Fidanacogene elaparvovec

London: U.S. prices for newly-launched pharmaceuticals more than doubled last year compared to 2021, as companies leveraged scientific advances to develop more therapies for rare diseases, which typically command high prices, a Reuters analysis found. The median annual list price for a new drug was over $370,000 in 2024, according to the Reuters survey of 45 medicines. In 2021, the median price was $180,000 for the 30 drugs first marketed through mid-July, according to a study published in JAMA based on the same criteria. The median launch price was $300,000 in 2023 and $222,000 in 2022. The increase in prices has occurred even as the U.S. government tries to rein in prescription costs. Drug pricing has become a populist issue for President Donald Trump, who has called for drugmakers to bring U.S. prices in line with other high-income nations that pay far less. William Padula, professor of pharmaceutical and health economics at the University of Southern California, said there is no indication that the trend will slow - at least until there is progress in lowering the cost of developing new therapies. "For years we've had pretty good technology and solutions for a lot of the common conditions that many people have, like high cholesterol, high blood pressure, and managing the more common forms of cancer," Padula said. For rare diseases, there are fewer patients "and therefore the price per course of treatment is going to go up," he said. The percentage of drugs launched for orphan diseases, meaning they affect fewer than 200,000 Americans, rose to 72% in 2024 from 51% in 2019, according to the Iqvia Institute for Human Data Science. Over 40% of the orphan launches were for oncology. The other 28% included drugs for larger populations, such as schizophrenia drug Cobenfy, sold by Bristol Myers at a list price of $22,500 a year. The leading industry trade group, the Pharmaceutical Research and Manufacturers of America, said focusing on list prices for drugs that treat rare diseases "misses the broader context of how these drugs contribute to overall prescription drug spending, healthcare costs and value to patients." FOLLOWING THE SCIENCE Decoding of the human genome, completed in 2003, has paved the way for better understanding of the genetic and biological underpinnings of rare diseases, leading to advancements in medical science. Drugmakers are given incentives to invest in research for rare diseases, including longer periods of market exclusivity, in part because potential sales may be limited. Boston Consulting Group projected the 2024 crop of drug launches would reach peak annual sales of $60 billion, significantly lower than past averages due to the absence of mega-blockbusters, a term used to describe drugs with annual sales above $10 billion. The FDA approved 57 novel drugs last year, including seven new cell and gene therapies at the agency's biologic division. In 2023, the agency approved 55 drugs and 17 new biologics. Reuters surveyed the makers of 45 new drugs launched last year. The price analysis excludes imaging agents, vaccines, drugs used intermittently such as antibacterials, and products that have not yet launched commercially. The highest price for a drug taken consistently was over $1 million a year for Zevra Therapeutics' Miplyffa for Niemann-pick disease type C, an inherited metabolic disorder diagnosed in about 900 people in the United States. Orchard Therapeutics' Lenmeldy gene therapy for a rare inherited disorder that affects the brain and nervous system, was launched last year at a record-high price of $4.25 million for a one-time treatment. Pfizer's hemophilia gene therapy Beqvez was priced in 2024 at $3.5 million, but the company pulled it from the market less than a year later citing soft demand. Pharmaceutical companies say new medicines offer cost-saving value, including potentially fewer emergency room visits and hospital stays, and with some treatments using gene editing, the possibility of a cure. Drugmakers also stress they do not determine the portion of drug costs that are born by patients under health insurance plans. Many offer savings cards and other programs to reduce out-of-pocket costs, while insurers can receive discounts and rebates from manufacturer list prices, especially if competing treatments are available. (Reporting By Deena Beasley; Editing by Caroline Humer and Bill Berkrot)

Following a patient death, Neurogene dropped the high-dose arm of the NGN-401 trial, continuing a lower dose 1E15-vg arm with the permission of the FDA.\n After a patient died following a high dose of Neurogene’s Rett syndrome gene therapy candidate, the biotech is sharing details about the event and the new safety protocols being incorporated into the ongoing trial.The young girl had experienced a severe hyperinflammatory condition called hemophagocytic lymphohistiocytosis (HLH) associated with high doses of the adeno-associated virus (AAV) vector therapy, Neurogene said in a presentation set to be shared at 3 p.m. ET on May 16 at the American Society of Gene & Cell Therapy annual meeting in New Orleans.Neurogene first disclosed the adverse event on Nov. 11, 2024. The patient\'s condition had turned critical by Nov. 18. The patient then passed away on Nov. 20. Neurogene detailed the timeline of events for the first time in the May 16 presentation.The patient received 3E15 vector genomes of gene therapy NGN-401 on Nov. 5 as part of the high-dose arm of Neurogene’s ongoing phase 1/2 open-label, pediatric study. She developed a fever before being discharged from the hospital after treatment and was readmitted the next day with a fever, lethargy, vomiting, sleepiness, cough and poor appetite, according to the presentation.Once back in the hospital, doctors treated her with antibiotics, supplemental oxygen, IV fluids and a high dose of steroids. However, her condition declined rapidly and she was admitted to the ICU with respiratory failure, acute kidney injury and extremely low blood pressure.“Despite maximal supportive care,” Neurogene said in the presentation, “multi-system failure was too far advanced.” The patient died from HLH about two weeks after dosing. NGN-401 is designed to use an AAV vector to deliver functional copies of the MECP2 gene to patients with Rett syndrome, a rare genetic disease that emerges within a few years of birth. Most Rett syndrome cases involve mutations in MECP2, with symptoms including slowed growth, trouble with movement, coordination and communication, and intellectual disabilities.HLH is an uncommon but known potential side effect of AAV-based gene therapies and is otherwise a rare inherited condition that typically affects children and young adults. The disease causes a variety of symptoms, including vomiting, breathing difficulties and liver enlargement, and is characterized by “immune dysregulation, cytokine storm and multi-organ damage,” Neurogene said in the presentation.Following the girl’s death, Neurogene dropped the high-dose arm of the NGN-401 trial, continuing with a lower dose 1E15-vg arm with the permission of the FDA.“The company is not aware of any case of HLH ever being reported at this dose level in AAV gene therapy,” Neurogene said in a May 16 release. About 1.3% of serious adverse events in patients receiving high AAV doses show signs of HLH, according to the Neurogene presentation, which cites an FDA analysis of 4,500 Zolgensma treatment cases. The biotech is now incorporating standard HLH monitoring and an HLH treatment algorithm into the trial. The biotech recommends that all AAV gene therapies use doses below 1E14 vg per kilogram and monitor patients for signs of HLH using the three F’s: fever, falling red blood cell counts and raised ferritin levels.Numerous gene therapy outfits have moved away from AAV recently. Earlier this month, Vertex Pharmaceuticals announced it would no longer pursue the viral vectors as a gene therapy delivery tool. Likewise, Takeda announced it was ending early-stage AAV work in 2023.On the approved drug side, Pfizer pulled the AAV-using hemophilia B gene therapy Beqvez from shelves earlier this year, citing limited interest from patients and doctors. No patients seem to have received commercial Beqvez since it was approved by the FDA in April 2024.