TOULOUSE, France—ABIONYX Pharma has reported positive clinical results from CER-001 in familial lecithin–cholesterol acyltransferase (LCAT) deficiency, an ultra-rare kidney disease. A study reporting this research has been published in the Annals of Internal Medicine.
“These positive clinical data published in one of the most cited medical journals prove the efficacy of our bioproduct and reveal the relevant repositioning of CER-001 in a severe renal indication where there has been no breakthrough therapeutic innovation in the last 10 years,” noted Cyrille Tupin, managing director of ABIONYX Pharma. “This represents an important step forward in the clinical development of CER-001.”
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 treatment with CER-001. The patient was additionally suffering from lipid deposits in the corneas, and after CER-001 treatment saw the visual blurring disappear. This clear improvement in visual function was still observed after one year of follow-up.
The patient had inherited mutations in the LCAT gene, had developed glomerulopathy and corneal lipid deposits, and displayed very low circulating levels of high-density lipoprotein (HDL) and ApoA1. The patient was treated with CER-001, an ApoA1-containing HDL mimetic, to help in preventing rapidly progressive kidney failure. CER-001 was given intravenously at a dose of 10 mg/kg three times per week for 3 weeks, twice a week for 3 weeks, and then once a week for 3 weeks. Thereafter, the dose was increased to 20 mg/kg/week for 6 weeks to reach the weekly dose that stabilized eGFR.
Whereas eGFR rapidly decreased from 41 to 19 mL/min/1.73 m2 during the nine months that preceded the start of CER-001, eGFR only decreased from 19 to 17 mL/min/1.73 m2 during the 11 months following the introduction of treatment. Urinary protein-to-creatinine ratio (uPCr) decreased from 7 to 0.25 g/g at day 10, with undetectable albuminuria at that time, but returned to initial values thereafter. However, 2/3 nephrotic syndrome disappeared, with serum albumin increased from 29 to 37 g/L during the treatment period and the follow-up.
“I would like to warmly thank Professor Faguer for his major contribution and all the teams at the Toulouse University Hospital for their continued collaboration. We are very grateful to the French National Agency for Drug Safety for accepting Prof. Faguer’s request for ATUn [Temporary Authorization for Use], as well as to the patient who fully supported the therapeutic project that led to this discovery,” added Tupin. “The ABIONYX team continues to explore other potential medical benefits associated with CER-001 … We are committed to advancing the clinical development of the mimetic HDL as quickly and safely as possible while investigating new indications in ophthalmology so that we can help address new rare or orphan diseases with no existing treatment.”
The study points out that CER-001 effects on renal progression should be assessed in more common proteinuric diseases — including diabetic nephropathy or extra-membranous glomerulonephritis, or other nephropathies related to lipid deposits. The study also underscored the positive extra-renal clinical results like the disappearance of visual blurring secondary to corneal deposits, and the longevity of this improvement in visual function.
The improvement of blurred vision at the end of the follow-up suggests that the anti-inflammatory properties and/or the increase in the reverse cholesterol transport of CER-001 can improve vision in familial LCAT deficiency (FLD) patients. This finding, and previous data showing the role of ApoA1 in the development of corneal clouding and blurring vision, could pave the way to interventional studies testing CER-001 in patients developing lipid corneal deposits from other pathologies like secondary lipid keratopathy or inherited corneal dystrophy.
“These positive clinical data demonstrate that CER-001 prevented significantly kidney function decline. ApoA1 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 FLD,” stated Prof. Stanislas Faguer, nephrologist in the Department of Nephrology and Organ Transplantation Reference Center for Rare Kidney Diseases, Hospital Rangueil, CHU Toulouse. “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.”