PDGF product receives Canadian approval
April 1, 1999
PDGF product receives Canadian approval
Clinical trials continue for additional uses
As reported in the March 1998 issue of Wound Care, the genetically engineered platelet-derived growth factor (PDGF) becaplermin gel 0.01%, marketed as Regranex, received approval from the Food and Drug Administration in late 1997. The indication approved was treatment of lower-extremity neuropathic diabetic ulcers that extend into the subcutaneous tissue or beyond and have an adequate blood supply.
In February, Regranex also received approval from Health Canada’s Therapeutic Products Programme, again for the treatment of diabetic foot ulcers, which are the leading cause of amputation among Canadians with diabetes. Diabetic foot ulcers precede about 85% of all amputations in patients with diabetes, and account for more hospital days than all other diabetic complications combined. In Canada, the estimated direct and indirect costs of an amputation are between $35,000 and $50,000. Additionally, $5 billion to $6 billion is spent annually in Canada for the treatment of diabetes and its complications.
Diabetics often are insufficiently aware of foot ulcers because nerve damage and visual and circulatory problems make feeling or seeing ulcer development difficult. Several population-based studies have reported the prevalence of diabetic foot ulcers and help to illustrate the worldwide extent of the problem. Investigators in Stockholm have found the prevalence of diabetic foot ulcers to be 4.4% in Sweden.3 British studies have shown the prevalence of diabetic foot ulcers to range from 5.3% to 7.4%.4 Moreover, a study conducted in Sweden that investigated the long-term prognosis for diabetic patients with foot ulcers revealed high recurrence rates for ulcers (up to 70%) and high rates of amputations (12% to 48%) over five years of follow-up.5 Amputation is associated with a higher risk of subsequent amputation and a decreased survival rate to approximately 50% for the first three years after limb loss.4,5,6
PDGF plays an important role in initiating and regulating the wound healing process. Activated platelets are the first cell types to invade the wound site and start the healing process by releasing several growth factors, including PDGF, which plays an important role in all phases of the wound healing process. PDGF stimulates the proliferation of cells involved in the inflammatory response and the proliferation and migration of fibroblasts and smooth muscle cells. All of the principal cell types that migrate into the wound site either synthesize and release PDGF or are responsive to it. PDGF also stimulates both the synthesis of extracellular matrix components and the lysis of collagen by collagenases. Because human skin fibroblasts are more responsive to the B chain of PDGF, the BB homodimer of PDGF is used exclusively in the formulation of becaplermin gel.2
The effects of becaplermin gel have been assessed in four major clinical trials of nearly 1,000 patients with full-thickness lower-extremity diabetic ulcers.7,9 In these trials, the diabetic ulcers were of at least eight weeks duration and had an adequate blood supply. Median ulcer size at baseline ranged from 1.4 cm2 to 3.5 cm2. All patients received a program of good wound care, consisting of initial debridement, a nonweight-bearing regimen, systemic treatment for infection if present, moist saline dressings, and additional debridement as necessary. Becaplermin gel or placebo gel was applied once daily for 20 weeks or until complete healing was achieved. Results of these trials showed that becaplermin gel increases the incidence of healing and decreases the time to healing in patients with lower-extremity neuropathic diabetic ulcers8,9 when used in conjunction with good ulcer care practices, including pressure relief, infection control, and initial debridement of the wound.
Results of the phase III trial demonstrated that during up to 20 weeks of treatment, 50% of wounds were completely healed in patients receiving becaplermin gel compared with 35% of wounds in patients receiving placebo gel.7,9 Furthermore, daily treatment with becaplermin gel decreased healing time by 32%, or approximately six weeks, compared with placebo gel. Becaplermin gel was well-tolerated in all clinical trials.
The manufacturer estimates that the average amount of Regranex needed for foot ulcer therapy is one and a half to two tubes of the product, which is applied directly to the ulcer once a day. Wholesale price for the product in the United States is $350 per tube.
[Editor’s note: For more information, call Regranex at (888) 734-7263.]
References
1. Study shows faster healing with use of new growth factor. Wound Care 1998; 4:35.
2. News from industry. European Tissue Repair Society bulletin. Web site: http://www.leahcim.demon.co.uk/etrs.htm.
3. Rosenqvist U. An epidemiological survey of diabetic foot problems in the Stockholm County 1982. Acta Med Scand 1984; 687 (suppl): 55-60.
4. Reiber GE. The epidemiology of diabetic foot problems. Diabet Med 1996; 13:S6-S11.
5. Apelqvist J, Larsson J, Agardh CD. Long-term prognosis for diabetic patients with foot ulcers. J Intern Med 1993; 233: 485-491.
6. Bodily KC, Burgess EM. Contralateral limb and patient survival after leg amputation. Am J Surg 1983; 146: 280-282.
7. Steed DL, the Diabetic Ulcer Study Group. Clinical evaluation of recombinant human platelet-derived growth factor for the treatment of lower extremity diabetic ulcers. J Vasc Surg 1995; 21:71-81.
8. Wieman TJ, Smiell JM, Su Y. Efficacy and safety of a topical gel formulation of recombinant human platelet-derived growth factor-BB (Becaplermin) in patients with chronic neuropathic diabetic ulcers: a phase III, randomized, placebo-controlled, double-blind study. Diabetes Care 1998; 21:822-827.
9. d’Hemecourt PA, Smiell JM, Karim MR. Sodium carboxymethylcellulose aqueous-based gel vs. becaplermin gel in patients with nonhealing lower extremity diabetic ulcers. Wounds 1998; 10:69-75.
You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content