No-Option Refractory Disabling Angina (NORDA) – LSTA14 (OLOGO™ in the U.S.)
What is No-Option Refractory Disabling Angina (NORDA)?
No-option refractory disabling angina (NORDA) describes patients who have severe and disabling angina, which persists despite revascularization (e.g., bypass surgery or stenting) and optimal medical therapy.
Refractory angina (RA) is defined as three or more months of angina due to demonstrated coronary insufficiency that persists despite optimal medical therapy (1). No-option refractory angina (NORA) describes patients no longer amenable to further revascularization by either percutaneous or surgical revascularization (2). These patients typically have had repeated prior angioplasty and stenting or open-heart bypass surgery, or they can have unsuitable coronary anatomy with severe diffuse atherosclerosis or have other advanced comorbidities. A smaller sub-population of NORA patients have Canadian Cardiovascular Society (CCS) functional Class 3 or 4 angina resulting in severe limitation in their ability to perform activities of daily living. An even smaller sub-population of the no-option, CCS Class 3/4 population are those who meet the Institute of Medicine definition of cardiovascular disability by being able to exercise less than five metabolic equivalents (METS). This smaller subset of NORA patients has severely symptomatic, or disabling angina, and are described as NORDA (3).
Conventional Treatment Methods for Refractory Angina Patients
Patients with no-option refractory disabling angina (NORDA) have very severe symptoms and a poor prognosis. They have significant coronary artery disease that is not amenable to revascularization, and often have comorbidities that make them poor candidates for surgical (i.e., bypass grafting) or percutaneous coronary interventions. There is no cure for NORDA, and the condition is typically progressive. The goal of treatment is to relieve symptoms and improve quality of life.
NORDA patients have angina symptoms resistant to escalating pharmacological treatment and have suboptimal responses to traditional anti-ischemic drugs (i.e., beta blockers, calcium channel blockers, nitrates) used commonly for typical patients with angina.
Several treatments have been and are being developed to address NORDA including:
· Viral-based angiogenesis
· CD34+ cell therapy to induce neovascularization
· Coronary sinus reducer device
· Enhanced external counterpulsation
· Extracorporeal shockwave myocardial revascularization to stimulate neo-capilarization
· Transmyocardial laser revascularization
· Transcutaneous electrical nerve stimulation
· Neuromodulation to interrupt pain signals of angina (i.e., cardiac sympathectomy)
Our Approach: LSTA14 (OLOGO™ in the U.S.) for the treatment of no-option refractory disabling angina
The Company acquired the rights to the data and regulatory filings for this CD34+ cell therapy program in NORDA that had been advanced to Phase 3 by a previous sponsor. Based on the clinical evidence from the completed studies, a single administration of LSTA14, formerly known as CLBS14, (OLOGO™ in the U.S.) reduces mortality, improves angina, and increases exercise capacity in patients with otherwise untreatable angina. This product received a Regenerative Medicine Advanced Therapy (RMAT) designation from the FDA. The RMAT designation affords the product a more rapid 6-month review time for a biologics license application, once submitted. OLOGO™ will only continue in further development if a partner provides most, if not all, of the necessary capital.
Market Opportunity for NORDA
In the United States, we have identified fewer than 100,000 patients with NORDA as candidates for OLOGO™ (LSTA14), making this an orphan-size indication (3).
GBD 2015 Mortality and Causes of Death Collaborators. Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: a systematic analysis for the global burden of disease study 2015. Lancet. 2016;388:1459–544. doi:10.1016/S0140-6736(16)31012-1
McGillion M, Arthur HM, Cook A, Carroll SL, Victor JC, L’allier PL, Jolicoeur EM, Svorkdal N, Niznick J, Teoh K, et al; Canadian Cardiovascular Society; Canadian Pain Society. Management of patients with refractory angina: Canadian Cardiovascular Society/Canadian Pain Society joint guidelines. Can J Cardiol. 2012;28(2 suppl):S20–S41. doi: 10.1016/j.cjca.2011.07.007
Mannheimer C, Camici P, Chester MR, Collins A, DeJongste M, Eliasson T, Follath F, Hellemans I, Herlitz J, Lüscher T, et al. The problem of chronic refractory angina; report from the ESC joint study group on the treatment of refractory angina. Eur Heart J. 2002;23:355–370. doi:10.1053/euhj.2001.2706