CHMP Grants Positive Opinion for Expanded Use of Otsuka’s Deltyba ® (delamanid) in Children and Adolescents Weighing at Least 30kg Treated for Pulmonary Multi-drug Resistant Tuberculosis

Otsuka Novel Products GmbH (ONPG), a subsidiary of Otsuka Pharmaceutical Co., Ltd., is pleased to announce that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) recommends approval of extension of the indication for Deltyba^® (delamanid) for children. This means Deltyba^® (delamanid) is recommended by the CHMP for use as part of an appropriate combination regimen for pulmonary MDR-TB in adults, adolescents and children with a body weight of at least 30kg when an effective treatment regimen cannot otherwise be composed for reasons of resistance or tolerability.

According to the current World Health Organization Global TB Report, an estimated 1.1 million children (0-14 years of age) fell ill with TB in 2018.² Each year, approximately 25,000-32,000 children fall ill with MDR-TB. Of these, only 3-4% are diagnosed and treated and consequently, approximately 21% of children with MDR-TB are likely to die.¹

New global targets set at the UNs High Level Meeting on TB two years ago include treating 115,000 children with drug-resistant TB in the five-year period 2018-2022.²

“This positive CHMP opinion is a further milestone in Otsuka’s mission to address unmet medical needs – particularly for the most vulnerable and underserved populations such as children with MDR-TB,” says Robert Dornheim, CEO of Otsuka Novel Products GmbH. “We look forward to working with the TB community to further enhance access of delamanid in this age group.”

The positive opinion for the label extension is based on data accumulated from the first two paediatric patient groups enrolled in delamanid paediatric trials: Study 242-12-232 (Trial 232) - a phase 1, open label, uncontrolled, multiple-dose, age de-escalation trial to assess pharmacokinetics and safety of delamanid administered for 10 days to paediatric patients with presumed or confirmed MDR-TB receiving a WHO-recommended regimen and Study 242-12-233 (Trial 233) - a phase 2, open-label, multiple-dose trial to assess the safety, tolerability, pharmacokinetics, and efficacy of delamanid plus a WHO-recommended MDR-TB regimen in paediatric patients with MDR-TB over a 6-month treatment period. Thirteen patients were enrolled in Trial 232: 7 in Group 1 (12 – 17 years) and 6 in Group 2 (6– 11 years). All patients who completed the trial were enrolled in Trial 233.^3,4

The primary objectives of Trial 233 were to assess the long-term safety and tolerability of delamanid and to characterise the pharmacokinetics of delamanid. Overall, delamanid was well tolerated in this cohort of paediatric patients and most frequently reported adverse events were headache (8 subjects [61.5%]), upper respiratory tract infection (7 subjects [53.8%]), and arthralgia (5 subjects [38.5%]). No deaths occurred during treatment with delamanid in both age groups.³ The frequency, type and severity of adverse reactions in children are expected to be the same as in adults.

Secondary trial objectives of Trial 233 included evaluation of delamanid efficacy: 12 of the 13 (92.3%) subjects had a favourable 24-month WHO final treatment outcome (cured or treatment completed) and 1 subject (7.7%) did not complete the study.³

About Deltyba^® (delamanid)

Deltyba^® (delamanid) inhibits the synthesis of mycolic acid, an essential component of mycobacterial cell walls.⁵ It has been in use since 2014 as part of an appropriate combination regimen for pulmonary MDR-TB in adult patients when an effective treatment regimen cannot otherwise be composed for reasons of resistance or tolerability.⁶ It has exhibited anti-TB efficacy and a favourable safety profile in multiple Otsuka-sponsored clinical trials, including two Phase 2 studies, an open-label Registry (Trials 204/208/116), and one Phase 3 study (Trial 213).^7-9

About MDR/RR-TB

In 2018, an estimated 484,000 people acquired rifampicin-resistant TB (RR-TB), and of these, 78% had MDR-TB, a type of TB resistant to rifampicin and isoniazid.² TB is one of the most dangerous infectious diseases and drug-resistant TB is considered a global public health emergency by the World Health Organization.² New treatment options for such patients are urgently needed. At the same time, it needs to be ensured that TB drugs remain effective for as long as possible, especially since there have only been a few new medications developed to treat drug-resistant forms of TB in the last 50 years.^10,11

About Otsuka Novel Products GmbH

Otsuka Novel Products GmbH (ONPG), based in Munich, Germany, is dedicated to finding innovative solutions to fight the global pandemic of tuberculosis (TB). As the marketing authorization holder for Deltyba^® (delamanid) in the European Union, ONPG works in collaboration with other Otsuka Group companies, non-governmental organisations and other stakeholders, to expand access to Deltyba^® (delamanid) and fight MDR-TB.

ONPG is a part of Otsuka Pharmaceutical Company, Ltd., a subsidiary of Otsuka Holdings Co., Ltd. headquartered in Tokyo, Japan. Otsuka Pharmaceutical 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 to meet unmet medical needs and nutraceutical products for the maintenance of everyday health. Further information is available at www.otsuka-onpg.com.

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Date of preparation: September 2020
ONP-DEL-2000013

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¹ Jenkins H, et al. The burden of multidrug-resistant tuberculosis in children. Int J Tuberc Lung Dis. 2018; Vol.22(5)
² World Health Organization. Global Tuberculosis Report 2019. Available at: https://apps.who.int/iris/bitstream/handle/10665/329368/9789241565714-eng.pdf?ua=1(Last accessed: September 2020)
³ EudraCT. https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-004620-38/results (Last accessed: September 2020)
⁴ EudraCT. https://www.clinicaltrialsregister.eu/ctr-search/search?query=242-12-232 (Last accessed: September 2020)
⁵ Matsumoto M, et al. OPC-67683, a nitro-dihydro-imidazooxazole derivative with promising action against tuberculosis in vitro and in mice. PLoS Med. 2006 Nov;3(11):e466
⁶ Deltyba^® (delamanid) EU Summary of Product Characteristics (April 2020). Available at: https://www.ema.europa.eu/en/documents/product-information/deltyba-epar-product-information_en.pdf (Last accessed: September 2020)
⁷ Gler M, et al. Delamanid for multidrug-resistant pulmonary tuberculosis. N Engl J Med 2012; 366: 2151-2160.
⁸ Skripconoka V, et al. Delamanid improves outcomes and reduces mortality in multidrug-resistant tuberculosis. Eur Respir J. 2013; 41:1393-400.
⁹ von Groote-Bidlingmaier F, et al. Efficacy and safety of delamanid in combination with an optimised background regimen for treatment of multidrug-resistant tuberculosis: a multicentre, randomised, double-blind, placebo-controlled, parallel group phase 3 trial. Lancet Respir Med 2019; 7(3):249-259.
¹⁰ Access to Medicine Foundation report "Ending the burden of HIV, malaria and TB in children". June 2020, Available at: https://accesstomedicinefoundation.org/media/uploads/downloads/5ee1fd19b7187_ATMF_Ending_the_Big3_on%20Children-Full_09June20.pdf (Last accessed: September 2020)
¹¹Ignatius E. and Dooley K. New Drugs for the Treatment of Tuberculosis Clin Chest Med. 2019: 40(4):811-827.

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Contact information

Marc Destito
Senior Director, Global TB Projects
mdestito@otsuka-onpg.com
+41 78 881 03 22