Second chances
This week, Roche's Genentech signed a license agreement with Sangamo Therapeutics to develop intravenous genomic medicines to treat certain neurodegenerative conditions, including Alzheimer’s disease.
It’s an interesting tie up given that Roche has not seen a lot of success with Alzheimer's treatments and Sangamo has struggled with neurodegenerative partnerships as of late.
Back in 2019, Roche and development partner AC Immune announced that they were dropping a phase 3 trial of crenezumab, an amyloid-targeting antibody, that was being developed to target early Alzheimer’s. Then, in November 2022, Roche announced that another experimental Alzheimer's drug, gantenerumab, also an an amyloid-targeting antibody, failed to slow the progression of the disease in two large late-stage clinical trials.
But it seems that Roche, through its Genentech arm, wants another shot at Alzheimer’s via Sangamo’s epigenetic regulation capabilities — proprietary zinc finger repressors that are directed to the tau gene. According to Sangamo, these zinc finger proteins are naturally occurring proteins in humans which can recognize and bind to specific DNA sequences. Their natural function is to activate or repress the expression of human genes by turning them on or off.
It’s good news for Sangamo too, who slashed both its pipeline and workforce back in April of last year, after both Novartis and Biogen walked away from separate neurodegenerative deals. The Biogen deal specifically involved using Sangamo’s zinc finger protein transcription factor to target Alzheimer’s.
Recent findings from Harvard University researcher David A. Sinclair posits that aging is a treatable by focusing on the epigenome. While it has sparked debate, it has also ignited considerable interest in epigenetics and how we view — and treat — aging. (Read all about it in next month's cover story.)
The Roche-Sangamo partnership will definitely be one to watch and I look forward to seeing some clinical results in this space. —Karen Langhauser
Weight loss drugs beyond obesity treatment
This week, Novo Nordisk decided to pull back its FDA application for expanding the use of Wegovy to treat heart failure with preserved ejection fraction (HFpEF).
The move, shared in their latest financial report, came after some back-and-forth with the FDA. Instead of pushing forward now, the company plans to resubmit the application in early 2025, this time with extra data, including results from a kidney outcomes trial called FLOW, which looks at the effects of a weekly semaglutide injection.
For context, HFpEF is a condition where the heart's muscles get stiff, leading to less blood being pumped out, which can cause serious health issues.
These findings were initially sent to the FDA and European regulators for review earlier this year, in January. If the expansion eventually goes through, it would be the second time Wegovy was granted a broader label. Just in March, the FDA approved it for reducing the risk of major cardiovascular events, like heart attacks and strokes, in adults with overweight or obesity, based on data from the SELECT trial.
Several GLP-1 receptor agonists, like semaglutide (marketed as Wegovy and Ozempic) and liraglutide (marketed as Saxenda and Victoza), are now being explored for additional medical indications beyond diabetes and obesity. The success of these GLP-1 inhibitors in weight management has sparked interest in their broader therapeutic applications, with ongoing trials aimed at expanding their use in treating conditions related to metabolic syndrome and cardiovascular health.
Semaglutide is being studied for its effects on not just heart failure, but also chronic kidney disease, non-alcoholic steatohepatitis (NASH), a serious liver condition, and Alzheimer's. Similarly, liraglutide has been researched for its potential to reduce the risk of cardiovascular events in patients with obesity and diabetes.
Eli Lilly is also seeking expanded approval for its daibetes and weight loss drug, tirzepatide, after phase 3 trials showed it could significantly reduce the severity of obstructive sleep apnea by up to 63% in adults with moderate-to-severe OSA and obesity.
The exploration of GLP-1 receptor agonists for new medical uses could result in more versatile treatments, potentially addressing not only diabetes and obesity but also a broader spectrum of serious health conditions, including those that often occur alongside obesity, such as heart failure and chronic kidney disease. — Andrea Corona
