Wound healing is a complex biological process. In order for a wound to heal normally, components need to be controlled, synchronized and balanced. If this interaction is disturbed, the result will be an excessive repair process (for example, tissue hypertrophy or adhesion) or a wound that does not heal. The wounds are usually treated differently depending on whether it is an acute wound (i.e. after accident or surgery) or hard-to-heal or chronic wounds.
Chronic wounds are predominantly venous leg ulcers (caused by poor vascular function in the legs), diabetic ulcers (caused by neuropathy and peripheral vascular disease) and pressure ulcers. A common definition of a chronic wound is a wound that has not shown a tendency to heal within six weeks (1).
Irrespective of wound, the healing time is affected by, among other things, the age of the patient, general condition, nutritional status, smoking, mobility and chronic diseases such as diabetes. The aim of treating wounds is to accelerate healing and prevent infections, but also to reduce pain, bad odor and adhesions as well as other complications.
The product candidates of Promore Pharma are part of the bioactive wound care segment within the larger wound care market. Bioactive wound care products typically contain sophisticated polymers (such as collagen, alginate and silicon) and in certain cases pharmaceutical agents. The global market for wound care products is projected to grow from 17 billion USD in 2016 to over 20 billion USD in 2021, which corresponds to a compound annual growth rate of 3.6 percent (2). Within the global wound care market Promore Pharma’s product candidates are intended for the bioactive wound care segment, which constitutes the fastest growing segment within the overall wound care market with a projected annual growth rate from 2015-2020 of 14 percent (3).
An increase in chronic diseases, such as diabetes, peripheral artery disease, cardiovascular disease as well as immune disorders and other conditions that deteriorates the natural healing process is expected to result in an increased demand for bioactive wound care products; e.g. treatments for diabetic foot ulcers and venous leg ulcers. Moreover, an increase in consumer awareness associated with expectation on bioactive wound care treatments, instead of traditional wound care products in combination with an ageing population and increasing wound related complications, are factors what will drive market growth in the future. In the US, the market is also driven by more favorable reimbursement from health authorities and private insurance schemes for curative therapies (4).
The drug candidate PXL01 is currently being developed for preventing adhesions after flexor tendon surgery. The Company estimates that there are a large number of potential medical applications for PXL01, for instance within the areas of preventing adhesions after spinal surgery and prevention of dermal scarring from surgical wounds or traumatic injury.
The drug candidate LL-37 is currently being developed for the treatment of venous leg ulcers (VLU) and the Company also sees a potential indication broadening opportunity in diabetes foot ulcers (DFU).
Post-surgical adhesions and dermal scarring (PXL01)
Post-surgical adhesions are permanent adhering of tissue surfaces that should be separated under normal conditions. Adhesions represent one of the most common and most costly post-surgical complications; it has been estimated that the annual costs are 1-2 billion USD in the US alone (5). Adhesions can cause pain, infertility, reduced function/mobility, requirement for secondary surgical procedures and difficulties to undergo future surgical procedures.
All current treatments for post-surgical adhesions are registered as medical device products and are based on the concept of physical separation of the adhering tissue surfaces.
The Company foresees that PXL01 has the potential to become the first pharmaceutical product to prevent adhesions and is anticipated to provide a better efficacy and safety as compared with competing products.
Flexor tendon injuries are caused by professional as well as recreational activities, e.g. sports. A common cause for a flexor tendon transection are injuries involving sharp tools, for instance a cut-injury when an avocado is de-pitted with a kitchen knife. It is estimated that approximately 1 in 1,000 (general population) are afflicted with tendon injuries per year, corresponding to 300,000 injuries in US alone, where injuries in the hand account for approximately one third (6). The Company has assumed that the incidence is similar among Western countries since workers’ protection guidelines and recreational activities are comparable.
Flexor tendon repair surgery is a procedure involving several small lacerations of the skin covering the damaged tendon, suturation of the tendon with special filaments and subsequent closure of the wound. The procedure is followed by intensive rehabilitation for up to 12 weeks to reduce the risk for adhesions and increase the mobility.
A small restriction in mobility can have a large impact on the patient’s quality of life. If the mobility is reduced by only 10 degrees, the patient loose fine motorics and can experience difficulties in common activities such as closing a button, eating with chopsticks or handling small objects. In cases where the mobility is severely reduced it may compromise professional capabilities. Moreover, trauma in the hand can be accompanied by nerve damage that often result in sensory loss. In some cases, the patient may experience pain, stiffness and reduced strength. According to estimates of the Company, between 20 and 50 percent of all patients undergoing flexor tendon repair surgery in the hand experience reduced mobility.
Degenerative disc disorder (“DDD”) is one of the most common causes of lower back and neck pain and affects approximately 30 million people worldwide every year. The global market for spinal fusion and spinal disc surgery, excluding minimally invasive spine devices, currently exceeds 7 billion USD, according to GlobalData. Treatments such as physical therapy or anti-inflammatory medications may provide adequate relief of troubling symptoms. However, surgery is often recommended if the conservative treatment options do not provide relief within two to three months. Postoperative epidural fibrosis (scar) represents a common reason for failure of surgical interventions in DDD. The concomitant use of an anti-scarring agent at the time of surgery may therefore increase the likelihood of a successful procedural outcome.
Cutaneous scars commonly form after surgical procedures, such as plastic surgery or caesarean sections, trauma, burns and infections. It is estimated that more than 100 million people develop scars after trauma and elective surgery in the traditional pharmaceuticals markets every year.
Furthermore, a notable proportion of this population will require surgical intervention for their scars due to aesthetic considerations or functional impairment. Consumer surveys also show that a very high share of plastic surgery patients is willing to pay to reduce or prevent scarring. The global scar treatment market is expected to approach a value of 35 billion USD by 2025, according to several independent estimations. Today, there are no pharmaceutical prescription products available for preventing scar formation.
Chronic Wounds (LL-37)
Chronic ulcers are generally defined as wounds that do not show signs of healing within six weeks, despite regular cleaning and wound care. Chronic ulcers are generally dived into three main categories; venous leg ulcers, diabetic foot ulcers and pressure ulcers. Chronic wounds can effuse wound fluid, bleed, cause pain and bad odor, and can reduce the mobility of the patient. Open wounds are often colonized with bacteria and fungi that can cause wound infections. In severe cases, the wounds can result in hospitalization and amputation of an extremity. The regular management of a wound, typically involve care visits 2-3 times per week and also result in reduced professional capability for the patient and significant healthcare costs for the society. In the US alone, it is estimated that the aggregated healthcare costs for patients with hard-to-heal ulcers exceed 25 billion USD annually (7).
Venous Leg Ulcers (LL-37)
Venous leg ulcers are the largest category of chronic wounds comprising approximately 40 percent of all hard-to-heal ulcers (8). The most common cause for venous leg ulcers is insufficient blood circulation in the lower legs and this condition is not screened for and therefore typically is discovered late in the health care system. Inadequate blood flow in the legs may result in swelling due to edema and the skin becomes more sensitive to damage; because of the vascular dysfunction, leg wounds heal slower. The risk to acquire non-healing venous leg ulcers increase with age and obesity (9).
Diabetic Foot Ulcers (LL-37)
There are an estimated 425 million people in the world with diabetes, and this number is forecasted to increase to 629 million by 2045 (10). In the US, an estimated 900,000 people develop diabetic foot ulcers annually, in a diabetic population of approximately 21 million.
(1) Definition according to Swedish Medical Products Agency
(2) Markets and Markets “Wound care market – Global forecast to 2021”
(3) Technavio ”Global bioactive wound care market 2016-2020”
(4) Global Bioactive Wound Care Market 2016 – 2020
(5) Fox Ray NF, Larsen JW, Stillman RJ, Jacobs RJ. Economic impact of hospitalizations for lower abdominal adhesiolysis in the United States in 1988. Surg Gynecol Obstet 1993;176
(6) De Jong et al, The Incidence of Acute Traumatic Tendon Injuries in the Hand and Wrist: A 10-Year Population-based Study. Clin Orthop Surg. 2014 Jun; 6(2): 196–202.
(7) Sen, CK, et al, Human Skin Wounds: A Major and Snowballing Threat to Public Health and the Economy. Wound Repair Regen. 2009 Nov–Dec; 17(6): 763–771.
(8) : J. Bradford Rice, Urvi Desai, Alice Kate G. Cummings, Howard G. Birnbaum, Michelle Skornicki & Nathan Parsons, Burden of venous leg ulcers in the United States, Journal of Medical Economics, 2014 17:5, 347-356
(9) Vivas A. et el. Venous Leg Ulcers. J Ann Intern Med. 2016;165(3).
(10) International Diabetes Federation (Diabetes: Facts and figures 2017)