Critical limb ischemia (CLI) is a severe peripheral arterial disease (PAD) characterised by blockage in the arteries of the lower limbs, which in turn reduces blood-flow. The primary cause of the disease is atherosclerosis or the buildup of fatty deposits called plaque in the arteries. Other risk factors for the disease include hypercholesterolemia, obesity, smoking, hypertension and diabetes. Diabetes is a significant risk factor because it is often linked with severe PADs. The most common symptoms of CLI are the ischemic rest pain — extreme pain or hard to heal sores on the feet or legs. CLI is associated with high risk for cardiovascular events, including myocardial infarction and in some cases death due to CLI. Auscultation, ankle-brachial index (ABI), magnetic resonance angiography (MR angiography), doppler ultrasound, CT angiography and angiogram are some of the tools to diagnose CLI. Treatment of the disease include medications for pain relief, endovascular treatments such as angioplasty, stents, laser atherectomy, directional atherectomy and surgical treatments such as amputation of the limb.
Considerable growth is expected in the therapeutics pipeline for CLI in the near future mainly due to rising old-age population, increasing incidence of CLI and its risk factors such as diabetes and obesity. Increasing investment by companies for the research and development of drug candidates for the treatment of CLI is also a major factor driving the growth of pipeline of CLI therapeutics, globally. Lack of an approved treatment for the disease is one of the key factors encouraging companies to invest in the research and development of therapeutics for the treatment of CLI.
In January 2016, Caladrius Biosciences, Inc. initiated a Phase II clinical study to assess the efficacy and safety of CLBS12 in patients with CLI due to arteriosclerosis obliterans with a single-arm substudy to assess the safety and potential efficacy of CLBS12 in patients with CLI due to buerger's disease. The study is expected to be completed in July 2020. Caladrius Biosciences, Inc. recently completed consultations regarding a Phase 2 CLBS12 protocol with the regulatory authorities of Japan. In November 2016, Boston Scientific Corporation commenced a Phase II/III study to evaluate efficacy and safety of ranger drug-eluting balloon for below the knee angioplasty in patients with CLI. The study is expected to be completed in November 2018. Hemostemix Inc. is currently running a Phase II clinical trial of its drug candidate, ACP-01, in patients with CLI at clinical trial sites in the Canada and South Africa. ACP-01 is an autologous cell therapy to treat CLI in patients who are facing amputation. Angiogenic cell precursors (ACPs), secrete growth factors and cytokines which support the construction of blood vessels through vasculogenesis and angiogenesis.
Recently, Rexgenero Limited received confirmation from the European Medicines Agency (EMA) to accept the design of two confirmatory Phase III clinical trials for its drug candidate, Rexmyelocel-T, in patients with CLI. Additionally, Rejuveinix by Reven Pharmaceuticals, Inc. is also in Phase I/II stage of development for the treatment of CLI.
Some of the major players involved in the development of drugs for CLI include Caladrius Biosciences, Inc., Boston Scientific Corporation, Rexgenero Limited, Reven Pharmaceuticals, Inc., Mitsubishi Tanabe Pharma Corporation, Anesiva, Inc., Taiwan Bio Therapeutics Co., Ltd., Beike Biotech India Pvt. Ltd., Pharmicell Co., Ltd., United Therapeutics Corporation, Stempeutics Research Pvt. Ltd.