Annovis Bio recently received a positive safety review for the Phase III trial of buntanetap in patients with early Parkinson’s Disease (PD) (NCT05357989) from the Data and Safety Monitoring Board (DSMB), a big win for the company. Should buntanetap demonstrate good efficacy and safety profiles in the trial, it could be the first α-synuclein-targeting product to enter the market and one of the first potentially disease-modifying agents, but it faces a complex road ahead, says GlobalData, a leading data and analytics company.

The positive safety review from the DSMB enables the trial to move forward as planned, with an estimated completion date in December 2023. GlobalData forecasts that buntanetap will launch in the US and 5EU (France, Germany, Italy, Spain, and the UK) in Q4 2026 and Q4 2028, respectively.

Christie Wong, Pharma Analyst at GlobalData, comments: “The current medications used for the treatment of PD are limited to dopaminergic therapies that provide only symptomatic relief of motor symptoms, leaving ample opportunities for new entrants into the PD market. Importantly, buntanetap may actually possess disease-modifying properties by inhibiting α-synuclein, potentially preventing the formation of toxic aggregates and, in turn, halting disease progression.”

Key opinion leaders (KOLs) previously interviewed by GlobalData agreed that if a disease-modifying or neuroprotective agent was approved for PD, it could bring a major shift in the way these patients are treated. Like Annovis, many companies have been developing first-in-class programs that target α-synuclein. According to GlobalData’s Drugs Database, there are currently 12 products in Phase I-III clinical trial development for PD in the US and 5EU that list α-synuclein as a molecular target.

Roche/Prothena’s prasinezumab, a monoclonal antibody targeting α-synuclein, administered via intravenous (IV) infusion is set to compete with buntanetap. There are two ongoing Phase IIb trials, PASADENA and PADOVA (NCT03100149 and NCT04777331). GlobalData forecasts that prasinezumab will launch in the US in Q4 2029.

Wong adds: “Buntanetap has a few winning attributes over prasinezumab. As well as a first-to-market advantage, it has a convenient daily oral administration compared to prasinezumab’s monthly IV infusion that typically requires administration and monitoring in a healthcare institution.”

However, KOLs expressed concerns about both products’ likelihoods of success, largely because it is still unclear whether targeting extracellular α-synuclein protein with buntanetap or prasinezumab will slow the progression of PD and offer enough functional benefit to PD patients.

Wong continues: “Furthermore, the lack of validated endpoints and biomarkers available to quantify disease-modifying properties of PD drugs remains a major hurdle in the development of novel treatments. Unfortunately, unlike amyloid imaging for Alzheimer’s disease, an α-synuclein imaging tool is not available. As such, advancement in assessing α-synuclein as a biomarker for PD is considered to be a very important step towards developing disease-modifying therapies.”

Targeting α-synuclein as a mechanism of action has yet to be proven in larger Phase III clinical trials, and previous attempts to target this protein have failed. For example, Biogen’s cinpanemab failed in its Phase II trial SPARK (NCT03318523) in February 2021, leading the company to halt its development for PD.

Wong concludes: “Companies developing disease-modifying therapies in PD will be heavily rewarded from the investment in this risky R&D space. If found to slow PD disease progression, drugs like buntanetap and prasinezumab have the potential to revolutionize the treatment of PD.”