| Clinical data | |
|---|---|
| Drug class | gene therapy |
DFT383 is an investigational gene therapy under development by Novartis for the treatment of cystinosis, a rare autosomal recessive lysosomal storage disorder caused by mutations in the CTNS gene, leading to cystine accumulation in cells. [1]
The therapy delivers a functional copy of the CTNS gene via autologous hematopoietic stem cell (HSC) transplantation to address the disease’s root cause, targeting patients both pre- and post-kidney transplant. [2]
DFT383 involves extracting a patient’s hematopoietic stem cells, genetically modifying them ex vivo with a lentiviral vector to insert a functional CTNS gene, and reinfusing them after myeloablation. [3] [4]
The modified cells are intended to produce functional cystinosin, a lysosomal cystine-proton symporter, reducing cystine accumulation throughout the body, including in the kidneys, eyes, and other organs. [5]
In preclinical studies using Ctns−/− mice, treatment with lentiviral-based CTNS gene therapy resulted in significant reductions in tissue cystine levels and preservation of kidney, eye, and thyroid function. [6]
DFT383 was initially developed by AVROBIO as AVR-RD-04, with early clinical trials sponsored by the University of California, San Diego. [7]
A Phase I/II trial, approved by the FDA in November 2018, enrolled six adult patients and showed sustained engraftment, reduced leukocyte cystine levels, and improvements in visual and motor functions up to 36 months post-treatment, with patients discontinuing oral cysteamine. [8] [9] No serious adverse events related to the therapy were reported. [8]
In May 2023, Novartis acquired DFT383 from AVROBIO for $87.5 million, including intellectual property and transition services, to bolster its gene therapy pipeline. [10] [11]
Novartis committed to collaborating with the cystinosis community to advance the program, though timelines from AVROBIO’s initial projections were adjusted during the transition. [12] [13]
As of August 2024, DFT383 is in Phase I and Phase II clinical trials to assess safety and efficacy. [2]
The trial builds on AVROBIO’s Phase I/II data, which demonstrated durable reductions in cystine levels and potential systemic benefits. [8] Novartis is expected to release further results in 2025, though specific trial details remain limited. [14]
DFT383 aims to address limitations of the current standard treatment, cysteamine, which reduces cystine levels but has side effects and does not restore kidney function. [5] Challenges include optimizing trial timelines post-acquisition and ensuring long-term efficacy across diverse patient populations, including children. [15] Future phases may expand eligibility to pediatric patients, pending regulatory approval. [9]