Diseases

Orphan and Rare Diseases 2018-04-13T17:51:48+00:00

Orphan and Rare Diseases

ANCA Associated Vasculitis (AAV)

ANCA Associated Vasculitis (AAV) is a rare, severe, and often fatal autoimmune disease that is caused by autoantibodies called anti-neutrophil cytoplasmic antibodies and is characterized by inflammation that can affect many different organ systems, and commonly involves the kidneys. AAV affects approximately 40,000 people in the US (with approximately 4000 new cases each year) and greater than 75,000 people in Europe, with at least 7500 new cases each year, and is currently treated with courses of immuno-suppressants (cyclophosphamide or rituximab) combined with high dose steroid administration. Following initial treatment, up to 30 percent of patients relapse within 6 to 18 months, and approximately 50 percent of all patients will relapse within 3 to 5 years.

The current standard of care for AAV is associated with significant safety issues. First year mortality is approximately 11 to 18 percent. The single major cause of premature mortality is not disease related adverse events, but rather infection that is thought largely to be a consequence of steroid administration. The multiple adverse effects of courses of steroid treatment (both initial courses and those that are repeated as a consequence of relapse) are major causes of both short-term and long-term disease and death. Such therapy-related adverse events contribute significantly to patient care costs, as well as to the diminution of quality of life for patients.

C3 Glomerulopathy (C3G)

C3G disease is an ultra-rare disease of the kidney that is characterized by deposition of the protein known as C3 in the glomeruli, or filtration units of the kidney, thus causing renal damage. While the disease name refers to complement 3, it is well known that the C5a receptor pathway, which is further downstream of C3 in the complement cascade and the target of avacopan, is an essential part of the disease causing pathology. Hence, C3 is a marker of the downstream effects of C5aR.

Hidradenitis suppurativa (HS)

Hidradenitis suppurativa (HS) is a chronic, inflammatory, debilitating skin disease characterized by recurrent, painful, nodules and abscesses, ultimately leading to the formation of draining fistulas (also known as sinus tracts) as well as scarring. The diseases originates from inflammation and occlusion of the hair follicle. Apart from pain, the nodules may rupture, and often extrude a purulent, foul-smelling discharge leading to substantial social embarrassment for these patients. Due to its chronic nature and frequently occurring relapses of the skin lesions, HS has a great impact on the patient’s quality of life, deeply affecting social, working, and psychological aspects.

In the United States, moderate to severe HS has orphan designation with an estimated prevalence of up to 200,000 patients. In Europe, the number of affected patients is believed to be greater, with higher prevalence.

Depending on the severity of disease, the current standard of care for HS patients includes topical, oral or intravenous antibiotic treatment, as well as surgery.

Adalimumab, an anti-TNF-alpha monoclonal antibody, is the only drug indicated for the treatment of patients with moderate to severe HS. Two pivotal adalimumab trials showed that approximately 50% of the patients who were treated with adalimumab achieved an improvement in their skin lesion, as measured by the widely accepted HiSCR (Hidradenitis Suppurativa Clinical Response) assessment instrument. There remains a high unmet medical need, however, as a very large proportion of the patients with moderate to severe HS do not adequately respond to adalimumab or other therapies used in the standard of care.

Atypical Hemolytic Uremic Syndrome (aHUS)

Atypical Hemolytic Uremic Syndrome (aHUS) is a genetic, chronic, rare disease that is caused by the formation of blood clots within blood vessels, or thrombosis, throughout the body. aHUS affects both adults and children and can progressively damage vital organs, including the kidneys, but also other organs such as the brain, heart, lungs, gastrointestinal tract, and pancreas.  These clots can cause serious medical problems if they restrict or block blood flow.

As a result of clot formation in small blood vessels, people with aHUS experience kidney damage and acute kidney failure that lead to end-stage renal disease (ESRD) in about half of all cases. These life-threatening complications prevent the kidneys from filtering fluids and waste products from the body effectively.

Current aHUS treatment is either ineffectual or too expensive, and as a result, out of reach for many aHUS patients.

Focal Segmental Glomerulosclerosis (FSGS)

FSGS is a rare form of chronic disease kidney that affects approximately 80,000 patients in the U.S. and Europe, with 5,500-9,500 new cases each year. FSGS attacks the kidney’s filtering units (glomeruli) causing serious scarring which leads to permanent kidney damage. Progressive FSGS can lead to end-stage renal disease, ultimately requiring kidney transplant or renal dialysis and total health expenditures of hundreds of thousands of dollars each year per patient. Currently there are no FDA approved treatments for FSGS, but typically steroids are used to try and control proteinuria.

Each kidney is made up of approximately one million tiny filters called “glomeruli”. Glomeruli filter blood, taking out the water-like part that becomes urine and leaving the protein in the blood. When glomeruli, or sections of the glomeruli become damaged or scarred (sclerosis), proteins leak into the urine (proteinuria).

While symptoms of FSGS may not be noticeable, when they are present they may include: proteinuria, edema, low blood albumin levels, high cholesterol and/or high blood pressure in some cases.