CER-001 (Abionyx Pharma), an apolipoprotein A1 (apoA-1)–containing high-density lipoprotein (HDL) mimetic, may help restore kidney function and vision for patients suffering from a rare genetic disorder linked to the progressive development of corneal ring opacities, anemia, splenomegaly, and glomerulopathy, say French researchers.
“We hope that this case report will draw attention to CER-001 as a novel, immediately available treatment option for patients with familial lecithin–cholesterol acyltransferase [LCAT] deficiency,” say Stanislas Faguer, MD, PhD, Hôpital Rangueil, Toulouse, France, and colleagues.
The case report was published in the Annals of Internal Medicine on March 2.
Familial LCAT deficiency is a rare, recessive genetic disease characterized by circulating free cholesterol–rich lipoprotein X (LpX) and very low levels of high-density lipoprotein (HDL). There is currently no approved treatment for the disorder.
The patient was a 37-year-old woman who exhibited chronic kidney disease and who reported blurred vision. Antihypertensive and statin therapy did not halt the decline of the patient’s kidney function, and she was subsequently found to have LCAT deficiency.
Faguer told Medscape Medical News that “the use of CER-001 in this patient was based on the molecular mechanisms that underlie LCAT deficiency–related organ disorders, the ability of CER-001 to reverse transport free cholesterol from tissue in previous in-human studies, and the anti-inflammatory and complement-regulating properties of HDL cholesterol.”
The drug ― which has previously shown some promise in reducing the burden of atherosclerosis in patients with genetic lipid abnormalities ― led to a “clear improvement of the patient’s blurred vision at the end of follow-up” and stabilized her kidney function, the team reports.
This result in combination with “previous data showing the role of apolipoprotein A-1 in the development of corneal clouding and blurred vision lays the groundwork for interventional studies evaluating CER-001 in patients who develop lipid corneal deposits from other causes,” the researchers write.
Faguer, a nephrologist, confirmed to Medscape Medidcal News that “interventional studies evaluating CER-001 in LCAT deficiency or other kidney disorders are indeed being discussed with Abionyx Pharma.”
In a press release, Abionyx said: “The patient, who was about to undergo dialysis due to the rapid decline in renal function, was able to avoid the need for dialysis during her treatment with CER-001. In addition, the patient ― who was suffering from lipid deposits in the corneas ― saw the visual blurring disappear. This clear improvement in visual function is still observed after 1 year of follow-up.”
CER-001 Stabilized Renal Function in the Patient
The patient was initially referred for management of nephrotic syndrome. Blood tests revealed regenerative anemia, chronic kidney disease, and dyslipidemia. HDL cholesterol and apoA-1 levels were very low, and LpX was present.
Cardiovascular screening tests were normal. The patient had splenomegaly and white corneal ring opacities, and she reported blurred vision, especially at night. Further examination identified hyperreflective corneal opacification.
She was found to have mesangial hypertrophy on kidney biopsy. Electron micropscopy revealed numerous pseudomyelin deposits associated with capillary obstruction.
The team determined that the patient was compound heterozygous for two LCAT gene variants.
Treatment with antihypertensive medications and atorvastatin did not halt the decline in the patient’s kidney function. A rapid decrease in estimated glomerular filtration rate (eGFR) had occurred during the preceding 9 months. Treatment with CER-001 was initiated under a compassionate use program.
CER-001 was given intravenously at a dosage of 10 mg/kg three times a week for 3 weeks, then twice a week for 3 weeks, then once a week for 3 weeks. Thereafter, the dosage was increased to 20 mg/kg/wk for 6 weeks to reach the weekly dosage that caused the patient’s eGFR to stabilize.
During 5 months of treatment with the drug and 6 months of follow-up, her eGFR stabilized, and her vision normalized. There was no recurrence of blurred vision.
The splenomegaly was unaffected, and LpX was still detectable. However, no adverse effects were observed. No other treatment was introduced. The team says that the “stabilization of renal function was due to administration of CER-001.”
“We hope that this case report will draw attention to CER-001 as a novel, immediately available treatment option for patients with familial LCAT deficiency and that this will provide further data for the use of CER-001 in this disorder,” the researchers say.
They suggest that the effects of CER-001 on renal progression should be assessed in more common proteinuric diseases, including diabetic nephropathy or extramembranous glomerulonephritis (two diseases characterized by a reduction in local LCAT activity, glomerular lipid deposits, and inflammatory processes), or other nephropathies related to lipid deposits.
“These positive clinical data demonstrate that CER-001 prevented significantly kidney function decline,” Faguer commented in the Abionyx press release. “ApoA-I containing HDL mimetic CER-001 is the first treatment that has proven its ability to slow the progression of renal failure and reduce visual discomfort secondary to corneal lipid deposits in a patient” with a familial lipid disorder.
“We look forward to conducting new clinical studies of CER-001 to assess its ability to improve the prognosis of other orphan or common kidney diseases for which no effective treatment is currently available,” he adds
A Role for CER-001 for Those Who Develop Corneal Deposits From Other Causes?
“The clear improvement of the patient’s blurred vision at the end of follow-up and previous data showing the role of apoA-1 in the development of corneal clouding and blurred vision lays the groundwork for interventional studies evaluating CER-001 in patients who develop lipid corneal deposits from other causes (such as secondary lipid keratopathy or inherited corneal dystrophy),” the researchers add.
Funding for the study has not been disclosed. CER-001 was provided by Abyonyx Pharma. Fageur reports relationships with VIFOR Pharma and ASAHI.
Ann Intern Med. Published online March 2, 2021. Abstract