ThromboGenics NV, a biotechnology company developing novel medicines for diabetic eye disease, has successfully enrolled the first patient in a phase 2 active-controlled, masked, multicenter study to evaluate the efficacy and safety of THR-317 administered in combination with ranibizumab (Lucentis, Novartis), for the treatment of DME (NCT03499223).

THR-317 (anti-PIGF) is a recombinant humanized monoclonal antibody directed against the receptor-binding site of human placental growth factor (PlGF) administered by intravitreal (IVT) injection. In pre-clinical models, anti-PlGF has been shown, in addition to anti-angiogenic properties to also be anti-inflammatory.  

Ranibizumab is a monoclonal antibody fragment against vascular endothelial growth factor (VEGF), anti-VEGF being the current standard of care for the treatment of DME. Ranibizumab is administered intravitreally.  

This phase 2 clinical study (THR-317-002) is designed to evaluate the safety and efficacy of IVT THR-317 along with ranibizumab, compared with ranibizumab monotherapy in patients with DME.

Patients will be randomized into either a combination arm of THR-317 (8mg) + ranibizumab, or ranibizumab plus a sham administration. The primary outcome measure is change from baseline in Best Corrected Visual Acuity (BCVA) at Month 3.

Simultaneous inhibition of VEGF (ranibizumab) and PlGF (THR-317) may have a better efficacy than either treatment alone. Non-clinical experiments indicate that anti-PlGF in the presence of an anti-VEGF antibody has an additive effect inhibiting the growth of new blood vessels (Van de Veire et al., 2010), a disease hallmark of DME. This may mean that a combination approach could result in a better treatment response.  The anti-PlGF component could bring the advantage of reduced inflammation associated with a reduced level of PIGF (van Bergen et al., 2017).   

Approximately 70 patients will be enrolled, of which about half will be anti-VEGF treatment naïve and the other half will have had a sub-optimal response to prior treatment with ranibizumab.

Initial results from the THR-317-002 study are anticipated in Q3 2019.

Susan Schneider, MD, chief medical officer of ThromboGenics, said: "Initiating this clinical study is an important milestone in progressing the development of this novel compound for the potential treatment of patients with DME. A combination approach to treating this multifactorial disease may provide better therapeutic outcomes than current standard of care for the treatment of diabetic eye disease."

Patrik De Haes, MD, chief executive officer of ThromboGenics, commented: "We are pleased to be moving THR-317 through clinical development as we continue to execute the strategic development of our novel diabetic eye disease pipeline. We look forward to bringing two additional candidates, THR-149 for the treatment of DME and THR-687 for the treatment of DR and/or DME, into the clinic this year."