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Submission: On November 13 via api from US — Scanned from DE
Effective URL: https://endpts.com/verve-shares-first-base-editing-results-in-patients-with-hefh/
Submission: On November 13 via api from US — Scanned from DE
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* Channels * All News * In Focus * Special * AI * Bioregnum * Biotech Voices * Cell/Gene Tx * China * Coronavirus * Deals * Diagnostics * Discovery * FDA+ * Financing * Health Tech * Law * Letters to the Editor * Manufacturing * Marketing * Opinion * Outsourcing * Peer Review * People * Pharma * R&D * Startups * Weekly * Webinars * Biopharma Jobs * More * Work at Endpoints * Letter to Editors * IPO Tracker * Webinars * Events * Sponsored Posts * Advertise * Privacy Policy * Endpoints Merch * About Us * Help * SIGN UP * LOG IN November 12, 2023 03:30 PM ESTUpdated 2 hours ago R&D VERVE SHARES FIRST BASE EDITING RESULTS IN HUMANS, SUGGESTING THERAPY CAN LOWER CHOLESTEROL IN PATIENTS WITH GENETIC CONDITION LEI LEI WU NEWS REPORTER PHILADELPHIA — Verve Therapeutics’ next-generation gene editing treatment lowered cholesterol levels in a handful of patients with heterozygous familial hypercholesterolemia, marking the first time that base editing has been used to directly alter DNA in humans. The early Phase I data, presented Sunday at the American Heart Association’s scientific meeting, give a glimpse at how the in vivo treatment works in people who have been diagnosed with the genetic disorder that causes high cholesterol and often heart disease at an early age. One patient who received the highest dose (0.6 mg/kg) saw a 55% reduction in their cholesterol levels from baseline after one month, with levels staying low six months after the patient received the infusion of the gene editing treatment. Two other patients who received a slightly lower dose (0.45 mg/kg) saw 48% and 39% reductions in their cholesterol levels after one month. advertisement advertisement Karol Watson “This is a strategy that could be revolutionary, but we have to make sure it’s safe,” Karol Watson, a cardiologist at the David Geffen School of Medicine at UCLA, said at a press briefing ahead of the presentation. Watson was not involved in the study. The goal of Verve’s treatment, known as VERVE-101, is to use base editing in the liver to permanently turn off PCSK9, a gene that encodes a protein that is central to regulating the amount of cholesterol in the blood. Unlike CRISPR/Cas9, base editing doesn’t need to cut both strands of DNA. Instead, it makes a chemical change on a single letter in the DNA code to inactivate the gene. Verve said Sunday that in human liver cells treated with VERVE-101, it found no evidence of off-target editing in over 6,000 candidate sites. While the data from the heart-1 study are very early, the cholesterol-lowering result is in line with already approved PCSK9 medicines. In clinical trials, Leqvio — an RNA therapy from Novartis — lowered cholesterol levels by around 40% in patients with HeFH. Leqvio, which won FDA approval at the end of 2021, is dosed every three to six months. Other approved cholesterol-lowering medicines that inhibit PCSK9 — like Amgen’s Repatha and Sanofi and Regeneron’s Praluent — are dosed monthly. All in all, the study enrolled 10 patients. But six patients who received the lowest doses of the therapy (0.1 and 0.3 mg/kg) did not see significant differences in their cholesterol levels after six months. Verve’s stock $VERV dropped more than 30% in premarket trading on Monday. SAFETY QUESTIONS REMAIN One patient in the study died from cardiac arrest five weeks after receiving treatment. Clinicians on the trial said the patient’s death was not related to treatment. Another patient had a heart attack the day after receiving the infusion, which investigators and an independent review board said was potentially related to treatment. Verve said that determination was made based on how close the heart attack happened to dosing, and it also noted the patient had unreported chest pains prior to receiving the infusion. Four weeks after treatment, that patient experienced a brief episode of irregular heart rhythm. Sek Kathiresan Patients who received the two higher doses of the gene editing treatment also experienced fever-like symptoms immediately after their infusions, Verve CEO and co-founder Sek Kathiresan said in an interview with Endpoints News ahead of Sunday’s presentation. Verve’s treatment delivers mRNA packaged in fatty acid bubbles, which can lead to similar side effects experienced by those who received the mRNA Covid-19 vaccines. In addition, patients also saw an increase in liver enzyme levels, which were more elevated in those who received the higher doses. But Verve said that these elevations were transient and did not result in liver damage. Moving forward, Verve intends to enroll patients with more moderate disease at the higher doses, Kathiresan said. He pointed to FDA guidance released last year that suggests early gene editing studies should start with very sick patients. However, the guidance acknowledges that figuring out what safety signals come from the drug and which ones occur as a result of underlying disease can be challenging, and in some cases, enrolling less sick patients could be appropriate. This could be done potentially at sites in the US, where Verve announced last week that it received FDA clearance to run a clinical trial. A year ago, the company had received a clinical hold from the FDA for its base editing treatment, with the agency saying it wanted more preclinical data on the risks of editing germline cells and other non-liver cells before the company started human studies. THE PRICING QUESTION “When people think about one-time therapies, they are thinking millions of dollars for that single dose,” Kathiresan said. “That’s not us, because we’re trying to reach millions of patients.” Currently, the most expensive medicine in the US is CSL Behring and uniQure’s one-time gene therapy for hemophilia B at $3.5 million per patient. Verve’s current trial is for patients with HeFH, which affects around 1 in 300 people around the world, but the company has aspirations to expand to far broader indications like atherosclerosis. It’s still in the early stages of development. “Our drug looks like a Covid vaccine,” he continued. “They’re giving 100 micrograms. You can make that for like $3. We give 50 milligrams, but even if you multiply up, that’s basically low thousands in cost, ultimately at scale.” “For us, it’s going to be less of the gene therapy pricing, but more in line with other one-time cardiovascular procedures — think about bypass surgery, open heart surgery,” Kathiresan said. Repatha and Praluent, in comparison, both cost less than $6,000 a year, far less than any gene therapy on the market. The Cambridge, MA-based company also has a second base editing candidate targeting PCSK9 that uses a different lipid nanoparticle delivery system, which includes an added targeting ligand. The goal is to get into liver cells more efficiently, which Kathiresan hopes can result in the same efficacy but potentially by using a lower dose. Verve plans to start a Phase I clinical trial of that treatment, VERVE-102, in HeFH patients in the first half of next year, Kathiresan said. Once both Phase I studies are completed, Verve expects to pick one candidate to move into Phase II in 2025. Eli Lilly last month purchased opt-in rights to Verve’s programs from Beam Therapeutics, which developed the underlying base editing technology. AUTHOR LEI LEI WU NEWS REPORTER lwu@endpointsnews.com @leilei_wuu TRENDING NOW AFTER SHOWING WEGOVY CUT CARDIOVASCULAR RISK BY 20%, RESULTS DETAIL IMPACT ON DEATH AND HEART FAILURE FIRST DATA FOR LILLY'S RNA TREATMENT FOR HEART DISEASE POINT TO LONG-TERM DURABILITY IN TINY GROUP OF PATIENTS ALNYLAM’S LONGER-TERM RNAI TREATMENT LOWERS BLOOD PRESSURE IN MID-STAGE STUDY ASTRAZENECA PREPARES TO LIVE WITH THE IRA, SHIFTING FOCUS OF ARGUMENTS TO ORPHAN DRUG CHANGES ANTHOS' BLOOD THINNER CUTS THE RISK OF BLEEDING AMID RACE TO DEVELOP SAFER ANTICOAGULANTS sponsored CLINICAL STUDIES IN JAPAN TODAY: ANOTHER LOOK AT THE WORLD’S SECOND-LARGEST PRESCRIPTION DRUG MARKET IN A ... 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