Impact case study database

Context

UoM researchers led an international work programme delivering treatments for Mucopolysaccharide and related lysosomal diseases. Although rare, one baby born every eight days globally will be diagnosed with an MPS or related disease. These multi-organ storage diseases cause progressive physical disability and, in many cases, severe progressive mental deterioration resulting in childhood death.

Outputs from UoM programme have led to:

1. Clinical impact from trials run in Manchester including market authorisation of new treatments.

2. Economic impact through establishing a company (Orchard Therapeutics) to test new gene therapies, and licencing of two Manchester gene therapies to US companies (AvroBio, Phoenix Nest) (MPSII, MPSIIIC), with the advantage of increased enzyme expression from a single treatment.

Reach and significance of the impact

Enabling new treatments for lysosomal storage disorders

Over the past six years, Manchester recruited five global first patients and the majority of patients onto 13 multicentre lysosomal storage disease studies. Two treatments gained market authorisation as a direct result of UoM work in these trials, leading to >90 LSD patients in England and >1,000 worldwide being treated [A].

Example 1: LAL-D

Prior to Sebelipase Alfa availability (marketed as Kanuma, Alexion Pharmaceuticals, Inc.), treatment options centred upon supportive interventions, including blood transfusions and nutritional supplementation, but average infant life expectancy was less than four months from diagnosis. Through UoM’s research, in collaboration with other centres [1], ERT Sebelipase Alfa for LAL-D has been approved worldwide: European Medicines Agency (EMA) September 2015) [Bi]; US Food and Drug Administration (FDA) December 2015 [Bii]; Japan’s Ministry of Health, Labour and Welfare (MHLW) March 2016 [Biii]; and Health Canada December 2017 [Biv].

Albie, diagnosed with LAL-D at two months, took part in the Kanuma trial, commencing in 2011. His mother Charlotte stated, “ After several weeks of treatment, Albie gradually began to put on weight and improve” [C]. Prior to this treatment, most infants with LAL-D died before reaching six months of age. Albie is now eight years old.

Sebelipase Alfa was initially rejected by the National Institute for Health and Care Excellence (NICE) in 2017 for financial reasons although NICE committee “ recognised that sebelipase alfa is a potentially life-saving treatment in this population, and there is a compelling clinical need” [Di]. The decision is under appeal but the schedule has been affected by Covid-19 and does not currently have a timeline for restarting [Dii].

Alexion reported Kanuma net product sales of USD112,200,000 in 2019, compared to USD92,000,000 in 2018 and USD65,600,000 in 2017, representing a 22% and 40% increase respectively [E].

Example 2: Morquio syndrome/MPS IVA

Resulting from UoM research [2,3], ERT for Morquio syndrome involving Elosulfase Alpha (marketed as Vimizim, Biomarin Pharmaceuticals) has been approved worldwide: US FDA February 2014 [Fi]; EMA April 2014 [Fii]; Health Canada July 2014 [Fiii]; National Health Surveillance Agency Brazil , MHLW Japan, Australian Therapeutic Goods Administration December 2014 [Fiv] and National Medical Products Administration, China June 2019 [Fv]. In all these countries, Vimizim was the first treatment approved for Morquio A syndrome. At the time of EU approval, Chief Executive of the MPS Society, (UK) said, " For patients with Morquio A disease now having a specific drug treatment option provides real hope after decades of sadness and loss for so many families" [Fii].

In December 2015, NICE recommended funding Elosulfase Alfa treatment for Morquio A syndrome [G]. At the time of NICE evaluation (2015), there were 88 people living with MPS IVA in England, with ~3 new diagnoses per year. The company and patient group noted that 74–77 of these were anticipated to be eligible for ERT with Elosulfase Alfa [G].

Biomarin annual reports record Vimizim sales of USD544,300,000 in 2019, up from USD482,000,000 (2018) and USD413,300,000 (2017), a 13% and 17% increase respectively year on year. Vimizim is only used to treat Morquio A [H].

UoM research helped build commercial capacity in the UK and overseas

Gene therapy for MPS IIIA (Manchester preclinical programme) [4] was one of three critical founding programmes for UK-based Orchard Therapeutics, founded in 2015 to improve the lives of patients suffering from rare genetic diseases by designing autologous ex vivo gene therapies. Bigger, Jones and Wynn are members of Orchard’s Scientific Advisory Board and UoM remains a critical collaborator. The MPS IIIA programme (led by Bigger), was critical in the start-up of the company. Orchard CEO stated, “ The University’s research expertise and development work was integral to our success in securing $33 million [USD33,000,000] Series A financing, led by F-Prime Capital, which allowed us to successfully launch the company in May 2016” [Ii]. MPS IIIB [5] was licenced to Orchard Therapeutics in November 2017. Orchard CEO further confirmed, “ The University continues to contribute to the success and growth of our company including our collaboration on a clinical trial for MPSIIIA. The number of people employed by Orchard has risen from 33 in 2017 to over 250 (of which around 85 based are (sic) in the UK) by December 2019” [Ii]. Orchard offered initial shares to the public on the US stock exchange in October 2018 with a market value of USD1,180,000,000 [Iii]. In January 2019 a patient was treated on a compassionate basis with the MPSIIIA genetic therapy and three patients have since been treated on a UoM-sponsored trial. Ten months on from compassionate treatment, Royal Manchester Children’s hospital reported the patient was ‘doing well’ [Ji]. Preliminary clinical trial data showing treatment is safe and well-tolerated was presented in December 2020 at American Society of Hematology Annual meeting [Jii].