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This BioPhorum report came out in April 2023 and is an excellent overview of the challenges in Cell and Gene Therapy supply chain management, the array of solutions and the consequent need for standardisation to the extent possible, not least to reduce the systems-burden on the healthcare professionals. ICCBBA #isbt128

A #Guide To accelarated #Cell and #gene therapy (#CGT) #Commercialization Propelled by several landmark approvals and a robust pipeline, the cell and gene therapy (#CGT) sector is entering a new era – with new #modalities reaching the market and an influx of new therapies, including those that target larger patient populations on the horizon. In the #unitedstates States, there will be regulatory decisions on about 10 #CGT products by the end of this year. And with more than 2,000 #clinicaltrials underway globally, that figure is poised to grow in the next five to 10 years, offering tremendous #promise for patients #worldwide.

Attn: Cell and Gene Therapy Manufacturing professionals! 🧪🧫 Discover the latest insights on "Challenges and Best Practices for Viral Clearance in CGT Products" in this must-read article! 🦠 In this industry, ensuring viral clearance is paramount. But it's not without its hurdles, including questions about study replication, establishing burden, and risk assessments. 🤔 But wait, there's good news! 🌟 This article from @Biophorum offers a game-changing proposal for tackling these challenges head-on. Offerings on best practices aim to make a difference in the world of viral clearance for CGT products. #CellAndGeneTherapy #ManufacturingExcellence #BioPhorum https://bit.ly/45A1iHA

Gene&Cell Therapy >> #JPM24: Ultragenyx nears $50M Series A for its Alzheimer's gene therapy spinout: SAN FRANCISCO — Ultragenyx, the commercial-stage California biotech working on ultra-rare diseases, is finishing up a $50 million Series A fundraise for its Alzheimer’s gene therapy spinout, named Amlogenyx, CEO Emil Kakkis told Endpoints News. “We have a lead investor signed on, and we have several investors who are on board. We’re still trying to fill out a $50 million syndicate,” Kakkis said on the sidelines of this year’s JP Morgan Healthcare Conference on Monday. “We have most of it, or a good part of it, so we’re trying to get the last two, three people to finish it.” At the time of the spinout unveiling last fall, Ultragenyx said it’d seek to have the Series A wrapped up by the end of 2023, but December is a hard month to close financings, Kakkis noted. The biotech will retain a majority ownership of Amlogenyx, he added. “We’re hoping this quarter will be fresh, people will be back in the saddle, we can get deals like this,” Kakkis said. “They’re high risk and high return, and my hope is that the mood in the market will have changed in tone.” Like multiple players in the Alzheimer’s field, Ultragenyx is seeking to go after amyloid beta, a protein thought to lead to the memory-robbing disease when it accumulates in the brain. Eisai and Biogen marked a turning point with their Leqembi approval last year, and Eli Lilly is looking to catch up with its own approval of donanemab this year after a delay to the original PDUFA of late 2023. Many other drugmakers have been burned in the past on amyloid. Amlogenyx thinks a gene therapy approach could have better efficacy than the monoclonal antibodies, with its ability to cleave more of the unhealthy protein. The work is still preclinical but has been continuing to progress since Ultragenyx first announced the spinout plans, Kakkis said, noting about eight people from the company’s early development group would manage Amlogenyx for the first few years, and then a CEO and senior leadership would be appointed to lead it once ready for human trials. Ultragenyx is known for its ultra-rare medicines, having secured multiple approvals since its founding in 2010, and Kakkis has been vocal about increasing accelerated approvals for treatments in the field, as well as getting more biomarker-driven approaches and educating the FDA about the ultra-rare community’s needs. “I tell people this is the golden age for rare disease treatment. It’s all right in front of us. We just make sure we get the policy right, support patients, help the FDA see how to get us there,” Kakkis said. However, the company came across the potential to work with a large patient population, those with Alzheimer’s disease, after doing work on a one-in-a-million-person disease known as galactosialidosis. Their… #lucidquest #genetherapy #celltherapy

#Estimation #Estimatecostofgenetherapy Creating and implementing a novel financial model that estimates the future number of gene therapy approvals across all therapeutic classes, the size of their targeted patient populations, and their prices. We use advanced simulation methods to conduct the analysis. The use of simulation, rather than purely deterministic methods, allows us to capture the inherent risks and uncertainty in costs, revenues, and other parameters of this new therapeutic class

LucidQuest Strategic Insights (lqventures.com) >>> Gene&Cell Therapy >> FDA's CBER chief hints at expanding Sarepta's gene therapy label, sends stock up 25%: Despite a failed confirmatory trial announced in October, the FDA’s Peter Marks, the top regulator for all cell and gene therapies in the US, is signaling a likely expanded label for Sarepta’s Duchenne gene therapy, sending the stock up by about 25% over the past five days. While it’s rare to see a regulator be so supportive of a single company, it’s rarer still to see Marks signaling a likely expanded approval for Sarepta’s Elevidys, which is currently only authorized under the accelerated pathway for ambulatory pediatric patients aged 4 through 5 years with Duchenne, but which the company would like to extend through to 7-year-olds. Investors at the end of October shed 40% of Sarepta’s share price when the confirmatory results came through, showing the difference between Elevidys and placebo was not statistically significant. But Marks looks likely to join his colleagues Janet Woodcock and others who previously helped Sarepta in its earliest days, ushering the company’s first DMD drug, Exondys 51 (eteplirsen), across the finish line despite limited data. And unlike Elevidys, a follow-up confirmatory trial for eteplirsen has never been completed. Marks said at a STAT News event this week that, basically, the failed Elevidys trial didn’t bother him. And he’s been offering bullish comments on the use of the accelerated approval pathway more frequently, saying at a fireside chat a few months ago, “I don’t have any problem with things sitting out there with accelerated approvals for five or 10 years.” The investment bank Leerink Partners said in a note yesterday that Marks’ comments “emphasized regulatory flexibility” with Elevidys, adding, “This is in line with our current thoughts and further supports our belief that Elevidys will likely remain on the market with an expanded label, at least for those ambulatory, while expansion into non-ambulatory patients remains more of a wildcard.” More regulatory updates for Elevidys are expected in early March. #lucidquest #genetherapy #celltherapy

LucidQuest Strategic Insights (lqventures.com) >>> Gene&Cell Therapy >> #ASRS24: Adverum prepares pivotal study for wet AMD gene therapy, touts Phase 2 data: Adverum Biotechnologies’ eye disease gene therapy has traversed a rocky road of safety troubles, but the company — presenting new Phase 2 data in wet AMD — now believes it has a clear shot to a pivotal study early next year. Its candidate, previously known as ADVM-022 and now called ixo-vec, is intended to reduce the frequency at which patients need to receive follow-up injections of Eylea after getting the gene therapy. Among 29 patients who received the dose Adverum intends to take into Phase 3, 76% were injection-free after 26 weeks. Researchers presented the data at the American Society of Retina Specialists’ annual meeting in Stockholm. Another 29 patients received a higher dose, and 83% of these individuals remained injection-free after the same time period. But Adverum is going with the lower dose because it can deliver similar efficacy to the high dose while provoking less inflammation, CEO Laurent Fischer told Endpoints News. “We did a lot of work in the last several years to demonstrate in non-human primates that we could continue to lower the dose,” Fischer said. “We’ve achieved the goal of showing that we can lower the dose by three-to-10 fold from what we tested in the past, and that dose gives a similar level of efficacy.” Ixo-vec is designed to be injected directly into the eye, containing a gene that can prompt patients’ eyes to generate aflibercept (Eylea’s scientific name) on their own. The idea is that a one-time treatment will stop patients from having to receive continuous eye injections, as most find the process burdensome and uncomfortable. It’s a similar concept to a program being developed by 4D Molecular Therapeutics, which also presented new data in Stockholm on Wednesday. Fischer said ixo-vec can separate itself from 4DMT’s program, called 4D-150, because ixo-vec can more reliably induce the cells to express aflibercept. “We have more patients for longer that have been treated with ixo-vec with, I think, higher efficacy and a higher percentage of patients free of injection [than 4DMT’s drug],” Fischer said. Adverum intends to present additional data later this year with longer follow-up, finalize the Phase 3 design in the fourth quarter and then launch the pivotal wet AMD trial in the first half of 2025. Right now, Fischer said he expects the study’s primary endpoint to measure visual acuity after 12 months in a non-inferiority setting compared to Eylea. Ixo-vec is roughly five years removed from a safety scare that saw wet AMD patients taking a much higher dose suffer vision loss despite signs that the treatment improved retinal anatomy. The problems were followed by additional safety concerns that popped up in a diabetic macular… #lucidquest #genetherapy #celltherapy

Gene&Cell Therapy >> Roche moves one Spark hemophilia gene therapy into PhIII, cuts another : As Roche finally puts one gene therapy for hemophilia A into Phase III, it’s discarding another. Roche disclosed the removal of RG6358, or SPK-8016, in its second quarter earnings presentation, where it also noted that a Phase III trial of RG6357, or SPK-8011, has been initiated. The company is aiming to open enrollment for the study, which will be called Keystone1, later this year, a spokesperson confirmed in an email. Both programs are under Spark Therapeutics, a subsidiary of Roche, following a $4.8 billion buyout in 2019. At that time, Spark had already started Phase I/II studies for the two programs, with an eye toward a pivotal SPK-8011 trial within a couple of years. But Roche ultimately delayed the trial initiation to optimize the dose and treatment regimen. Teresa Graham The forthcoming Keystone1 SPK-8011 trial will capture data from a 66-week period and then track patients for 10 years to collect long-term safety and efficacy data, the Roche spokesperson told Endpoints News. When asked about the SPK-8016 cut on a media call, Roche Pharma CEO Teresa Graham said the gene therapy “wasn’t having the impact that we thought that it was going to have.” “When you know that your treatment isn’t going to be able to impact patients the way that you hope, the responsible thing is to refocus your resources in something that you believe will,” she said. Roche CEO Thomas Schinecker added that Roche is looking for “durable, long-lasting effects.” With gene therapies, “you basically have one shot” before patients develop antibodies against the vector used to deliver the therapy, he explained. Thomas Schinecker While Spark was once among the frontrunners to bring a hemophilia A gene therapy to the market, it will now be playing distant runner-up to BioMarin, which landed FDA approval for Roctavian in June after multiple delays and a challenging rollout in Europe. The FDA had initially rejected the therapy and demanded more durability data. SPK-8011, also dubbed dirloctocogene samoparvovec, consists of a bioengineered AAV vector made with the AAV-LK03 capsid, a human factor VIII gene and a liver-specific promoter, according to Roche. At the ASH conference in December, Roche presented new data showing that 21 of 23 patients who received SPK-8011 saw sustained expression of factor VIII after up to five years of follow-up. Among the 21 patients, the annualized bleed rate was reduced by 92%, with a corresponding drop in use of factor VIII replacement. In its Q2 presentation, Roche noted that it’s also scrapped four Phase I programs. In addition to a SQZ-partnered cancer vaccine that it decided not to take an option on after reviewing the data package, it also axed RG6007, a T cell receptor-like T cell engager tested for… #lucidquest #genetherapy #celltherapy