The accumulated pre-clinical experience on the pharmacological effects of the EGF in terms of restoration and citoprotection, the technology expertise reached in the manufacturing of this molecule as a recombinant protein, its formulation as injectable, and the existence of a well-focus management orientation to research project development were the active ingredients to start the design of the product Heberprot-P® as a pharmaceutical composition to be applied through intralesional infiltration as a support treatment to accelerate healing of deep and complex ulcers derived from Diabetes mellitus, including neuropathic and neuroischemic ulcers with an ankle–brachial index pressure (ABI) between 0,3 and 0,8.
After demonstration that Heberprot-P® contributed to the restoration of the granulation tissue, which is the joint material of tissues in open traumas, the CIGB and the National Institute of Angiology and Vascular Surgery (INACV) used Heberprot-P® with successful results in a pilot clinical trial, from 2001 to 2002, in 29 type-II diabetic patients with micro and/or vascular macroangiopathy. Patients with neuropathic and ischemic infectious events, and ulcers with area higher than 20 cm2 (grade 3 and 4 according to Wagner’s classification) were included in the study. As a result of this first study, lower limbs of 58% of patients were saved and the recurrence rate was notably low (Berlanga J, Savigne W, Valdez C, Franco N, Alba JS, del Rio A, et al. Epidermal Growth Factor intra-lesional infiltrations can prevent amputation in diabetic patients with advanced foot ulcers. International Wound Journal. 2006, 3: 232-239).
A second phase I-II clinical trial in 41 patients finished in 2005 with even better efficacy results, measured by total wound healing in 50% of patients treated with Heberprot-P®, and preserving the limb in 66% of patients (Fernández-Montequín José F. et al., Intralesional Injections of Citoprot-P (recombinant Human Epidermal Growth Factor) in Advanced Diabetic Foot Ulcers with Risk of Amputation. International Wound Journal. 2007, 4: 326-327). Heberprot-P® has successfully applied in more than 1000 Cuban patients with DFU, and a heavy burden of work is currently been performed to accelerate its application in with the support of the National Direction of Primary Health Attention. The use of Heberprot-P® and the integral management of DFU in every diabetic attention services (498 Cuban hospitals) is been implemented by the National Direction of Post-grade and the National Group of Active Screening from the National Ministry of Health (MINSAP).
The product has been approved for commercialization in Cuba, Venezuela and Argentine. A randomized, double-blinded phase III clinical trial controlled with placebo was done in 149 Cuban patients with positive safety and efficacy results. The therapy with Heberprot-P® fill the huge gap of an urgent unmet medical need for the treatment of complex DFU, from 1 to 420 cm2 in neuropathic and neuroischemic patients.