

Outside of aHUS, Roche is also evaluating crovalimab as a potential treatment for patients with paroxysmal nocturnal hemoglobinuria (PNH). This treatment is self-injectable, which would allow patients to care for themselves at home. In patients with aHUS, the complement system is overactive, causing health issues. Crovalimab works to manage complement activation, stop the destruction of small blood vessels, and prevent blood clot formation and organ damage. Although it works similarly to other complement inhibitors, such as Ultomiris, crovalimab allows overcomes treatment resistance in patients with certain genetic mutations.

Crovalimab Clinical Trials

In an ongoing Phase 1/2 clinical trial, researchers determined that crovalimab was both safe and effective in inhibiting C5 activity in healthy volunteers and patients with PNH. Although some side effects did occur, these manifested in mild or moderate skin reactions, which later resolved. The study also showed that treatment was effective when given weekly, bi-weekly (every other week), or monthly, allowing a range of potential treatment options.

Moving forward, researchers will evaluate crovalimab in patients with aHUS within the Phase 3 COMMUTE-a and Phase 3 COMMUTE-p trials. During the trials, researchers seek to understand the safety, efficacy, tolerability, and pharmacokinetic and pharmacodynamic properties of crovalimab. Patients ages 12+ are able to enroll in COMMUTE-a, which will enroll 90 patients. Alternately, 35 patients aged 17 or younger will enroll in COMMUTE-p. Patients will be split into 3 groups:

• Those who discontinued treatment with C5 inhibitors or those with a C5 genetic mutation
• Patients previously untreated with complement inhibitors
• Previously treated with another C5 inhibitor who chose to switch treatments

In both trials, patients will receive an initial crovalimab dose in the bloodstream. Next, for a period of up to 8 years, patients will receive subcutaneous injections once weekly for 5 weeks, then once weekly for 4 weeks. Ultimately, researchers seek to understand:

• How many patients achieve a complete thrombotic microangiopathy response (by 25 weeks)
  • Note: This means whether platelet levels are normalized, whether creatinine levels change, and how much lactate dehydrogenase is in the blood.
• Whether crovalimab treatment improves kidney function or fatigue
• If patients develop antibodies against crovalimab treatment

Atypical Hemolytic Uremic Syndrome (aHUS)

Atypical hemolytic uremic syndrome (aHUS) is a rare disease which negatively impacts kidney function. There are multiple genetic mutations associated with aHUS, such as THBD, CFI, CFB, and DGKE. However, these genes do not directly cause aHUS, but rather increase the predisposition for developing aHUS. These genes, in conjunction with pregnancy, certain chronic diseases or medications, viral or bacterial infections, or organ transplantation can spur aHUS to develop. In patients with aHUS, abnormal blood clots form in small blood vessels within the kidneys. If these blood clots restrict or block blood flow, it can cause serious issues. Typically, aHUS affects females more than males, often because of pregnancy. Symptoms include:

• Fatigue
• Lethargy
• Irritability
• Headache
• Double vision
• Pulmonary edema
• Proteinuria (excess protein in the urine)
• Thrombocytopenia (low platelet count)
• Hemolytic anemia (low red blood cell count due to red blood cell destruction)
• Bloody urine
• Organ damage (brain, liver, lungs)
• Cardiomyopathy
• High blood pressure
• Acute kidney failure