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CRISPR Therapeutics has revealed promising but early data from its first clinical study of a gene editing therapy to lower the risk of heart disease, setting the stage for competition with other drugmakers working on similar treatments. The therapy, dubbed CTX310, uses lipid nanoparticles (LNPs) to deliver the CRISPR therapy into the liver, where it cuts a gene called ANGPTL3. The approach aims to mimic the effects of natural mutations that cause some people to have unusually low levels of cholesterol and triglycerides. The Phase 1 trial tested four dose levels in 10 people, but the most dramatic results came from the sole patient who got the highest dose, which reduced their triglyceride levels by 82% and low-density lipoprotein (LDL) — often called “bad” cholesterol — by 65% a month after the infusion. Three patients who got the second-highest dose had their triglycerides reduced by an average of 56% and their LDL cholesterol by an average of 29%, although one of those patients had an 81% reduction. The six people who got the smallest two doses had only minor triglyceride reduction. The topline results were announced Tuesday afternoon in a press release . It was the first time that CRISPR Therapeutics shared results from a study testing its namesake technology as an infusion directly into the body. “We’re seeing dramatic reductions in triglycerides,” CRISPR Therapeutics CEO Samarth Kulkarni told Endpoints News in an interview. “Gene editing works.” Much larger studies will be needed to prove the safety and efficacy of the drug, but the preliminary results build on positive data from Beam Therapeutics, Intellia Therapeutics and Verve Therapeutics, which have also successfully used lipid nanoparticles to deliver gene editing therapies to the liver. “Once we establish an LNP platform for the liver, we can keep adding targets and developing more drugs in a derisked fashion,” Kulkarni said. “And the mRNA we make is applicable to all the programs, so our costs are going to go down over time, too.” CRISPR Therapeutics hopes that its treatment may one day lower the risk of heart disease in many people. But first, it is testing the drug in patients with severe conditions, including familial hypercholesterolemia, severe hypertriglyceridemia and mixed dyslipidemias. The company said the two highest doses of its therapy reduced ANGPTL3 by up to 75%, but didn’t say what the average reduction was. There were no severe adverse reactions to the drug. And there were no meaningful changes to liver enzyme levels or platelets, two potential problems caused by some gene therapies. CRISPR’s triglyceride reduction appears roughly on par with the 52% lowering seen in a Phase 2 study of solbinsiran, an siRNA drug made by Eli Lilly that also targets ANGPTL3. But CRISPR Therapeutics is quick to note its potential edge in LDL cholesterol, which Lilly’s drug only reduced by about 12% to 17%. “The LDL reduction seems to be a lot higher than some of the siRNA therapies. So this could end up being a best-in-class therapy,” Kulkarni said. “So from that perspective, we’re absolutely thrilled.” Regeneron already sells an antibody drug called Evkeeza that also targets ANGPTL3. In a study of people with familial hypercholesterolemia, the drug reduced LDL cholesterol by 49% and triglycerides by 50%. By targeting a different gene called PCSK9, Verve has reduced LDL cholesterol levels by about 53% in a recent study . The company also began a clinical trial of a therapy that targets ANGPTL3 last year, and it expects to share updates in the second half of 2025. CRISPR Therapeutics expects to present more details at a medical conference in the second half of 2025. The company is also planning to share data from a Phase 1 study of a similar therapy that aims to reduce lipoprotein(a), another lipid linked to heart disease, in the second quarter this year. On Tuesday, the company also shared an update on the commercial launch of Casgevy, its CRISPR-edited cell therapy for sickle cell disease and beta thalassemia. More than 90 patients have had their bone marrow stem cells collected to begin the process of making the therapy, and the company expects that number will “grow significantly” this year, the company said in its press release. Kulkarni told Endpoints that eight patients received Casgevy in the first quarter of 2025, a notable uptick from previous quarters but still a far cry from the roughly 300 patients the company needs to treat each year to break even on the therapy, according to one analyst . CRISPR’s stock fell more than 11% on Tuesday, coinciding with the appointment of controversial scientist Vinay Prasad as the new director of the Center for Biologics Evaluation and Research, the division of the FDA responsible for regulating gene editing. Kulkarni wouldn’t comment on the potential impact on CRISPR Therapeutics, but he did say that other recent shakeups at the agency haven’t affected the company yet. “There are a lot of people who are worried about how the FDA is functioning, and so far, for us, we’ve had interactions where it’s been business as usual. So we have not, at the ground level, felt any disruptions,” Kulkarni said. Editor’s note: A previous version of this story incorrectly said that Verve had not begun testing its ANGPTL3 therapy. The drug is in a clinical trial.

iStock, ArtemisDiana CRISPR Therapeutics’ partner Vertex reported that more than 65 treatment centers have been activated for the gene therapy Casgevy. While Vertex handles the market, CRISPR has been focused on its clinical program. The outlook for CRISPR Therapeutics’ approved gene therapy Casgevy is starting to look up, with more treatment centers added over the past quarter. The positive trend comes just as the gene editing biotech reported that its cholesterol-lowering gene therapy dropped lipoprotein and triglycerides in a Phase I trial, showcasing the potential of gene therapy if the space can overcome its commercial hurdles . CRISPR’s partner Vertex reported earlier this week that more than 65 treatment centers have been activated for Casgevy, which is approved for sickle cell disease and beta-thalassemia . The revelation provided a glimmer of hope for the gene therapy space, which has been battered by bad news. Vertex reported revenue of $14.2 million for Casgevy in the first quarter, up a modest but encouraging 4%, according to William Blair analysts. This growth signals that “the ramp in patient starts is beginning to convert to a ramp in cell infusions,” the group wrote in a note to investors Wednesday morning. In September 2024, patients finally started to receive infusions of Casgevy, 10 months after its December 2023 approval. It’s been a slow build for a modality that could have profound impacts on the lives of patients. The treatments have struggled to gain market share; they are expensive and challenging for patients to undergo. The companies involved have also had to build out a network of treatment centers capable of supporting patients through the process. As CRISPR and Vertex have charged ahead, rival bluebird bio has fallen behind. Once a promising gene therapy company, bluebird sold itself to private equity earlier this year for a mere $30 million after failing to reach profitability in time to make up a looming cash gap . But CRISPR has the backing of a much larger pharma company in Vertex, which has been leading the marketing efforts. Vertex has set a goal of activating 75 treatment centers globally, and has hit 65 already, Chief Operating Officer Stuart Arbuckle explained on Vertex’s first quarter earnings report Monday. “Casgevy truly does have the potential to be a multibillion-dollar product for Vertex,” Arbuckle said. About 90 patients have undergone the initial cell collection process, according to Arbuckle, and more than twice that number have been referred to begin treatment. A total of eight patients have completed treatment. “It’s been inspiring to hear that Casgevy patients now feel able to live their lives in ways they never have before,” Arbuckle said. “Whether that means having the energy to play with their kids, taking up snowboarding without fear that the cold might bring on a pain crisis or investing in their education and careers given expectations now for a longer and healthier life. It is a privilege to be part of their journey.” Laser-Focused While Vertex handles the market, CRISPR has been cleared to focus on its clinical program, such as the in vivo liver editing program CTX310. On Tuesday, the company reported a small batch of data from just 10 patients with elevated lipoprotein (LDL) and triglyceride (TG) levels in a first-in-human trial of the gene therapy. A single dose of the treatment decreased expression of the ANGPTL3 gene, which is involved in the regulation of LDL and TG levels. Both LDL and TG decreased as well. One patient with severe hypertriglyceridemia had an 82% reduction in TG. Another with heterozygous familial hypercholesterolemia had an 81% reduction in LDL-C, a measure of the cholesterol carried by LDL particles. William Blair said the data “looks competitive” with LDL-C reductions seen with Arrowhead Therapeutics ARO-ANG3 and Regeneron’s approved therapy Evkeeza. CTX310 was well tolerated and there were no severe adverse events reported. CRISPR also noted that liver enzymes were not elevated at any dose level. CRISPR heralded the results as a “significant milestone” for its proprietary lipid nanoparticle (LNP) delivery technology for gene editing in the liver. More data from the Phase I trial will be presented at a medical meeting later this year. CRISPR is also developing CTX320 for cardiovascular disease, with a Phase I readout expected in the second quarter. “We also think the safety pro CTX310 de-risks the upcoming readout from CTX320, and we highlight that CRISPR is the only company with an in vivo gene-editing candidate targeting Lp(a) in the clinic,” William Blair said. The company is also working on two preclinical programs, CTX340 for refractory hypertension and CTX450 for acute hepatic porphyrias. In oncology, CRISPR will have a readout for a Phase I trial of CTX131 in solid tumors and blood cancers sometime this year. An update for the regenerative medicine diabetes treatment CTX211 is also expected before the end of 2025. “We view CRISPR as having a catalyst-rich 12-month period ahead as it advances candidates across its ex vivo and in vivo platforms through the clinic,” William Blair wrote.