April 1, 2019

This article discusses diseases targeted in AAV gene therapy clinical trials initiated since 2003 through January 2019. It includes interventional, long-term follow up, and some observational studies. The review also covers industry sponsor involvement, volume of trials in each disease, and most advanced clinical development achieved in each indication to date.

As of January 2019, over 200 clinical trials have been initiated in AAV gene therapy.

These trials cover approximately 53 diseases. The bar graph (Figure 1) shows the number of initiated trials in each of the 53 diseases, grouped by therapeutic area (TA). (Main source: clinicaltrials.gov, downloaded on Jan 31, 2019). You can view disease names by hovering over each bar. Hemophilia B is the leading indication in terms of the number of initiated clinical trials to date. Neurology and ophthalmology are leading TAs with respect to diversity of targeted conditions.

Industry sponsors in AAV gene therapy clinical trials

AAV gene therapy trials have been initiated by both industry and non-industry sponsors. Here, we are highlighting any level of industry involvement, i.e., past or present, main sponsor or co-sponsor. Table 1 summarizes the results. Some industry sponsors no longer exist, either due to M&A activity or dissolution. Indications that have generated the greatest industry interest include hemophilia, DMD, Parkinson’s, and LCA.

No industry involvement in clinical trials does not mean that companies do not conduct or sponsor preclinical studies. Companies have announced preclinical development in CLN2, LGMD2C (marked with*), and other diseases. We are planning to publish a full preclinical program analysis on our website soon. Please subscribe to receive a notification.

AAV gene therapy clinical development progress

Next, we looked at the most advanced trials for each disease to gauge clinical development success. Table 2 summarizes the results. Green cells highlight late-stage programs, i.e., Phase 2/3 through approval. As of January 2019, AAV gene therapies in late stage clinical development have targeted LPL deficiency, LCA, hemophilia, SMA, LHON, choroideremia, and MPS3A. AAV gene therapy clinical trial progress has been especially slow in arthritis, HIV, Pompe, Alzheimer’s, CLN2, LGMD2C, A1AT deficiency, and cystic fibrosis (CF) (highlighted in red). However, these diseases gained a lot of attention at the ASGCT 2019 annual meeting (see our report here.) The interest in finding cell and gene therapy solutions for these disorders is certainly strong.

Finally, we looked at the most recently initiated trials for each disease, through January 2019, to gauge the level of interest in pursuing specific indications. Table 3 summarizes the results. In red are trials that have been initiated over eight years ago: CLN2, LGMD2C, and cystic fibrosis (CF). However, preclinical progress in these conditions reported to date (ASGCT 2019 and various press releases) indicates that clinical development will likely continue in the near future. Of these three conditions, cystic fibrosis has already been targeted by variety of non-AAV gene therapy approaches, including mRNA (NCT03375047) and antisense oligonucleotides (NCT02564354, NCT02532764, NCT03647228).

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Abbreviations

A1AT = alpha-1 antitrypsin;
AADC = aromatic amino acid decarboxylase;
AIP = acute intermittent porphyria;
BMD = Becker muscular dystrophy;
CF = cystic fibrosis;
CHF = congestive heart failure;
CLN = neuronal ceroid lipofuscinosis;
CMT1A = Charcot-Marie-Tooth neuropathy type 1A;
dAMD = dry AMD;
DMD = Duchenne muscular dystrophy;
GAN = giant axonal neuropathy;
GSD = glycogen storage disease;
HF = heart failure;
HoFH = homozygous familial hypercholesterolemia;
LGMD = limb-girdle muscular dystrophy;
LHON = Leber hereditary optic neuropathy;
LPL = lipoprotein lipase;
MLD = metachromatic leukodystrophy;
MPS = mucopolysaccharidosis;
nAMD = neovascular (wet) age related macular degeneration;
OTC = ornithine transcarbamylase;
RP = retinitis pigmentosa;
sIBM = sporadic inclusion body myositis;
SMA = spinal muscular degeneration;
XLRP = X-linked retinitis pigmentosa;
XLRS = X-linked retinoschisis.
LTFU = long-term follow up
Disclaimer: This article is based on publicly available information ONLY. The information is sourced from clinicaltrials.gov, 10k filings, company websites, press releases, and peer review publications. This article is not a legal advice. Information in this article is simply the author’s opinion and insight derived from publicly available information.