Obicetrapib

NewAmsterdam Pharma thinks its experimental cholesterol treatment could also slow the progression of Alzheimer's disease (AD).The company is evaluating whether a daily, 10-mg oral dose of obicetrapib, a CETP inhibitor, can lower low-density lipoprotein cholesterol (LDL-C) in the Phase III BROADWAY trial. The 2530 study participants have atherosclerotic cardiovascular disease (ASCVD) and/or heterozygous familial hypercholesterolaemia (HeFH) and are unable to achieve LDL targets with existing therapies. NewAmsterdam also conducted a prespecified substudy of 1727 patients within BROADWAY who had either one or two copies of the APOE4 allele, one of the strongest risk factors for AD. At 12 months, the company assessed participants' plasma levels of p-tau217, a biomarker for AD. Those who had received obicetrapib experienced a statistically significant lower absolute change in p-tau217 compared with the placebo group (p<0.002). Specifically for the 367 patients homozygous for ApoE4, the p value was 0.0215."These findings strongly support a potential preventive strategy for Alzheimer's disease,” said CEO Michael Davidson. "These data further differentiate obicetrapib and underscore the critical role CETP inhibition may have in mitigating the risk of AD progression."The results of the AD biomarker analysis — which will be presented in full at the Alzheimer's Association International Conference (AAIC) in July — add to positive data supporting obicetrapib's cholesterol-lowering capabilities. In December, NewAmsterdam reported that obicetrapib led to a statistically significant mean 33% reduction from baseline in LDL-C at 12 weeks, meeting BROADWAY's primary endpoint. Patients taking the CETP inhibitor also saw a 21% decrease in major adverse cardiovascular events compared to placebo.

Fresh findings from a large clinical trial are helping build the case that an experimental drug for cardiovascular illness could also be useful in combating Alzheimers disease.The drug, known as obicetrapib, is designed to block a protein that regulates cholesterol levels. Three late-stage studies have shown patients treated with it experienced significant reductions in LDL or bad cholesterol. The drugs developer, NewAmsterdam Pharma, disclosed near the end of last year data from the latest of those experiments, titled Broadway, which suggested obicetrapib may also offer some protection from heart disease-related complications like strokes.Now, NewAmsterdam is highlighting results from a pre-planned sub-study of Broadway focused on biological markers of Alzheimers.There, the thinking is that obicetrapibs lipid-lowering effects may safeguard neurons. Researchers believe high levels of LDL cholesterol in the brain contribute to the accumulation of amyloid and tau, the two proteins most closely linked to Alzheimers. And notably, the gene APOE4, which creates a protein that transports cholesterol throughout the brain, is the strongest genetic risk factor for the disease.NewAmsterdam said the sub-study evaluated 1,727 patients, including 367 who carried the APOE4 gene. The main measure researchers looked at was a type of tau protein called p-tau217. Over a yearlong treatment period, levels of this protein diminished significantly across both the broader group and the APOE4 segment, according to NewAmsterdam.Previously, the company ran a small, mid-stage study wherein 13 patients at the early stages of Alzheimers were given obicetrapib and followed for about six months. The experiment showed reductions in two cholesterol derivatives with ties to the disease.The new findings differentiate obicetrapib from other drugs and strongly support a potential preventive strategy for Alzheimer's disease, NewAmsterdams CEO Michael Davidson said in a statement.The outcome stoked excitement on Wall Street, too. Matt Phipps, an analyst at the investment firm William Blair, wrote in a note to clients that there are clearly caveats to this analysis since the sub-study wasnt conducted in Alzheimers disease patients. Even so, taken together with the data from that smaller trial, his team thinks these latest results intriguing and may ultimately provide significant long-term upside to NewAmsterdams stock price.Jefferies analyst Dennis Ding echoed that idea in his own note. While investors have been lukewarm on the opportunity in Alzheimers because of the slow uptake of Biogen and Eisais products, this could be an interesting call option over time and might attract interest from strategic dealmakers.Others were even more bullish. Roanna Ruiz, of Leerink Partners, argued that the Broadway results not only help obicetrapib stand apart from other oral drugs and PCSK9s a separate, closely watched class of cholesterol-lowering medicines but they also allow NewAmsterdam to pursue the blockbuster Alzheimer's market.TD Cowens Tyler Van Buren went as far as to write the data suggest obicetrapib can potentially be the first preventative therapy for Alzheimer's disease patients.NewAmsterdam shares were up about 6% at markets open Monday, though they flattened out by mid-afternoon to trade around $20.20 apiece.NewAmsterdam plans to present more detailed data from its sub-study during the Alzheimers Association International Conference in Toronto at the end of July. The company said in January that data from its trio of late-stage studies should support approval filings to global drug regulators. A submission to the European Medicines Agency is planned for the second half of this year. '