FDA endorses 505(b)(2) route for DITEST™
Pivotal data anticipated in 2024 to support NDA filing in the US
Diurnal Group plc (AIM: DNL), the specialty pharmaceutical company targeting patient needs in chronic endocrine (hormonal) diseases, announces positive feedback from a pre-Investigational New Drug (IND) meeting with the US Food and Drug Administration (FDA) in relation to DITEST™ (native oral testosterone formulation), being developed by the Company as a treatment for male primary and secondary hypogonadism. The FDA has confirmed that DITEST™ can progress to a New Drug Application (NDA) via the 505(b)(2) route.
The consequence of this decision is that the registration programme for DITEST™ required for submission of an NDA (New Drug Application) and marketing approval could comprise of only two further clinical studies: a multiple ascending dose study followed by a single pivotal Phase III trial. The Company expects that data from the Phase III study could be available as early as 2024 to support an NDA filing in the US.
The estimated $4.8 billion market in the US and Europe for testosterone-based products for the treatment of hypogonadism is dominated by topically available products. However, these can be inconvenient and messy for patients, while oral modified testosterone products (testosterone undecanoate) display a variability in absorption and have a requirement for a high-fat meal to achieve therapeutic testosterone levels1. DITEST’s novel formulation is designed to increase oral bioavailability and removes the requirement to be taken with a high-fat meal.
The FDA advice follows the Company’s Phase I proof-of-concept clinical trial in the target patient group of 24 adult men with primary or secondary hypogonadism. This study evaluated the pharmacokinetics, safety and tolerability of DITEST™ in 24 subjects2.The successful outcome of the study was reported on 20 November 2019 and confirmed the positive findings from the Company’s in vivo pre-clinical studies.
Martin Whitaker, CEO of Diurnal, commented:
“We are delighted by the outcome of our meeting with the FDA. The ability to develop DITEST™ in the US using the 505(b)(2) pathway significantly accelerates the timeline to its potential approval and reduces the cost of the programme.
We believe DITEST™ could be an effective and differentiated therapy to address the significant unmet patient needs of the 60 million men, globally, who are affected by hypogonadism3. DITEST™ is the next clinical-stage product in our pipeline after Alkindi® and Chronocort® and is a key part of our ambition of becoming one of the world’s leading endocrinology specialty pharma companies.”
 Schnabel et al (2007)
2Clinical Trials ID NCT02966652
3 Datamonitor Report 2015
This announcement contains inside information for the purposes of Article 7 of Regulation (EU) 596/2014 (MAR).
For further information, please visit www.diurnal.co.uk or contact:
Diurnal Group plc +44 (0)20 3727 1000
Martin Whitaker, Chief Executive Officer
Richard Bungay, Chief Financial Officer
Panmure Gordon (UK) Limited (Nominated Adviser and Joint Broker) +44 (0) 20 7886 2500
Corporate Finance: Freddy Crossley, Emma Earl
Corporate Broking: James Stearns
FTI Consulting +44 (0)20 3727 1000
Victoria Foster Mitchell
Notes to Editors
About the 505(b)(2) regulatory pathway
The 505(b)(2) route in the US relies on published literature and other non-Company studies to support a marketing application and can significantly accelerate the time to approval, compared to new chemical entities.
Hypogonadism results from failure of the testes (primary gonadal failure) or from failure of stimulation by the pituitary (secondary hypogonadism) resulting in testosterone insufficiency. In primary hypogonadism, failure of the testes can be congenital (inherited) or acquired during life due to a variety of causes (failure of the testes to descend into the scrotum, inflammation due to infections such as mumps, chemotherapy or radiotherapy affecting the testes, and following removal of the testes for testicular tumours). Secondary hypogonadism usually results from a benign tumour of the pituitary gland that causes hypopituitarism and may occasionally be congenital.
The hypogonadism market is a large and fragmented market. Diurnal estimates that in Europe and the US the market opportunity is around $4.8 billion per annum. Topical (gel) formulations are the current market leaders due to low bioavailability of testosterone in the body when administered by the oral route. However, these topical formulations have compliance and administration issues. Other testosterone replacement therapies for hypogonadism include intramuscular injections, testosterone patches and the only currently available oral forms are modified testosterones (such as testosterone undecanoate) that have limited label scope, well-documented pharmacokinetic variability, a requirement to be taken with a high fat meal and safety concerns1.
Therefore, Diurnal believes that there is a patient need for an oral (native) testosterone preparation.
DITEST™ is a novel formulation developed by Diurnal comprising native testosterone adapted for oral delivery for the treatment of hypogonadism. The main challenge with oral delivery of native testosterone is that, whilst the hormone undergoes rapid and complete absorption, there is considerable metabolism in both the gut wall and during first hepatic pass which accounts for up to 98% reduction in testosterone bioavailability (the amount of drug in the body that is able to have an active effect). Diurnal’s approach is a proprietary lipid-based formulation that aims to provide improved bioavailability of testosterone. An additional potential feature of the native testosterone formulation demonstrated in both preclinical studies and now in this clinical study is that it shows similar absorption and bioavailability in both the fed and fasted state and therefore potentially can be taken without a substantial meal, which is a problem associated with alternative oral modified-testosterone formulations.
Patents protecting DITEST™ have already been granted in the US, Europe and other major territories worldwide.
About Study DITEST-001
The DITEST-001 study was a Phase I proof-of-concept clinical trial in the target patient group of 24 adult men with primary or secondary hypogonadism which evaluated the pharmacokinetics, safety and tolerability of DITEST™ and to compare these properties to an existing testosterone undecanoate therapy in hypogonadal patients.
The primary endpoint of the trial compared the rate and extent of absorption of testosterone from a single dose of DITEST™ 120mg with a single dose of testosterone undecanoate 80mg in the fed state in hypogonadal men. In this respect, DITEST™ was shown to achieve testosterone levels within the healthy young male adult normal range after oral administration, with levels that were less variable than testosterone undecanoate.
Secondary endpoints demonstrated that there was no impact on the rate and extent of absorption of testosterone from DITEST™ 200mg whether taken with either food or in the fasted state, representing a major difference with testosterone undecanoate. The safety and tolerability of two different doses of DITEST™ were also assessed in the study: there were no serious adverse events in the DITEST™ arm of the study, and levels of the potent testosterone derived androgen, dihydrotestosterone (DHT), were lower than with testosterone undecanoate.
About Diurnal Group plc
Founded in 2004, Diurnal is a UK-headquartered, European specialty pharma company developing pharmaceutical products for the global market for the life-long treatment of chronic endocrine conditions, including congenital adrenal hyperplasia and adrenal insufficiency. Its expertise and innovative research activities focus on circadian-based endocrinology to yield novel product candidates in the rare and chronic endocrine disease arena.
For further information about Diurnal, please visit www.diurnal.co.uk
Date of Preparation: June 2020 Code: CORP-GB-0061
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