The new generation of the world's "best-selling" small molecule drug controversy has not been fruitful for the time being, because the two drugs have failed to test...

In Barcelona, Spain, the 2022 European Annual Conference on Cardiology is being held, and at this large-scale four-day academic event, two reports have received much expectation and attention from many people - the results

Both failed, but the problem was not great

Unfortunately, the two phase II trials of the two new generation anticoagulants M and A did not reach the composite endpoint, and the data were not very good

Partial trial endpoint data

The data on M drugs were slightly better, and the incidence of the main efficacy endpoint in the 50 mg and 100 mg bid (twice daily) groups was numerically lower, but there was no obvious dose-response relationship; A is a little more embarrassing, and compared with placebo, it does not reduce the compound event endpoint of occult cerebral infarction or recurrent symptomatic ischemic stroke, and the primary efficacy outcome is not dose-dependent

But that doesn't mean the two drugs don't have a

In the field of chronic diseases, the use of compound endpoints is more than in the field of tumors, because disease progression is slower, and the use of hard endpoints such as OS may wait 10 years for results; At the same time, the demand for sample size in chronic disease trials is also greater, compared with phase III clinical trials with hundreds of people in the field of tumors, thousands of people enrolled in chronic disease trials are only the "starting price", and large phase III clinical studies have tens of thousands of sample sizes abound

By combining a variety of clinical events such as stroke, myocardial infarction, heart failure progression, and hemorrhagic/ischemic events, compound endpoints are obtained and the incidence of events is increased, which not only reduces the trial time, but also greatly reduces the sample size

However, the consequent increase in risk, it is possible that the drug has better data on some events but poor performance on other events, and the more events in the compound endpoint, the greater the risk of trial failure, and the higher

If the new drug research and development is compared to the college entrance examination, reaching the composite end point and comprehensively hanging the control group, it probably means that the qualification of "pre-admission to famous schools" has been obtained, and if it has not reached the composite end point, you can only continue to look for opportunities to see which end point is better improved, and then do a single end point test and continue to spell "college entrance examination results"

Secondary analysis, each has its own highlights

After the compound endpoint failed, the pressure came to the analysts, fortunately both drugs have some bright spots, mainly from the population

Let's start with the M drug

Secondary analysis showed a significant reduction in the risk of recurrent symptomatic ischemic stroke and TIA in the 50 mg group compared with placebo, and the reduction was greatest in patients with intracranial or extracranial atherosclerotic plaque: recurrent symptomatic ischemic stroke or TIA: 8.

summary

BMS and Bayer are old rivals in the field of oral anticoagulants, and apixaban and rivaroxaban are from two companies

Bayer's Rivarsaban went public in 2008, three years ahead of Apixaban, and once had the advantage in

Historically, such a preemptive "latecomer advantage" of the drug is not a minority, Pfizer in the hands of the former ace product Lipitor (atorvastatin), is merckSidon FIC drug Shu Descending (Simvastatin) of the same product, after an iterative update, Lipitor has a stronger lipid-lowering effect, and finally seized more market share, won the "King of Medicine" throne for many years, and even became the first drug with cumulative sales of more than 100 billion US dollars

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