Calciphylaxis: Rare Yet Potentially Fatal

Did you know that Calciphylaxis, or calcific uremic arteriolopathy (CUA), although affects merely 1 to 4 % of patients undergoing dialysis, has a dismal prognosis with up to 80% mortality? In addition to numerous comorbidities which affect the majority of dialysis patients, Calciphylaxis is a painful and often fatal condition, for which no commonly accepted disease-modifying treatment exists. Calciphylaxis is a rare condition involving subcutaneous vascular calcification and cutaneous necrosis, which is most often diagnosed in patients with renal failure. According to the literature survey, the condition is also defined as a metastatic calcinosis cutis and necrotizing or calcifying panniculitis. Various studies suggest that there can be significant morbidity and mortality from the disease, frequently resulting from septicemia due to the impaired integrity of the epidermis and dermis. A two-fold increase in mortality is seen when cutaneous ulcers develop.

Calciphylaxis can be classified as uremic (in patients with ESRD) or non-uremic (in patients with normal renal function or earlier stages of chronic kidney disease). According to KOL views, more than 80% of the diagnosed population for Calciphylaxis, fit to the category of those who had undergone dialysis and kidney transplantation, and hence occupy the characteristics and symptoms of uremic Calciphylaxis. On the contrary, the remaining proportion of the patient population belongs to non-uremic Calciphylaxis population, wherein the risk factors include primary hyperparathyroidism, malignancy, alcoholic liver disease, connective tissue diseases, diabetes, Crohn’s disease and others.

Due to the lack of approved therapeutic regimens for calciphylaxis, management involves a multi-disciplinary approach consisting of primary prevention, wound care and infection prophylaxis, controlling disease progression, and treatment of the systemic disease. While a standard treatment protocol has not yet been developed for Calciphylaxis, however, according to a literature survey various therapeutic options have shown good efficacy in treating Calciphylaxis. Highlighting disease prevention, i.e., by early identifying and treating renal disease with specific attention to calcium-phosphate homeostasis, is of the utmost importance. Generally, the treatment of calciphylaxis is a multimodal and interdisciplinary approach. The current therapeutic landscape of Calciphylaxis can be broadly divided into two categories: Conventional Treatment and Combination Treatment (multi-target). Conventional treatment options, which are generally prescribed to nearly one-fourth of the patient population,
can be further categorized as Intensification of Hemodialysis and Amputation. Dialysis prescription is optimized to achieve the recommended Kidney Disease Outcomes Quality Initiative (K/DOQI) goals of dialysis adequacy. The cases where all other supportive and conservative measures have failed, revascularization and amputation may be the only treatment option.

On the contrary, the combination treatment involves intensified hemodialysis and preference of products with a lower calcium content. Traditional therapeutic approaches which have proven to be effective in various cases for the treatment if Calciphylaxis, include Sodium thiosulfate, Bisphosphonates, Cinacalcet, Non-calcium chelators, and Vitamin K. Of all the above-mentioned treatment options, there are increasing reports of Sodium thiosulfate being used off-label to successfully treat both uremic and nonuremic Calciphylaxis. Other treatment options that are generally prescribed for the treatment of Calciphylaxis include pentoxifylline, paricalcitol, anticoagulants, narcotic analgesics etc. However, limited evidence is available regarding the efficacy of these drugs in the treatment of alciphylaxis. Based on the good safety and efficacy observed for the off-label drugs in the treatment of Calciphylaxis, DelveInsight expects that the market size of the currently available off-label therapies for the treatment of Calciphylaxis will experience stable growth in the coming years. However, the emerging therapies targeted to reduce the symptoms of Calciphylaxis, are expected to fuel the growth of the market.

The overall dynamics of Calciphylaxis market is anticipated to change in the coming years in regard to the expected launch of potential therapies, i.e. Sodium thiosulfate (Hope Pharmaceuticals) and SNF472 (Sanifit), during the forecast period [2018-2027]. Sodium thiosulfate, currently in Phase III of clinical development and has received orphan designation by the European Commission and US FDA, is expected to grab maximum market share, owing
to the already proven greater safety and efficacy of the drug, which has been proven in various trials. A systematic review showed that approximately 70% of patients reported improvement in skin lesions or pain relief and did not die.

Overall, the increasing incidence, awareness of the disease and promising emerging pipeline therapies will propel the market size forward during the forecasted period of 2018-2027. The expected launch of emerging therapies may increase the market size in the coming years, aided by an increase in the population undergoing dialysis, kidney transplant and an incident population of Calciphylaxis.