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Gene&Cell Therapy >> Stealth Bio gets FDA adcomm for previously rejected ultra-rare disease drug: Seven years after Stealth BioTherapeutics landed a fast track designation from the FDA, the agency has finally agreed to review the company’s application for an ultra-rare, genetic Barth syndrome treatment. Known as elamipretide, the drug will face an FDA advisory committee. The application won’t get a priority or accelerated review from the agency, the Massachusetts-based company said Monday. The adcomm is likely to feature a tough discussion and vote because there are no other approved treatments for the fatal disease, and Stealth is submitting data from an open-label extension compared to a retrospective natural history study, and additional supporting efficacy and safety data from a natural history study. The agency has yet to officially schedule the meeting, but it’s likely to come within the next several months. Monday’s announcement is the first glimmer of hope for Stealth since October 2021, when the FDA refused to even review its prior application for elamipretide, just months after the agency questioned whether there were adequate clinical data. Reenie McCarthy “We are pleased that the FDA has not only filed our NDA for Barth syndrome but has also committed to a transparent review process with its decision to convene an advisory committee,” Stealth CEO Reenie McCarthy said in a statement. “We welcome the input of committee experts to advise FDA on the seriousness of this devastating disease and the urgency of the unmet need, including in light of FDA’s puzzling review designation.” Stealth previously said it submitted the application not on the basis of new data but because Barth syndrome patient advocates petitioned the company. The Barth Syndrome Foundation asked Stealth to do so in November 2020 despite knowing the FDA’s hesitation, noting seven Barth patients — or 3% of the world’s Barth population — died in the preceding 13-month period. Elamipretide has been the topic of frequent meetings over the last several years between Stealth and the FDA’s Division of Cardiology and Nephrology. In 2021, the company disclosed that the agency asked Stealth to run another Phase 3 study, since data from patients on an open label extension of a previous trial were “unlikely to add meaningfully to the evidence to support an NDA.” #lucidquest #genetherapy #celltherapy

LucidQuest Strategic Insights (lqventures.com) >>> Gene&Cell Therapy >> Stealth BioTherapeutics CEO discusses surprise adcomm support for ultra-rare disease drug: This week, Stealth BioTherapeutics CEO Reenie McCarthy faced a seemingly insurmountable roadblock with the company’s drug for the ultra-rare, fatal mitochondrial disease Barth syndrome. FDA reviewers had extensively questioned the data supporting the drug’s efficacy. And the agency had already turned down Stealth once. Instead, the advisory committee on Thursday voted 10-6 in support of the drug, following testimony from patients and their families, as well as doctors who had treated patients with it. The result was a substantial win for the small, 50-person private company and its CEO. McCarthy joined Endpoints News via Zoom on Friday to discuss the surprise vote. “We’ve had a lot of ups and downs along the way, and we really tried to keep progressing the program despite some of the disappointments because of the strong belief that we had a drug that was working for patients living with this terrible disease,” McCarthy said. Barth syndrome affects about 130 American boys, and 80% don’t survive past 5 years of age. However, Stealth’s proposed indication for the drug is for 12 years and older, and the population in which the drug was studied was mostly older teenagers and children. “That’s an FDA decision,” McCarthy said, noting there are about 20 to 25 boys on the drug through an expanded access program. “We certainly profiled some of our expanded access in our presentation, really to speak to the safety that we’ve seen in younger children.” She said the company has had requests for the drug from 10 countries and a dozen US hospitals, noting patients and their families don’t pay for treatment under those expanded access efforts. The FDA has until Jan. 29, 2025, to make a final approval decision. McCarthy declined to discuss potential pricing ahead of an elamipretide approval, and said the company plans to conduct a pharmacokinetic study in younger children to optimize dosing. “You know what the price tags of drugs for super-rare diseases are,” McCarthy said. “We’re going to have to take that into consideration. But super-rare diseases are a little bit less of a problem from a payer perspective as well, because there’s a lot less patients affected by them.” CDER Director Patrizia Cavazzoni, who typically doesn’t speak at advisory committee meetings, made a comment just prior to Thursday’s vote about regulatory flexibility and how the agency is evolving its work in ultra-rare indications. McCarthy said it was the first time anyone in the FDA’s leadership had indicated that there might be some flexibility afforded to elamipretide. #lucidquest #genetherapy #celltherapy

Gene&Cell Therapy >> Stealth BioTherapeutics CEO discusses surprise adcomm support for ultra-rare disease drug: This week, Stealth BioTherapeutics CEO Reenie McCarthy faced a seemingly insurmountable roadblock with the company’s drug for the ultra-rare, fatal mitochondrial disease Barth syndrome. FDA reviewers had extensively questioned the data supporting the drug’s efficacy. And the agency had already turned down Stealth once. Instead, the advisory committee on Thursday voted 10-6 in support of the drug, following testimony from patients and their families, as well as doctors who had treated patients with it. The result was a substantial win for the small, 50-person private company and its CEO. McCarthy joined Endpoints News via Zoom on Friday to discuss the surprise vote. “We’ve had a lot of ups and downs along the way, and we really tried to keep progressing the program despite some of the disappointments because of the strong belief that we had a drug that was working for patients living with this terrible disease,” McCarthy said. Barth syndrome affects about 130 American boys, and 80% don’t survive past 5 years of age. However, Stealth’s proposed indication for the drug is for 12 years and older, and the population in which the drug was studied was mostly older teenagers and children. “That’s an FDA decision,” McCarthy said, noting there are about 20 to 25 boys on the drug through an expanded access program. “We certainly profiled some of our expanded access in our presentation, really to speak to the safety that we’ve seen in younger children.” She said the company has had requests for the drug from 10 countries and a dozen US hospitals, noting patients and their families don’t pay for treatment under those expanded access efforts. The FDA has until Jan. 29, 2025, to make a final approval decision. McCarthy declined to discuss potential pricing ahead of an elamipretide approval, and said the company plans to conduct a pharmacokinetic study in younger children to optimize dosing. “You know what the price tags of drugs for super-rare diseases are,” McCarthy said. “We’re going to have to take that into consideration. But super-rare diseases are a little bit less of a problem from a payer perspective as well, because there’s a lot less patients affected by them.” CDER Director Patrizia Cavazzoni, who typically doesn’t speak at advisory committee meetings, made a comment just prior to Thursday’s vote about regulatory flexibility and how the agency is evolving its work in ultra-rare indications. McCarthy said it was the first time anyone in the FDA’s leadership had indicated that there might be some flexibility afforded to elamipretide. #lucidquest #genetherapy #celltherapy

I am deeply pleased to have one of my valuable research papers finally published, thankfully in the #WebOfScience #Q1 journal, #FoodAndChemicalToxicology, within the #Toxicology discipline. A research to which I've put too much efforts and thinking! I consider it a shifting point in delving deeper into the mechanistic pathways involved in diseases. For me, this is my first investigation into #ferroptosis, the non-apoptotic cell death mechanism which is gaining much attention now. In this study, we explored the role of ferroptosis in #gentamicin-induced acute #kidney injury and the potential renoprotective effects of #lactoferrin via attenuating ferroptosis. Lactoferrin is an iron binding protein which is known for its wide therapeutic uses, however as an iron scavenging drug, it was quite tempting to see if it can modulate the #iron overload-mediated cell death or ferroptosis. I am truly excited about the potential clinical applications that these findings may bring 🫶🏻🙏

🔷 Pfizer announced today that the U.S. Food and Drug Administration FDA has approved BEQVEZ™ (fidanacogene elaparvovec-dzkt) for the treatment of adults with moderate to severe hemophilia B who currently use factor IX (FIX) prophylaxis therapy, or have current or historical life-threatening hemorrhage, or have repeated, serious spontaneous bleeding episodes, and do not have neutralizing antibodies to adeno-associated virus serotype Rh74var (AAVRh74var) capsid as detected by an FDA-approved test. 🔷BEQVEZ is a one-time treatment that is designed to enable people living with hemophilia B to produce FIX themselves rather than the current standard of care, which requires regular intravenous infusions of FIX that are often administered multiple times a week or multiple times a month. https://lnkd.in/dFhgJQNn

What happens when your own immune system attacks you? We'll give you a hint: it's not fun. Inflammation from overactive immune systems causes a wide range of diseases from arthritis to psoriasis. Greg Timblin, CEO of Inapill, has a plan to change that by combining the safety and affordability of over-the-counter NSAIDs with the strength of biologics. Read our latest #TenantSpotlight to learn more about the fascinating science behind Inapill's much-needed technology. https://lnkd.in/gBXiTnUK Also featuring Ingrid Caton, and Venkat Reddy & David Moffat of General Inception

🧬 Have you ever heard of Niemann-Pick disease? It is a rare genetic lysosomal storage disorder that results in progressive neurological symptoms and organ dysfunction, and is ultimately fatal, as individuals affected only live for around 13 years on average. 💔 But there is finally some good news for patients affected by this devastating disease. The FDA has recently approved the first two treatments for it in the space of a week; one is Zevra Therapeutics’ Miplyffa and the other is IntraBio Inc’s Aqneursa. 💊 🔎 Read our latest article to find out more about these approvals! 👇 https://lnkd.in/d6Ap22Cw #NiemannPickdisease #raredisease #geneticdisorders #biotechbreakthrough #healthcareinnovation #pharmanews #patientcare #medicalresearch

Gene&Cell Therapy >> FDA approves J&J and Legend’s Carvykti for second-line multiple myeloma: The FDA has expanded the label for Johnson & Johnson and Legend Biotech’s multiple myeloma CAR-T therapy to make it a much earlier treatment option for patients, J&J announced late Friday night. The regulator approved Carvykti for multiple myeloma patients who have received at least one prior line of therapy. The cell therapy was first approved in 2022 as a fifth-line option, making it available only to patients who’d already exhausted many of their treatment choices. It generated $500 million in global sales last year, and TD Cowen analysts expect the therapy to bring in $950 million in sales this year following the label expansion. According to a J&J presentation, there are around 21,000 eligible multiple myeloma patients in the fourth line and later, and 118,000 in the second and third lines. The expanded label is for patients who have previously been treated with a proteasome inhibitor and an immunomodulatory agent, and are refractory to lenalidomide. Though the label expansion means the patient population indicated for Carvykti is now significantly larger, Legend Biotech CEO Ying Huang told Endpoints News that the company expects the majority of patients receiving the therapy this year to still be from later-line settings. Beyond that, Huang highlighted the potential of the therapy for second-line patients, noting that they likely have received fewer multiple myeloma treatments that suppress the immune system. In later-line patients, “the quality or the quantity of the immune cells you collect in the apheresis process may not be as good compared to patients who had only one prior line,” Huang said. “That is why we think the scientific rationale provides a strong reason why we want to pivot to second line patients rather than third-, fourth-, or fifth-line and beyond.” The FDA on Friday also approved an expanded label for Bristol Myers Squibb and 2seventy bio’s competing multiple myeloma CAR-T therapy. Abecma is now available to certain patients as a third line of treatment. In 2021, it became the first approved BCMA-directed CAR-T therapy. A panel of outside experts in March voted unanimously in favor of Carvykti in earlier lines of treatment, though the FDA had raised concerns about higher death rates in the first few months of the clinical study in patients who received Carvykti compared to those who were on standard care. But the FDA’s advisory committee agreed that the long-term survival benefits outweighed the risks. In a key clinical trial, patients who received Carvykti had a higher death rate until about 11 months into the study, after which they had a lower rate of death. Carvykti cut the risk of disease progression or death by 59% compared to standard therapy in the Phase 3 study called CARTITUDE-4. Both Carvykti… #lucidquest #genetherapy #celltherapy

LucidQuest Strategic Insights (lqventures.com) >>> Gene&Cell Therapy >> FDA approves J&J and Legend’s Carvykti for second-line multiple myeloma: The FDA has expanded the label for Johnson & Johnson and Legend Biotech’s multiple myeloma CAR-T therapy to make it a much earlier treatment option for patients, J&J announced late Friday night. The regulator approved Carvykti for multiple myeloma patients who have received at least one prior line of therapy. The cell therapy was first approved in 2022 as a fifth-line option, making it available only to patients who’d already exhausted many of their treatment choices. It generated $500 million in global sales last year, and TD Cowen analysts expect the therapy to bring in $950 million in sales this year following the label expansion. According to a J&J presentation, there are around 21,000 eligible multiple myeloma patients in the fourth line and later, and 118,000 in the second and third lines. The expanded label is for patients who have previously been treated with a proteasome inhibitor and an immunomodulatory agent, and are refractory to lenalidomide. Though the label expansion means the patient population indicated for Carvykti is now significantly larger, Legend Biotech CEO Ying Huang told Endpoints News that the company expects the majority of patients receiving the therapy this year to still be from later-line settings. Beyond that, Huang highlighted the potential of the therapy for second-line patients, noting that they likely have received fewer multiple myeloma treatments that suppress the immune system. In later-line patients, “the quality or the quantity of the immune cells you collect in the apheresis process may not be as good compared to patients who had only one prior line,” Huang said. “That is why we think the scientific rationale provides a strong reason why we want to pivot to second line patients rather than third-, fourth-, or fifth-line and beyond.” The FDA on Friday also approved an expanded label for Bristol Myers Squibb and 2seventy bio’s competing multiple myeloma CAR-T therapy. Abecma is now available to certain patients as a third line of treatment. In 2021, it became the first approved BCMA-directed CAR-T therapy. A panel of outside experts in March voted unanimously in favor of Carvykti in earlier lines of treatment, though the FDA had raised concerns about higher death rates in the first few months of the clinical study in patients who received Carvykti compared to those who were on standard care. But the FDA’s advisory committee agreed that the long-term survival benefits outweighed the risks. In a key clinical trial, patients who received Carvykti had a higher death rate until about 11 months into the study, after which they had a lower rate of death. Carvykti cut the risk of disease progression or death by 59% compared to standard therapy in the… #lucidquest #genetherapy #celltherapy

Gene&Cell Therapy >> FDA raises concerns of 'early deaths' in Abecma and Carvykti multiple myeloma trials: An FDA advisory committee will vote Friday on whether two CAR-T therapies, Carvykti and Abecma, have a favorable benefit-risk ratio in earlier lines of multiple myeloma treatment. But regulators say early deaths among those who received the cell therapies in trials create uncertainty around their benefit in those indications. Abecma and Carvykti are currently approved as fifth-line treatments for multiple myeloma, a blood cancer that causes most patients to eventually relapse. Bristol Myers Squibb and 2seventy bio have applied to move Abecma, also known as ide-cel, up to the third-line setting, highlighting the importance of using “the most effective therapies early in the treatment paradigm.” The CAR-T therapy significantly lengthened the amount of time before patients saw their disease progress compared to other standard therapies in a Phase III trial. But regulators also noted a higher rate of death in the Abecma arm for up to 15 months. The advisory committee will be asked to discuss whether that risk of early death is “acceptable in the context of the clinical benefit.” “Furthermore, additional follow-up of overall survival even if statistically significant, is unlikely to overcome the increased risk of early deaths,” the FDA wrote in briefing documents released on Wednesday. BMS told Endpoints News on Wednesday that it remains “confident in the safety profile and clinical value of our cell therapies.” In its own briefing documents, BMS attributed the differences in early death rate to patients who never received ide-cel, adding that most early deaths were caused by disease progression. “Early deaths were not due to ide-cel related mortality nor due to manufacturing delays,” the company said. BMS added that the overall survival results were distorted by crossover patients who started in the comparator arm but switched to the Abecma arm after experiencing disease progression. “It is important to note that KarMMa-3 Study was not powered to detect an OS benefit and the cross-over confounds the interpretation of the OS results,” it wrote. Regulators also noted a higher rate of early deaths in the CAR-T arm in the first several months of the Carvykti study, despite also having a statistically significant effect on progression-free survival. Johnson & Johnson and Legend Biotech are looking to bring Carvykti, or cilta-cel, to second-line patients. The FDA said it “is unclear whether the overall benefit-risk assessment is favorable; specifically, whether additional data is needed to support such an assessment.” J&J also said in briefing documents that patients in the Carvykti arm saw disease progression before they began treatment. “Therefore, the imbalance is not related to toxicity associated… #lucidquest #genetherapy #celltherapy