Antisense Therapeutics Limited: Clinical Trial Application submitted for ATL1102 Phase IIb DMD trial conduct in Europe
19 December 2022 - Antisense Therapeutics Limited [ASX:ANP | US OTC:ATHJY | FSE:AWY] (ANP or Company) today announced that it has now submitted a Clinical Trial Application (CTA) in three European countries (UK, Bulgaria and Turkey) for approval to conduct its double-blind, placebo controlled Phase IIb trial of ATL1102 in non-ambulant boys with Duchenne muscular dystrophy (DMD). The CTA submission for Ethics Committee (EC) approval to initiate trial sites in Australia is scheduled for submission following the holiday period to the EC for review early in the new year.
The Phase IIb study aims to enrol and randomize 45 non-ambulant boys with DMD from multiple clinical trial sites in Europe and Australia. Following the initial six-month regimen of either placebo, 25 mg or 50 mg once weekly (blinded phase), participants will continue into a further six-month open label treatment period.
The CTA submissions are a critical step in the clinical trial set-up process and represent the Company’s resolve to develop ATL1102 for DMD. CTA approvals are expected to come through in a staggered manner in early 2023 depending on the respective regulatory agencies’ evaluation process and timelines. As per previous guidance, reporting of the results from the blinded phase of the trial is anticipated in 1H’24.
This announcement has been authorised for release by the Board.
For more information please contact:
Antisense Therapeutics
Mark Diamond
Managing Director
+61 (0)3 9827 8999
Investment Enquiries
Gennadi Koutchin
XEC Partners
1300 932 037
US/European IR & Media
Laine Yonker/Joe Green
Edison Investor Relations
+1 646-653-7035
About Antisense Therapeutics Limited [ASX: ANP | US OTC: ATHJY | FSE: AWY] is an Australian publicly listed biotechnology company, developing and commercializing antisense pharmaceuticals for large unmet markets in rare diseases. The products are in-licensed from Ionis Pharmaceuticals Inc. (NASDAQ: IONS), an established leader in antisense drug development. The Company is developing ATL1102, an antisense inhibitor of the CD49d receptor, for Duchenne muscular dystrophy (DMD) patients and recently reported highly promising Phase II trial results. ATL1102 has also successfully completed a Phase II efficacy and safety trial, significantly reducing the number of brain lesions in patients with relapsing-remitting multiple sclerosis (RRMS). The Company has a second drug, ATL1103 designed to block GHr production that successfully reduced blood IGF-I levels in Phase II clinical trials in patients with the growth disorder acromegaly.
About ATL1102 ATL1102 is an antisense inhibitor of CD49d, a subunit of VLA-4 (Very Late Antigen-4). Antisense inhibition of VLA-4 expression has demonstrated activity in a number of animal models of inflammatory disease including asthma and MS with the MS animal data having been published in a peer reviewed scientific journal. ATL1102 was shown to be highly effective in reducing MS lesions in a Phase IIa clinical trial in patients with RR-MS. The ATL1102 Phase IIa clinical data has been published in the medical Journal Neurology (Limmroth, V. et al Neurology, 2014; 83(20): 1780-1788). ATL1102 is the only drug targeting CD49d in clinical development for DMD.
About DMD Duchenne Muscular Dystrophy (DMD) is an X-linked disease that affects 1 in 3600 to 6000 live male births (Bushby et al, 2010). DMD occurs as a result of mutations in the dystrophin gene which causes a substantial reduction in or absence of the dystrophin protein. Children with DMD have dystrophin deficient muscles and are susceptible to contraction induced injury to muscle that triggers the immune system which exacerbates muscle damage as summarized in a publication co-authored by the Director of the FDA CDER (Rosenberg et al, 2015). Ongoing deterioration in muscle strength affects lower limbs leading to impaired mobility, and also affects upper limbs, leading to further loss of function and self-care ability. The need for wheelchair use can occur in early teenage years for patients on corticosteroids with a mean age of 13, with respiratory, cardiac, cognitive dysfunction also emerging. Patients with a greater number of immune T cells expressing high levels of CD49d have more severe and progressive disease and are non-ambulant by the age of 10 despite being on corticosteroid treatment (Pinto Mariz et al, 2015). With no intervention, the mean age of life is approximately 19 years and with current treatment typically limited to only the second or third decade of life. The management of the inflammatory damage to muscle associated with DMD is currently addressed via the use of corticosteroids prednisolone and deflazacort which delay disease progression prolonging ambulation by a median 2 to 3 years (Shieh et al, 2018) and reduce loss of upper limb function as measured by performance of upper limb function (PUL) scores, (Pane et al, 2018), an objective measurement of function. Corticosteroids are, however, acknowledged as providing insufficient efficacy and are associated with significant side effects including bone loss that require monitoring, management, and treatment (Ward et al 2018). As a consequence, there is an acknowledged high need for new therapeutic approaches for the treatment of the immune mediated inflammation associated muscle damage in DMD.
Rosenberg AS, Puig M, Nagaraju K, et al. Immune-mediated pathology in Duchenne muscular dystrophy. Sci Transl Med 2015, 7: 299rv4.
Bushby et al for the DMD Care Consideration Working Group/ Diagnosis and management of Duchenne muscular dystrophy, part 1 Lancet Neurol. 2010 Jan;9(1):77-93 and part 2 Lancet Neurol. 2010 Feb;9(2):177-89 .
Pinto-Mariz F, Carvalho LR, Araújo AQC, et al. CD49d is a disease progression biomarker and a potential target for immunotherapy in Duchenne muscular dystrophy. Skeletal Muscle 2015, 5: 45-55.
Shieh et al, Deflazacort versus prednisone/prednisolone for maintaining motor function and delaying loss of ambulation: A post HOC analysis from the ACT DMD trial. Muscle Nerve. 2018 Nov; 58(5): 639–645. Muscle & Nerve November 2018 639
Pane M, Coratti G, Brogna C, Mazzone ES, Mayhew A, Fanelli L, Mercuri E et al. (2018) Upper limb function in Duchenne muscular dystrophy: 24 month longitudinal data. PLoS ONE 13(6): e0199223. https://doi.org/10.1371/journal. pone.0199223
Ward L.M, Hadjiyannakis, S, McMillan, HJ, Noritz, G, and Weber, DR, Bone Health and Osteoporosis Management of the Patient With Duchenne Muscular Dystrophy. Pediatrics. 2018 October; 142(Suppl 2): S34–S42. doi:10.1542/peds.2018-0333E.
