New Medicines

Neuronal ceroid lipofuscinosis (CLN) type 6 (Batten disease) - first-line


New molecular entity
Amicus Therapeutics
Amicus Therapeutics

Development and Regulatory status

Phase II Clinical Trials
Apr 21Amicus announces that manufacturing is on track to initiate next clinical studies in CLN6 using material from the planned commercial process [9].
Feb 21Granted fast track status in US [10].
Sep 20EMA grants Priority Medicines (PRIME) status to scAVV9.CB.CLN6 (AT-GTX-501) for the treatment of neuronal ceroid lipofuscinosis (Batten disease) [4].
Aug 20Amicus reports that regulatory interactions are ongoing and it expects to provide feedback on the path forward in early 2021 [5].
Jan 20Granted orphan drug status and rare pediatric disease status in the US [4].
Aug 19Granted orphan drug status in EU [3].


A self-complementary adeno-associated viral vector (AAV9) carrying the CLN6 gene under the control of a hybrid CMV enhancer/chicken-β-actin promoter
Batten disease is caused by a mutation in the CLN3 gene at gene locus 16p12.1. Of the nine clinical variants (CLN1-CLN9), six have been genetically identified (as well as the CLN3 gene, these include CLN1, CLN2, CLN5, CLN6 and CLN8). It occurs in about 1 to 5 cases per 100,000 generally. There is often rapid deterioration of vision and a slower, but progressive deterioration of intellect. Seizures and psychosis develop later, and there may be features of Parkinson disease [1].
Neuronal ceroid lipofuscinosis (CLN) type 6 (Batten disease) - first-line

Trial or other data

Apr 21PI/II study (AT-GTX-501-01; NCT02725580) continues and is now due to complete collection of primary outcome data in Nov 21. Long term follow up study (AT-GTX-501-02; NCT04273243) is still recruiting [8].
Nov 20PI/II study (AT-GTX-501-01; NCT02725580), which has already finished recruiting from sites in the US, is now due to complete all data collection in Nov 21. The long term follow up study (AT-GTX-501-02; NCT04273243) was recruiting (as of Feb 20) and collection of all data is due to complete Jan 35 [6].
Oct 20Amicus announces positive interim data from the PI/II trial (NCT02725580). Interim safety data are available for 13 children. Interim efficacy data are available for the first 12 children reaching the 12-month timepoint and for eight children up to 24 months, post-administration of the AAV-CLN6 gene therapy. Treatment with AT-GTX-501 was generally well tolerated. The majority of adverse events (AEs) were mild and unrelated to treatment. No pattern of adverse events related to AAV or CLN6 immunogenicity was observed. The Hamburg Motor & Language Score, an assessment of ambulation and speech, shows a meaningful effect in slowing disease progression at 12 and 24 months. On a combined scale of 0 to 6, the mean rate of decline was 0.4 vs 1.2 points over 12 months in treated patients (n=12) vs subjects from the natural history cohort (n=16). On a combined scale of 0 to 6, the mean rate of decline was 0.6 vs 2.4 points over 24 months in treated patients (n=8) vs subjects from the natural history cohort (n=16). Natural History (n=16): Within the natural history cohort, two years from their first decline on the Hamburg Motor & Language Score 63% of subjects experienced an additional 2-point decline (10 out of 16), compared to only 13% of treated patients (1 out of 8) [7].
Oct 19PI/II study (NCT02725580) is active but has finished recruiting [2].
Mar 16PI/II open-label, single-dose study of AT-GTX-501 administered intrathecally into the lumbar spinal cord region of patients with mild to moderate CLN6 Batten disease starts (NCT02725580). This study consists of a one-time injection of AT-GTX-501 with follow-up visits on Day 7, 14, 21, and 30, and every 3 months thereafter, ending at Month 24. The primary outcome for this clinical study is safety evaluated based on the development of dose limiting toxicity (defined as any unanticipated AE that is considered related to AT-GTX-501 and is Common Terminology Criteria for Adverse Events Grade 3 or higher). The secondary outcome measures include the modified Hamburg scale, Unified Batten Disease Rating Scale (UBDRS), brain magnetic resonance imaging (MRI), cognitive and language evaluations, Pediatric Quality of Life™ (PedsQL) inventory, ophthalmologic examinations, and long-term monitoring electroencephalograms. A long-term follow-up safety and efficacy study in subjects with CLN6 Batten disease who received AT-GTX-501 in Study AT-GTX-501-01 is planned (Study AT-GTX-501-02). 13 patients aged 1 year and old (including adults) will be recruited in the US. Collection of primary outcome data is due to complete Oct 21 [2].