Scar tissue is an integral part of the healing process following any surgery. In total knee replacement (TKR) surgery, excess scarring or arthrofibrosis can cause joint pain and severely limit the range of motion of the joint. As many as one million TKR procedures may be performed in the U.S. during 2015. Approximately eight percent of these will require follow-up revision surgery to restore acceptable range of motion to the joint and reduce pain. Projected direct costs to the U.S. health care system will be $2.3 billion, while significant delays in patient recovery add substantial additional economic costs to patients and businesses.
Market Impact: Total U.S. sales of BTL-slo for arthrofibrosis following TKR surgery are projected to be $640 million. EU sales are expected to be approximately half of U.S. sales, or $320 million. With related uses, total sales of $1.2 billion are projected for its peak year.
Safety: Toxicology of BTL-slo has been evaluated in several studies in dogs and rats. No organ or tissue damage has been noted in any of these studies. Dose levels of up to 5,000X the anticipated human dose have been administered daily by tail vein injection in rats for seven days without adverse effects.
Efficacy: The anti-scarring properties of BTL-slo are evident from genomic, cellular, tissue, pre-clinical animal studies.
Mechanism of Action: BTL-slo was evaluated for its effects on wound healing in human skin ex-plant cultures, where it was shown to stimulate both migration and proliferation of keratinocytes in a scratch assay model, and to modulate CD-44, the hyaluronan receptor. Analysis of gene activation in various cell types showed a consistent modulation of regulatory genes by BTL-slo. BTL-slo reduced fibrosis in two murine models of excess collagen: 1) a genetically induced model of scleroderma (tsk mouse strains), and 2) a bleomycin-induced skin fibrosis model.
Intellectual Property: Patents are prosecuted in the U.S. and most other major health care markets throughout the world. Patents pertaining to tendonitis and connective tissue disorders have projected lives through 2027 and 2023, respectively. Being a biological, BTL-slo is anticipated to qualify for 12 years of market exclusivity in the U.S. following approval of its Biologics License Application (BLA) under provisions of the Patient Protection and Affordable Care Act. In the EU, agents are anticipated to have 10 years of market exclusivity following approval from the EMEA.
Currently, a Phase 1b/2a clinical study is targeted for initiation in 2015 in patients suffering from complications resulting from total knee replacement surgery.