A young man with Duchenne muscular dystrophy has died in Pfizer’s Phase Ib trial of its mini-dystrophin gene therapy, triggering a halt in screening and dosing — and a clinical hold imposed by the FDA.
Pfizer informed the Parent Project Muscular Dystrophy of the death in a community letter. The patient was participating in the non-ambulatory cohort of the trial, the company wrote, adding:
At this time, we do not yet have complete information and are actively working with the trial siteinvestigator to understand what happened.
The gene therapy field remains on high alert for safety concerns surrounding AAV, the workhorse viral vehicle the majority of the field still relies on to deliver their supposed one-and-done cure, after patient deaths and hospitalizations rattled families, clinicians and drug developers alike. In particular, high doses of AAV — which is especially common among gene therapies aimed at the muscle-skeletal system — have been associated with serious side effects and spurred heated discussions.
At 3E14 vg/kg, Pfizer’s PF-06939926 had among the highest doses given in any trial, even with the caveat that everyone measures dosage somewhat differently.
In a closely-watched race with Sarepta, Solid and others to bring forward the first-ever treatment for Duchenne that goes after the root cause of the muscle-wasting disease, Pfizer maintains that the ‘safety and well-being of the patients in our clinical trial remains our top priority.’
‘Gene therapy has the potential to significantly impact the trajectory of DMD disease progression. Nevertheless, it is important to remember that this is a novel therapeutic approach and the scientific community is still learning about the risks and benefits,’ a spokesperson wrote in an email to Endpoints News.
The open-label study was testing PF-06939926, Pfizer’s AAV9 gene therapy candidate, in both ambulatory and non-ambulatory patients. Pfizer had previously studied the same candidate only in ambulatory participants, i.e. those who can still walk.
The spokesperson added that non-ambulatory cohort was enrolled in the US only, ‘and we don’t yet know of potential implications for the ambulatory participants in the Phase 1b or in CIFFREO.’
Safety fears have emerged in the past. Most recently, Pfizer amended the enrollment protocol for its Phase III trial — called CIFFREO — to exclude patients with certain genetic mutations, after investigators flagged severe side effects tied to those mutations. Those included three cases of muscle weakness, two of which included heart inflammation. (The company noted the investigators involved in that study outside of the US, and their respective regulatory authorities, have been notified of the most recent update.)
And in 2020, researchers observed two cases of immune reaction to the treatment — specifically, complement activation leading to thrombocytopenia requiring platelet transfusion and treatment with a complement inhibitor.
Questions still abound as to why safety issues emerge or how to prevent them. Even though some of the adverse events, such as liver toxicity, are well documented, scientists say we need a lot more information to determine why. In the mean time, technical barriers and the wide variability of research methods mean imposing a cap on dosage is virtually impossible, if not meaningless — and a recent expert panel hosted by the FDA to discuss many of the top issues was described by critics as a ‘missed opportunity.’
CALQUENCE is a registered trademark of the AstraZeneca group of companies.
At the 2021 American Society of Hematology (ASH) Annual Meeting & Exposition, blood cancer researchers from around the world gathered virtually to discuss the progress that has been made in the field of hematology. Over the past decade, that progress has been tremendous. We’ve seen not only breakthrough approaches to care, but also significant improvement upon existing novel treatments and exploring combinations within those medicines.1 These advances have transformed expectations of what a blood cancer diagnosis now means for patients. While we’ve come a long way, I believe the most exciting scientific discovery is yet to come, and that future advances will truly transform patient care.
Michel Vounatsos, Biogen CEO (Credit: World Economic Forum/Valeriano Di Domenico)
In a surprise move, Biogen announced Monday that it will cut the price of its controversial Alzheimer’s drug Aduhelm in half, slashing the cost from $56,000 to $28,000.
The sudden discount marks a sudden turnaround for the big biotech as it struggles to turn around a drug whose stuck-in-the-mud sales and political ramifications have sent the company into turmoil and triggered the ousting of its longtime chief scientist. Biogen’s leadership had resisted calls since June to reduce the price of the drug.
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An injectable treatment for the prevention of HIV has been given the go-ahead by the FDA for use in adults and children weighing at least 77 pounds.
Apretude is first given as two injections given a month apart from each other, and then every two months after. Patients are given the option to start treatment with Apretude or the oral cabotegravir Vocabria for four weeks to assess how well to tolerate the drug.
Angie You and Volker Schellenberger, Amunix
Sanofi is crashing the year-end M&A party with a deal of its own.
Immuno-oncology is the name of the game as it swallows Mountain View, CA-based Amunix for $1 billion upfront and up to $225 million in biobucks, tagging a suite of T cell engagers and cytokine therapies as well as a tech platform for making ‘conditionally activated biologics.’
‘The Amunix technology platform utilizes a next generation smart biologics approach to precisely tailor-deliver medicines to become active only in tumor tissues while sparing normal tissues,’ said Sanofi R&D chief John Reed, ‘thus bringing the promise of more effective and safer treatment options for cancer patients.’
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Aldeyra Therapeutics’ shares tanked in premarket trading after the company admitted its dry eye candidate reproxalap missed the primary endpoint in a topline Phase III readout — but who needs the primary?
Despite the late-stage failure, Aldeyra is charging ahead with another Phase III trial, and CEO Todd Brady is confident a secondary endpoint will lead the candidate to success.
‘We continue to advance reproxalap toward NDA submission as we focus on the completion of TRANQUILITY-2 and enrollment in the 12-month safety trial,’ he said in a statement.
Graphic: Alexander Lefterov for Endpoints News
Drug pricing reform has been a political football for years, with both Donald Trump and Joe Biden championing changes during their presidencies. Little has moved the needle on Capitol Hill, however, thanks in part to the drug industry’s powerful lobbyists.
In the most recent example, Democrats tried to allow Medicare to negotiate drug prices — an immediate non-starter for biopharma proponents. After months of negotiation, the measure fell apart in favor of provisions on a small subset of drugs that passed the House but marked a far cry from Biden’s promises and what many activists had hoped for. The bill, included as part of Biden’s broad social policy agenda, now appears dead after Democrats failed to secure 50 votes in the Senate.
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The director of the gastrointestinal oncology program at the University of Chicago Medical Center has been charged by the US attorney in Chicago with insider trading after he made more than $134,000 from stock trades based on an early look at the results of a Five Prime Therapeutics trial.
The US attorney’s office said yesterday that back in early November 2020, Daniel Catenacci, a University of Chicago associate professor with more than a decade of experience who worked with Five Prime on early trials, purchased more than 8,700 shares of the company the morning before it announced positive results from a Phase II trial in treating advanced gastric/gastroesophageal cancer.
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Right as the new Omicron variant is poised to increase rapidly across the US, the federal government has effectively run out of the only monoclonal antibody treatment that works against it, and at least one major hospital system is now halting all mAb infusions.
Late last month, the federal government paused shipments of GlaxoSmithKline and Vir’s mAb treatment sotrovimab in order to conserve supplies of the only treatment that might work against the Omicron variant. Last week, however, HHS told Endpoints News that the move to hold back sotrovimab was unrelated to Omicron, and due to a surplus of Eli Lilly mAbs, which aren’t effective against Omicron.
Brian Culley, Lineage Cell Therapeutics CEO
In a lucrative market for ocular degeneration, Roche has long sat on a gold mine with its drug Lucentis — but the times are changing, and the drugmaker is looking to add to its ocular portfolio. Now, Roche will bet on a regenerative approach to eye disease with a small biotech with some very early but promising data.
Genentech will pay $50 million upfront and a potential $620 million in downstream milestones for licensing rights to Lineage Cell Therapeutics’ OpRegen program, a cell therapy that aims to regenerate healthy versions of retinal pigment epithelial cells in patients’ eyes, the companies said Monday.
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