24 May Emerging Treatment Paradigms in Focal Segmental Glomerulosclerosis (FSGS)
Focal segmental glomerulosclerosis (FSGS) is a disease caused by the degeneration of glomeruli, the filtering system of the kidney’s and is caused by factors such as diabetes, lupus, sickle cell disease or use of anabolic steroids. It is characterized by a large amount of proteinuria, nephrotic syndrome, weight gain, high cholesterol levels and edema. This illness can occur without an underlying condition leading to primary focal segmental glomerulosclerosis or due to a pre-existing condition such as diabetes, lupus or HIV infection. It is estimated to affect up to 40,000 patients per annum in the U.S. alone.
The current treatment options include the use of Corticosteroids, Immunosuppressive drugs, Plasmapheresis, ACE Inibitors (angiotensin converting enzyme inhibitors) and ARB’s (angiotensin II receptor blockers). According to a report by Transparency Market Research, the global focal segmental glomerulosclerosis (FSGS) market that was valued at US$7.82 billion in 2016 is expected to reach US$15.83 billion by 2025, growing at a CAGR of 8.0%. The growing incidences of diabetes related complications and increased awareness will drive the growth in the market.
There is a concerted effort by non-government and public health organizations to encourage research and development of cure for this syndrome as evidenced by efforts by organizations such as NephCure Kidney International, The Kidney & Urology Foundation of America (KUFA), EURORDIS, and The National Organization for Rare Disorders (NORD).
We take a look at few clinical-stage biopharmaceutical companies that are working at improving the treatment options and outcomes in patients affected by this chronic disease.
Retrophin (NASDAQ: RTRX)
Market Cap: $755.44M; Current Share Price: 18.23 USD
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The company is developing sparsentan, a first-in-class drug that offers a dual mechanism of action by combining angiotensin receptor blockade with endothelin receptor blockade, which has a potent effect on proteinuria besides achieving renin-angiotensin inhibition in clinical studies. It is currently undergoing Phase III clinical trials and has the potential to be the first FDA-approved pharmacologic treatment for focal segmental glomerulosclerosis (FSGS), upon approval. It was granted an Orphan Drug Designation (ODD) by the FDA and EU in 2015.
It initiated crucial Phase 3 clinical trial of sparsentan in FSGS named DUPLEX, as a precursor to filing for an Investigational New Drug Application (NDA), based on an interim analysis of proteinuria as measured by changes from baseline in estimated glomerular filtration rate or, eGFR. In addition, the drug is also being evaluated for IgA nephropathy (IgAN), an immune complex mediated chronic glomerular disease, which results in excess proteinuria followed by renal failure. It is currently undergoing Phase III clinical trials named PROTECT to study its long-term neuroprotective abilities
Retrophin’s pipeline consists of fosmetpantotenate for the treatment of pantothenate kinase-associated neurodegeneration (PKAN) and CNSA-001 for the treatment of phenylketonuria (PKU), which is being developed in collaboration with Censa Pharmaceuticals, for the treatment of phenylketonuria (PKU).
As per its Q1, 2019 financial results, the company will make a decision about acquiring Censa Pharmaceuticals during the Q3, 2019, based on an evaluation of the complete Phase 2 proof-of-concept study results of CNSA-001 in patients with phenylketonuria (PKU). It had cash, cash equivalents and marketable securities worth $447.6 million as of March 31, 2019
ChemoCentryx (NASDAQ: CCXI)
Market Cap: $686.13M; Current Share Price: 11.82 USD
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ChemoCentryx is a clinical-stage biopharmaceutical company that focuses on creating innovative therapeutics for treatment of autoimmune, inflammatory and Oncology disorders with primary focus on orphan and rare diseases. Its approach is centered on developing discrete chemokine or chemoattractant receptors that block the negative inflammatory or suppressive response while leaving the rest of the immune system intact.
Its lead drug candidate for treatment of FSGS is CCX140, that targets the C-C chemokine receptor 2 (known as CCR2), which is responsible for kidney damage in patients suffering from FSGCS. Clinical studies have shown that CCR2 Inhibition improves cell health, reduces scarring and proteinuria. The company is currently enrolling patients in LUMINA-1, a study designed to access the safety and efficacy of CCX140, for treatment of those suffering from FSGS and LUMINA-2 for those diagnosed with FSGS with Nephrotic Syndrome.
It has an extensive pipeline covering areas such as ANCA- associated Vasculitis, C3 Glomerulopathy, Hidradenitis Suppurativa (Avacopan / CCX168)/ C5aR), CCX140/ for Diabetic Nephropathy, CCX507/ CCR9 ,CCX587/ CCR6 for autoimmune diseases such as ulcerative colitis and Th17 driven diseases and CCX872/ CCR2 ,CCR1, CXCR2 for immuno-Oncology indications such as pancreatic cancer and other targets.
The company has entered into a joint development agreement with Vifor Pharma (SWX: VIFN) to develop CCX140 for renal diseases. As part of the agreement it will retain the marketing rights for U.S. and China while Vifor will exercise rights over the rest of the markets worldwide.
As per its Q1, 2019 financial results, cash, cash equivalents and investments totaled $234.1 million as of March 31, 2019 including $73.3 million in net proceeds from the issuance of common stock.
Aurinia Pharmaceuticals (NASDAQ: AUPH)
Market Cap: $616.97M; Current Share Price: 6.66 USD
Data by YCharts
It is developing an investigational drug voclosporin to be used as a potential treatment for Focal Segmental Glomerulosclerosis (FSGS) In addition, the company is also looking at using voclosporin as a topical ophthalmic solution for the treatment of dry eye disease and Lupus Nephritis (LN). Voclosporin’s unique binding action induces structural changes in calcineurin and increases immunosuppressive activity. It is a best-in-class calcineurin inhibitors (CNI) with a dual mechanism of action that can not only block IL-2 expression and T-cell mediated immune responses but also stabilizes the podocyte in the kidney.
Volcosporin has shown to be more effective than conventional calcineurin inhibitors (CNI) by demonstrating a more stable pharmacokinetic and pharmacodynamic interplay and improved metabolic profiles. The company is engaged in Phase II clinical trials to assess voclosporin for the treatment focal segmental glomerularsclerosis, or FSGS and is currently enrolling patients for the same.
Voclosporin enjoys composition of matter patent protection until October 2027 in the U.S.
As of March 31, 2019, its cash, cash equivalents and short-term investments were at $144.3 million as compared to $125.9 million as on 31 December 2018. The company closed an At-the-Market (ATM) offering for the sale of 4,608,409 shares at $6.55 a share for gross proceeds of $30 million in November 2018.
Zyversa Therapeutics (Private)
Zyversa Therapeutics (Previously Variant Pharmaceuticals) is a clinical-Stage specialty biopharmaceutical company’s focus is on developing novel therapeutics for patients with inflammatory or renal diseases. Its lead candidate is VAR 200, a 2-hydroxypropyl-beta-cyclodextrin (2HPβCD) phase 2a-ready cholesterol efflux mediator that can eliminate cholesterol from podocytes, and is indicated for the treatment of focal segmental glomerulosclerosis (FSGS) and other orphan renal diseases. In addition, it is also developing a novel inflammasome inhibitor that can inhibit the ASC component of inflammasomes, block intracellular initiation of the inflammatory cascade and extracellular perpetuation of inflammation as a potential treatment for inflammatory diseases.
VAR 200, a 2-Hydroxypropyl-Beta Cyclodextrin (2HPβCD), is primarily an oligosaccharide of 7 glucose (sugar) molecules that has to be administered intravenously or subcutaneously, owing to a poor bioavailability that interacts with cell membranes to eliminate cholesterol out of cells protecting them against structural damage.
In clinical studies, it has demonstrated its ability to protect against cell damage in the kidneys, reduce proteinuria, cholesterol levels, fibrosis, improve metabolic control and renal function in patients suffering from FSGS, Alport Syndrome and Diabetic Nephropathy.
Its pipeline consists of drugs targeted at inflammatory disease such as Lupus Nephritis, Multiple Sclerosis and NASH, in addition to renal conditions like FSGS, Alpor Syndrome and Diabetic Kidney Disease.
ZyVersa’s Intellectual property rights portfolio has two notices of allowances from the USPTO for hydroxypropyl-β-cyclodextrin (HPβCD) for use in renal diseases (licensed from L&F Research LLC). Claim 14/967,831 relates to the use of HPβCD to treat FSGS and Alport Syndrome, reduce progression of FSGS, and reduce recurrence of FSGS following transplant, while claim 14/391,236 relates to the use of HPβCD or its derivatives to treat or reduce progression of Diabetic Kidney Disease.
Disclosure: I/we have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours.
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