Otsuka, Mylan to Commercialize Delamanid

Otsuka Pharmaceutical and Mylan have entered into a license agreement between their subsidiaries to commercialize delamanid for the treatment of adults with pulmonary multidrug-resistant tuberculosis (MDR-TB) in low- and middle-income countries. Delamanid was discovered and developed, and is currently marketed by Otsuka under the brand name Deltyba.

Under the terms of the agreement, Mylan has been granted an exclusive license by Otsuka to prioritize access to Deltyba in South Africa and India. Both countries are considered by the World Health Organization (WHO) as among the highest-burden countries for MDR-TB and TB/HIV co-infection, with over 150,000 estimated new cases of MDR-TB/rifampicin-resistant TB in 2015. The Drug Controller General of India (DCGI) granted approval to Mylan to market Deltyba in India, and registration is under way in South Africa.

Mylan is anticipated to further exercise exclusive commercial rights and registration responsibilities in additional countries, including many other high MDR-TB burden countries where Otsuka does not have a commercial presence. The agreement announced today also allows both companies to enter into discussions and feasibility studies for a technology transfer plan, enabling Mylan to manufacture and distribute Deltyba for these markets in the future.

"Otsuka is a global leader in TB research and development and Mylan is a recognized leader in the provision of high-quality medicines for infectious diseases in many developing countries," said Tatsuo Higuchi, president and representative director. "Given our respective experience in the field, our two companies are well positioned to work together in the fight against MDR-TB."

Deltyba is one of two anti-tuberculosis medicines recently approved, after more than 40 years of treatment with the same agents. It is registered in the European Union, Japan, the Republic of Korea, Hong Kong, S.A.R., China, Turkey and India. Since regulatory approval, more than 4,000 treatment courses of Deltyba have been shipped for use in over 50 countries. Otsuka recently launched a novel, pre-approval access program in South Africa administered by the Department of Health and a similar rollout program in India is ready to begin.

The efficacy of Deltyba was studied in a large, randomized, placebo-controlled phase 2 trial that included a 2-month treatment period and a one-month follow-up of 481 MDR-TB patients (Trial 204), with 213 patients continuing to a six-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 Deltyba twice daily to a WHO-recommended 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%).2 The reported mortality rate was lower in patients receiving Deltyba for at least 6 months (2/192 (1.0%) compared with those receiving Deltyba for two months or no Deltyba  (19/229 (8.3%); p<0.001).

Clinical trial results demonstrated that Deltyba is well tolerated with adverse events evenly distributed in the Deltyba and placebo treatment groups with the exception of QT prolongation. Electrocardiogram QT prolongation was reported in 9.9% (16/161) of patients receiving Deltyba as 100 mg twice daily 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.