A gene therapy has for the first time reduced the level of LDL cholesterol in people with familial hypercholesterolemia, according to preliminary results of a clinical trial presented on Sunday at a meeting of the American Heart Association in Philadelphia (USA).
The treatment consists of inactivating the gene that produces the PCSK9 enzyme in the liver. This enzyme promotes a high level of LDL cholesterol.
An RNA drug to reduce cholesterol that arrived in Spain this month, inclisiran, also acts by inhibiting the PCSK9 enzyme. Likewise, there are antibodies against PCSK9 approved in Europe since 2015.
The advantage of gene therapy over current treatments is that it may be administered only once for its effectiveness to be maintained in the long term, and possibly for life. But first it must be demonstrated that it is effective and safe in clinical trials.
The first is being carried out in people with familial hypercholesterolemia with diagnosed cardiovascular disease in whom the usual treatment is not enough. It is a phase 1 clinical trial started in July 2022 in which different doses will be tested in 44 patients to determine which is the most appropriate.
The results of the first ten patients presented by Verve Therapeutics, which developed the treatment, have been positive, according to the company. In the three patients who received the highest doses, the level of LDL cholesterol was reduced by between 39% and 55% without significant adverse effects.
The treatment is based on lipid nanospheres that are administered by intravenous injection. When they reach the liver, they modify the PCSK9 enzyme gene with a technology called gene base editing. The Boston-based company Verve Therapeutics compares it to an eraser and a pencil. As explained on its website, base editing consists of deleting a letter from the genome and writing another in its place, thus modifying the protein that is produced. In the case of PCSK9, the correction is sufficient to inactivate the enzyme.
The safety of the treatment has not been established. Two of the first ten people treated have suffered cardiovascular accidents, one the day after receiving the injection and the other, who died, five weeks later. According to Verve Therapeutics, these episodes are not a consequence of the treatment but are attributed to the fact that they were high-risk patients.
Valuing the potential of this new technology, the multinational Eli Lilly has paid 60 million dollars to Verve Therapeutics to collaborate in the development of gene therapy and will contribute 250 million more depending on the results obtained.
“Until now we thought of gene editing as a treatment reserved for very rare diseases. But if we can make gene editing safe and available on a large scale, why not address a more common disease?” Daniel Skovronsky, chief scientific and medical officer at Ely Lilly, told The New York Times.
“Of the more than three million people who have familial hypercholesterolemia in the United States and Europe, very few are at the desired level of LDL cholesterol,” said Deepak Bhatt, director of Mount Sinai Fuster Heart Hospital in New York, in a statement. released by Verve Therapeutics. “I am very encouraged by the initial clinical trial data demonstrating the potential of single-dose gene editing as a new strategy to treat patients with familial hypercholesterolemia.”
The clinical trial currently underway should conclude at the end of 2024. As reported by Verve Therapeutics, a phase 2 trial is planned to begin in 2025 with a larger sample of patients.