TOKYO & PRINCETON, N.J.--(BUSINESS WIRE)--Otsuka Pharmaceutical Co., Ltd., and its indirect subsidiary Otsuka Pharmaceutical Development & Commercialization, Inc. (Otsuka), announce that the latter has been awarded a grant for up to US $10 million from the Bill & Melinda Gates Foundation to advance clinical development of Otsuka’s investigational compound to treat tuberculosis (TB), OPC-167832, in combination with delamanid as the backbone of a pan-TB regimen in line with the World Health Organization’s (WHO) Target Regimen Profiles (TRP).
The WHO TRPs are meant to assist drug developers in identifying important drug regimen features and aligning these with patient and programmatic needs at a country level. A pan-TB regimen could revolutionize TB treatment by offering an effective, 3-or-4 drug, fully oral regimen with an acceptable safety profile that could be administered to almost all patients with active TB regardless of their drug resistance profile.1
In 2017, Otsuka completed a phase 1, single-ascending-dose study of OPC-167832. OPC-167832 is also being evaluated in pre-clinical studies using the hollow fiber system at the Baylor Scott & White Research Institute and in additional non-clinical studies in collaboration with the U.S. National Institutes of Health / National Institute of Allergy and Infectious Diseases.
The grant will allow Otsuka to further evaluate OPC-167832 as part of a novel trial design combining multiple-ascending-dose and early-bactericidal-activity studies for evaluation in drug susceptible TB patients, scheduled to begin in the fourth quarter of 2018. It will also allow Otsuka to explore a combination of OPC-167832 plus delamanid for future evaluation of pan-TB regimens. Results from delamanid’s phase 3 study (trial 213) demonstrated that patients achieved faster sputum culture conversion over 6 months when delamanid was added to a WHO-recommended optimized background regimen (OBR) than placebo plus OBR.2 Following analysis of these results, WHO reaffirmed that the current interim guidance on delamanid remains in place and the conditions for use remain the same, stating the results “provided reassurance of delamanid as a relatively safe drug compared to other second-line medicines.”3
“Otsuka is honored to be part of this exciting project with the Bill & Melinda Gates Foundation,” said Keiso Yamasaki, TB global project leader. “The challenge of eliminating TB is too large for any single company, institution or government to take on alone. Working together, the successful development of a pan-TB regimen could be a real game-changer in this field.”
OPC-167832 is an anti-TB compound discovered and currently under investigation by Otsuka. It inhibits the enzyme Decaprenylphosphoryl-β-D-ribose 2’-oxidase (DprE1), which is connected to synthesis involving mycobacterial cell walls. This is a different mechanism of action from other currently available anti-TB drugs. In vivo studies in mice suggest that OPC-167832 plus delamanid-containing regimens have the potential to shorten therapy and improve outcomes in drug-susceptible TB and multidrug-resistant TB.4
Delamanid inhibits the synthesis of mycolic acid, an essential component of mycobacterial cell walls. Regulatory approval has been received in the EU, Japan, South Korea, Hong Kong, the Philippines, Turkey and India where it is marketed as Deltyba™. Delamanid is not yet approved for use in the U.S.
Delamanid was studied in a randomised, placebo-controlled phase 2 trial that included a 2-month treatment period and a 1-month follow-up of 481 MDR-TB patients (trial 204), with 213 patients continuing to a 6-month open-label treatment trial (trial 208), and concluding with a 24-month follow-up study of 421 out of the originally randomized 481 patients (trial 116). Adding 100 mg delamanid twice daily to OBR was associated with a statistically significant 53% increase (p=0.008) in the percentage of patients achieving SCC at 2 months (64/141, 45.4%) compared to those with placebo added (37/125, 29.6%).5 Mortality rates were 1.0% (2/192) in patients receiving delamanid for at least 6 months compared with 8.3% (19/229) for those receiving delamanid for 2 months or no delamanid (p<0.001).6
Clinical trial results demonstrated that delamanid demonstrated a comparable adverse event profile between delamanid and placebo treatment groups with the exception of electrocardiogram QT prolongation in 9.9% (16/161) of patients compared to 3.8% (6/160) of patients receiving placebo plus OBR. This was not accompanied by any clinical symptoms such as syncope or arrhythmias.5
Publication of phase 3 results on the safety and efficacy of delamanid is expected to be completed later in 2018 and a pediatric investigational program is currently underway.
Otsuka is a global healthcare company with the corporate philosophy: “Otsuka-people creating new products for better health worldwide.” Otsuka researches, develops, manufactures and markets innovative products, with a focus on pharmaceutical products for the treatment of diseases and nutraceutical products for the maintenance of everyday health.
In pharmaceuticals, Otsuka is a leader in the challenging area of mental health and also has research programs on several under-addressed diseases including tuberculosis, a significant global public health issue. These commitments illustrate how Otsuka is a “big venture” company at heart, applying a youthful spirit of creativity in everything it does.
Otsuka Pharmaceutical Development & Commercialization, Inc. is an indirect subsidiary of Otsuka Pharmaceutical Co., Ltd. headquartered in Tokyo, Japan. The Otsuka group of companies employed 45,000 people worldwide and had consolidated sales of approximately US $11 billion in 2016.
All Otsuka stories start by taking the road less travelled. Learn more at https://www.otsuka.co.jp/en.
1 World Health Organization. Target regimen profiles for TB
treatment: candidates: rifampicin-susceptible, rifampicin-resistant and
pan-TB treatment regimens. WHO/HTM/TB/2016.16
2 Geiter, L. (2017, October) Delamanid trial 213: Summary of results. Presented at 48th Union World Conference on Lung Health, Guadalajara, Mexico
3WHO position statement on the use of delamanid for multidrug-resistant tuberculosis
4 Otsuka unpublished data.. SN037927-RN031553-Study in Mouse Chronic TB Model
5 Gler MT, et al. Delamanid for multidrug-resistant pulmonary tuberculosis. New England Journal of Medicine 2012; 366: 2151–2160.
6 Skripconoka V, et al. Delamanid improves outcomes and reduces mortality in multidrug-resistant tuberculosis. European Respiratory Journal 2013; 41: 1393–1400.