New Medicines

Stargardt's disease


New molecular entity

Development and Regulatory status

Phase II Clinical Trials
Phase II Clinical Trials
Oct 20Remains PII in Astellas pipeline [9].
Apr 19Has orphan drug status in EU & US. Has been granted ATMP status by the EMA [6].
Jan 19PII for SMD and dry AMD [5].


Allogeneic retinal pigment epithelial (RPE) cells dervied from embryonic stem cells given by uniocular subretinal injection
Stargardt's disease, with or without fundus flavimaculatus, is the most common hereditary dystrophy affecting the central retina, occurring in 1 in 8,000-10,000 people. Also known as juvenile macular dystrophy: this is one of the two most common forms of inherited macular degeneration. It accounts for 7% of all retinal dystrophies. It is a progressive, bilateral atrophic macular dystrophy characterised by perimacular and peripheral dirty grey-yellow spots (fundus flavimaculatus) [1].
Stargardt's disease
Subretinal injection

Trial or other data

Apr 20PI/II safety study (NCT02941991) completed in October 2019; this followed patients for 5 years. Other completed safety studies followed patients for 1 to 5 years (NCT02445612) and 1 year (NCT01469832) [8].
Mar 20A 15-year PI/II safety surveillance study is enrolling by invitation patients who have been treated with hESC-RPE cell therapy in an Astellas Institute for Regenerative Medicine (AIRM) sponsored clinical trial in macular degenerative disease (NCT03167203). The study started in Jan 18 and is enrolling adults from the US and UK (Site GB44001; no further details provided). It is due to complete Dec 29 [8].
Mar 20PI/II safety study (NCT02941991) completed in October 2019; this followed patients for 5 years. Other completed safety studies followed patients for 1 to 5 years (NCT02445612) and 1 year (NCT01469832) [8].
Dec 19UK trial sites; NCT02941991 (Moorfields, Newcastle), NCT01469832 (Edinburgh, Moorfields, Newcastle)
Jun 19NCT02445612 Pi/II trial completed [7]
Mar 19PI/II study is continuing (NCT02941991) & expects to complete collection of primary outcome data in Dec 19 [2].
Nov 18PI/II study (NCT01469832) published in Ophthalmology. Focal areas of subretinal hyperpigmentation developed in all participants in a dose-dependent manner in the recipient retina and persisted after withdrawal of systemic immunosuppression. There was no evidence of uncontrolled proliferation or inflammatory responses. Borderline improvements in best-corrected VA in 4 participants either were unsustained or were matched by a similar improvement in the untreated contralateral eye. Microperimetry demonstrated no evidence of benefit at 12 months in the 12 participants. In one instance at the highest dose, localized retinal thinning and reduced sensitivity in the area of hyperpigmentation suggested the potential for harm. Participant-reported quality of life using the 25-item National Eye Institute Visual Function Questionnaire indicated no significant change. Given the slow rate of progressive degeneration at this advanced stage of disease, any protection against further deterioration may be evident only after a more extended period of observation [3].
Feb 15Results of two PI/II studies conducted in the US published in the Lancet. Their aims were to assess the primary endpoints safety and tolerability of subretinal transplantation of hESC-derived retinal pigment epithelium in nine patients with Stargardt´s macular dystrophy (age >18 years) and nine with atrophic age-related macular degeneration (age >55 years). Three dose cohorts (50,000, 100,000, and 150,000 cells) were treated for each eye disorder. Transplanted patients were followed up for a median of 22 months by use of serial systemic, ophthalmic, and imaging examinations (NCT01345006: SMD) and (NCT01344993: AMD). There was no evidence of adverse proliferation, rejection, or serious ocular or systemic safety issues related to the transplanted tissue. Adverse events were associated with vitreoretinal surgery and immunosuppression. 13 (72%) of 18 patients had patches of increasing subretinal pigmentation consistent with transplanted retinal pigment epithelium. Best-corrected visual acuity, monitored as part of the safety protocol, improved in ten eyes, improved or remained the same in seven eyes, and decreased by more than ten letters in one eye, whereas the untreated fellow eyes did not show similar improvements in visual acuity. Vision-related quality-of-life measures increased for general and peripheral vision, and near and distance activities, improving by 8-20 points 3-12 months after transplantation in patients with SMD [4].
Jan 13PI/II 5-year long-term, follow- up study starts (NCT02941991). 11 patients previously transplanted with sequential doses of hESC-RPE cells, starting at a dose of 50,000 hESC-RPE cells and increasing to a maximum dose of 200,000 hESC-RPE cells will be included. Patients will be evaluated at 18, 24, 36, 48 and 60 months post-transplant (or more frequently as clinically indicated). Follow-up will include obtaining information about ophthalmological findings and events of special interest as defined in the Primary Outcome. At the last visit of this follow up study, whether at 60 months post-transplant or at early discontinuation, patients will be invited to participate in a life-long annual health survey, under a separate protocol, to further monitor long-term safety [2].
Nov 11PI/II study to evaluate the safety and tolerability of RPE cellular therapy in patients with SMD, & to evaluate potential efficacy endpoints to be used in future studies RPE cellular therapy starts (NCT01469832). 12 adults will be recruited in the UK [2].