Impact case study database

Impact on the health and wellbeing of people

Innovative Treatments: Cox and colleagues drove the successful clinical trials of the first compound, miglustat, for the treatment of sphingolipid diseases: this led directly to clinical approval in Europe in 2009 and subsequently in 44 additional countries, including the USA in August 2014 [A]. In 2018, the FDA approved a miglustat generic for the treatment of sphingolipid-driven diseases [A]. The effectiveness of oral miglustat treatment for Gaucher disease motivated the development of eliglustat as a second generation, potent oral treatment (Genzyme Corp, later Sanofi Genzyme). Cox was involved as an advisor, a member of the safety monitoring committee and then Chief Investigator of the pivotal, large Phase III that showed the efficacy of eliglustat [5] and ultimately led to its European Medicines Agency recommendation in 2018 [A].

As a direct result of Cox’s research, Sanofi Genzyme has supplied eliglustat (approved as Cerdelga™) for clinical use since 2014 and was approved for prescription by The National Institute for Health and Care Excellence (NICE) (HST5) [B] and the Scottish Medicines Consortium (1277/17) in 2017. Eliglustat was made available in NHS England (September 2017) and NHS Scotland (February 2018) [C]. Of the 250 Gaucher patients in the UK national cohort study, within the first two years since UK authorization, 70 patients are taking the oral substrate-reduction therapy. Worldwide, of 7,000 patients in the international registry, more than 1,200 are now taking eliglustat and it has been approved in more than 55 countries, demonstrably improving the quality of life of these patients [D] and [4,5]; following one year of eliglustat, 98% of patients expressed a preference for oral therapy and the main reason cited was convenience [5]. Patient testimony has demonstrated the improved quality of life for patients, as Adele, a Gauchers Type I patient describes her experience in the Gaucher’s Association April 2017 Newsletter: “ Presently I am still taking Eliglustat and […] I can honestly say that I have never felt better, which allows me to do all the things I have always wanted to do. Mostly this involves daily long walks with my dog.” [G].

Novel Diagnostics: The PARC-CCL-18 biomarker discovered by Cox is now used widely within standardised assays for clinical monitoring of Gaucher disease. This Gaucher biomarker has positively affected clinical practice, as clinicians have been able to use these proteins as biomarkers in diagnosing disease and importantly, in following treatment response in Gaucher disease and other lysosomal diseases. This has had a global impact on treatment and patient benefit for those suffering from these lysosomal diseases, because it provides clinicians with the means to compare and monitor dynamic therapeutic responses to a range of treatments with distinct modes of action [E and F]. Indeed, Jeremy Manuel OBE LLB, Founder of the UK Gaucher’s Association and Honorary President and co-Founder of the International Gaucher Alliance, notes that “ It was Prof Cox who initiated the national strategy of centres for the treatment Gaucher patients which subsequently expanded to cover all Lysosomal diseases patients and he continues to be a clear and guiding voice on the ongoing advisory groups responsible for developing and delivering National Protocols and the best possible for treatment for patients (where this a treatment and management of conditions) where there is none.” [F]

Patient education and empowerment: Building on decades of support for the UK Gaucher’s Association since its inception, Cox helped generate a forum and advocacy group for families and patients suffering from Tay-Sachs and Sandhoff diseases. As a Patron, Cox supported establishment of the UK Cure Tay-Sachs Foundation in 2011 and subsequently in 2014 the formation of the European Tay-Sachs and Sandhoff disease Charity Consortium. He now serves as the Consortium’s Medical Advisor [F].

Cox was also instrumental in the establishing the International Gaucher Alliance in 2018. The Alliance is an umbrella group representing the interests of Gaucher patients in 55 countries. Cox has consistently raised public awareness of this disease and supported the formation of EU Charities (Europe and elsewhere) [F], as verified by Jeremy Manuel, who has described Cox’s influence as follows: “ He has always championed the involvement of Patient advocates in all areas of clinical, scientific and public life and inspired the patient community to partner with the clinical and scientific community in their efforts to improve the lot of Gaucher patients, and promoted the involvement of patients to industry, regulators and those responsible for managing the delivery of healthcare and paying for access to treatment. All Doctors promote the cause of the patient before them not all seek to improve and enhance the position of their cohort on a National and Global basis.” Cox remains actively involved with these groups and provides education and updates to patients via their communication channels [G].

Impact on practitioners and the delivery of professional services

Cox’s research and policy creation has provided clinicians with new treatments, ways of monitoring these diseases and better guidelines for clinical management. Patients have benefitted from the following impacts on practitioners:

• In 2014 the FDA approved eliglustat.

• In 2018 the FDA approved a miglustat generic from Amerigen Pharmaceuticals for the treatment of Type I Gaucher disease [A].

• In 2018, the European Medicines Agency recommended eliglustat (tartrate) for the treatment of Type I Gaucher disease [A].

• Eliglustat is now a first-line oral treatment of choice for patients for adults with Type I Gaucher disease [B and C].

• Phase I/II Trials are underway with a derivative called venglustat, an oral treatment which is more effective at penetrating the brain in patients with sphingolipid derangements in Fabry disease and neuronopathic Gaucher disease (Cox is PI). In addition, he leads the European initiative with EMA as CI in the Phase I/II trial in late-onset Tay-Sachs and Sandhoff diseases (announced Jan 2020). Phase I and II clinical trials for Venglustat in adults with Late-onset Tay-Sachs and Sandhoff diseases are currently being conducted and Phase III extension studies in Neuronopathic Gaucher disease type 3 are currently being run (AMETHSIST [ClinicalTrials.gov Identifier: NCT04221451] and LEAP [NCT02843035] trials).

Impact on commerce and the economy

Global drug sales: Initial approval of miglustat (Zavesca®) priced at USD26,820 per month, per patient, had 2016 world sales of USD104,000,000 [H]. Actelion (makers of Miglustat) were then bought by Johnson & Johnson for USD30,000,000,000 [H]. In April 2018 the U.S. FDA approved Amerigen Pharmaceuticals’ generic form of Miglustat; and its partner Miglustat Dipharma, a generic, is used in 33 countries – the first generic approval for miglustat (Zavesca®) [H].

Commercial impact has also been generated through the global sales of eliglustat (Cerdelga®) as sales over the REF impact assessment period have eclipsed EUR773,000,000 [H]. Following its FDA approval in August 2014, eliglustat sales totalled EUR4,000,000 in Qs 3 and 4 of that year. Sales have continued to rise year on year, and in Q1 of 2020, total sales were EUR53,000,000, of which 53% was in the USA and 41% was in Europe [H].

Biotech spinoff company: Cox established Cambridge Gene Therapy (Companies House No. 11112130) in December 2017, which aims to develop and broaden the clinical programmes targeting lysosomal diseases and in particular using pioneering gene therapy as a treatment for Tay-Sachs disease, which is currently incurable [I]. He has secured seed funds of GBP500,000 from Cambridge Enterprise to support pivotal clinical trials and full translational development of this research [J].