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DMD Cell Therapy Shows Promise in Early Clinical Trial Data

The 3 patients demonstrated a mean significant improvement of up to 200% of baseline in motor unit potential.

Dystrogen Therapeutics’ DT-DEC01, an investigational chimeric cell therapy intended for the treatment of Duchenne muscular dystrophy (DMD), has demonstrated promising safety and efficacy in 6-month data from 3 patients treated in an on-going clinical trial in Poland.1

The 3 patients demonstrated a mean significant improvement of up to 200% of baseline in motor unit potential (MUP). Furthermore, because all 3 patients had different genetic mutations in the DMD gene, the results indicate that DT-DEC01 could be a universal therapy for patients with DMD. In terms of safety, no adverse events associated with DT-DEC01 were reported.

"There are currently no approved treatments for boys and young men with DMD that result in a cure or significant attenuation of the disease,” Kris Siemionow, MD, PhD, chief executive officer, Dystrogen Therapeutics, said in a statement regarding the news.1 “It is very encouraging that we continue to see consistent positive clinical and biomarker data from our investigational DT-DEC01 engineered cell therapy, even at this low dose, and that the benefit of the therapy is sustained at 6 months.”

DT-DEC01 is an engineered cell product and is meant to engraft in skeletal and cardiac muscle. It is intended to deliver a functional copy of DMD and related components necessary for healthy functioning of muscle cells. It was designed with the intention of not requiring immunosuppression, and thus far no evidence of immune reactions to the therapy in 6-month blood assays has been reported in the patients treated.

All 3 patients included in the data were in the trial’s low-dose cohort (2 million dystrophin expressing chimeric cells per kg).1,2 The 3 patients include a 7-year-old patient who is ambulatory and has a deletion in exon 3-12 (patient 1), a 15-year-old patient who is non-ambulatory and has a deletion in exon 48-50 (patient 2), and a 6-year-old patient who is ambulatory and has a nonsense mutation (patient 3). These 3 patients achieved up to 108%, 287%, and 124% of pretreatment baseline improvement in duration and amplitude of MUPs on EMG (biomarker), respectively.

Patient 1 additionally showed an improvement from 430m to 469m on the 6-minute walk test (6MWD) and from 31 to 34 on the North Star Ambulatory Assessment (NSAA) total score, and also improved by 14% on 10-meter walk/run time and improved by more than 1.6 kg on grip strength. Patient 2 showed an improvement of more than 1.7 kg on grip strength. Patient 3 improved from 339m to 390m on the 6MWD, improved from 26 to 28 on NSAA total score, and showed improvement on the supine to stand test (5%). According to the activity tracker, patients 1 and 3 both showed statistically significant increases in step count, while patient 2 showed a statistically significant increase in activity. Additionally, patients 1 and 3 showed improvements in Pediatric Outcomes Data Collection Instrument score, and patients 2 and 3 showed improvements in Performance of Upper Limb score.

“The improvements in functional and biomarker measures at 6 months in participants from the low dose cohorts who received DT-DEC01 are distinctly different from what an age-matched, natural history group would predict with DMD,” Siemionow added to the statement.1 “When coupled with strong and sustained dystrophin expression in preclinical studies and encouraging clinical safety profile at 6 months, today's results increase our confidence in DT-DEC01 and provide additional supportive evidence for this approach."

DT-DEC01 previously was granted orphan drug designation and rare pediatric disease designation by the FDA in August 2020.3 In April 2022, Dystrogen Therapeutics provided a 3-month update on the low-dose cohort, and at that time the Data and Safety Monitoring Board (DSMB) offered a positive opinion on the therapy’s safety and recommended the initiation of the 4 million cells/kg cohort.2

REFERENCES
1. Dystrogen Therapeutics investigational chimeric cell therapy DT-DEC01 for Duchenne muscular dystrophy demonstrates clinically significant functional and biomarker improvements. News release. Dystrogen Therapeutics, Corp. September 26, 2022. https://www.prnewswire.com/news-releases/dystrogen-therapeutics-investigational-chimeric-cell-therapy-dt-dec01-for-duchenne-muscular-dystrophy-demonstrates-clinically-significant-functional-and-biomarker-improvements-301633161.html 
2. Dystrogen Therapeutics investigational chimeric cell therapy DT-DEC01 for the treatment of Duchene muscular dystrophy shows safety and functional improvements. News release. Dystrogen Therapeutics, Corp. April 7, 2022. https://www.prnewswire.com/news-releases/dystrogen-therapeutics-investigational-chimeric-cell-therapy-dt-dec01-for-the-treatment-of-duchene-muscular-dystrophy-shows-safety-and-functional-improvements-301520140.html 
3. FDA has granted Dystrogen Therapeutics Rare Pediatric Disease (RPD) Designation and Orphan Drug Designation for the company’s product candidate: Dystrophin Expressing Chimeric (DEC) Cell Therapy DT-DEC01. News release. Dystrogen Therapeutics, Corp. August 18, 2020. http://dystrogen.com/wp-content/uploads/2021/11/Press-release-FDA-August18-2020-2.pdf