Impact case study database

International approval of tasimelteon (HETLIOZ®) for the treatment of Non-24-Hour Sleep-Wake Rhythm Disorder (N24HSWRD) in people with total blindness

On 31 January 2014, the U.S. Food and Drug Administration (FDA) approved tasimelteon (HETLIOZ^®) as the first treatment for N24HSWRD in people with total blindness under the orphan drug pathway. The FDA committee agreed that the drug had “proven to be effective and safe for patients with non-24 ” [S1]. On 7 July 2015, the European Medicines Agency (EMA) also approved HETLIOZ^® for the treatment of N24HSWRD in totally blind adults in 28 European Union countries, as well as Iceland, Lichtenstein and Norway [S2]. HETLIOZ^® was launched commercially in the U.S in April 2014 and Germany in August 2016 [S3]. These approvals mark a paradigm shift with the introduction of a new drug class: HETLIOZ^® is the first and only drug to date that is approved based on its ability to reset the circadian pacemaker to treat a circadian rhythm disorder.

Research conducted by Professor Skene and her team into the effectiveness of melatonin to entrain free-running circadian rhythms in people with total blindness directly informed the clinical trials design and subsequent licensing application of tasimelteon (HETLIOZ^®) [S4]. The protocol design of these clinical trials replicated the methodology and outcomes developed at the University of Surrey to assess circadian entrainment. Data sets shared with Vanda Pharmaceuticals by the University of Surrey were used to optimise the clinical study design (e.g., informing the power calculation) of these clinical trials and raw sleep/nap and cycle length data from Professor Skene’s 0.5 mg melatonin study [R2] were used to validate novel markers to assess the effectiveness of tasimelteon (HETLIOZ^®) in treating N24HSWRD [S4, S5]. Professor Skene also provided expert evidence in support of Vanda Pharmaceutical’s application to the EMA in May 2015 [S6].

The introduction of this FDA/EMA approved treatment for N24HSWRD has benefitted patients and raised awareness of this debilitating disorder. At the time of designation (2015), the EMA estimated the number of patients affected by N24HSWRD as between 6,000-112,000 people (1.5 and 2.2 in 10,000) in Europe. Prior to the designation of HETLIOZ^®, no satisfactory therapies were authorised in the EU for the treatment of N24HSWRD [S2]. Professor Skene has increased awareness and public understanding of this and other rare sleep disorders through a series of public talks (i.e., Royal Institute, Hay Festival, Design Museum), radio and newspaper interviews (i.e., Radio 4 , The Observer, The Guardian) and television documentaries (i.e., Secrets of the Body Clock with Terry Wogan, BBC One; Horizon, BBC2) [S7].

Commercial growth and continued innovation

Quarter end financial results for the first full quarter (third) following the launch of HETLIOZ^® in the US in April 2014 show sales grew to $5.2 million with over 600 new patient prescriptions written during that quarter. Vanda President and CEO Mihael Polymeropoulos said “Our innovative approach to the commercialisation of HETLIOZ^® for [N24HSWRD] has yielded impressive third quarter revenue. We are developing a robust commercial engine that has just begun to access the [N24HSWRD] market in the US by creating awareness leading to diagnosis and treatment.” Sales of HETLIOZ^® have continued to grow year on year with net product sales of $38.6 million in the fourth quarter of 2019, an increase of 19% from the fourth quarter of 2018 ($32.4m). Full-year net product sales for 2019 were $143 million, an increase of 23% from 2018 ($115.8m) [S3].

Professor Skene and her team continued to work in partnership with Vanda Pharmaceuticals to support their innovation into new markets. Professor Skene’s expertise in the use of melatonin to entrain ‘free-running’ circadian rhythms gained through her research [R1, R2, R3] was called upon by Vanda Pharmaceuticals to inform the protocols for clinical trials of HETLIOZ^® for a broader range of indications resulting from circadian desynchronisation including jetlag, metabolic disorders, and other sleep-wake disorders. Commercial research undertaken at the Surrey Clinical Research Centre (University of Surrey) resulted in an FDA application for HETLIOZ^® in the treatment of jetlag in April 2018. A further New Drug Application (sNDA) for HETLIOZ^® in the treatment of sleep disorders in patients with Smith-Magenis Syndrome (SMS), another rare genetic disorder has also been filed. Phase III testing is currently underway for paediatric N24HSWRD and delayed sleep phase disorder (DSPD). This innovation has risen directly from the original research conducted by the Section of Chronobiology.