Me-too: First-in-class wants to make a pill, we're too hard

The process of pioneering drug research and development is like looking for a needle in a haystack, with large investment and high risk, along with great unknowns, and a very high failure rateIn this long process, the drug target is indeed proven throughout, even on, even after the drug market still needs to be in the "real world" to further test the drugability of the target, which is not short of many cases of tragic pre-dawn research and developmentrisksdeveloping First-in-class drugs
First-in-class development is a Russian roulette, gambling in many of the "bad luck" was blown outSuch as the anti-inflammatory drug Rofecoxib, which was introduced in 1999 to treat arthritis and acute pain, because of its good efficacy, Rofeb had sales of $2.5 billion in 2003 and about 80 million patients worldwide had taken the drug, but in subsequent studies it was found to cause serious adverse cardiovascular system reactions, such as heart disease and moderate strokeMerck also announced a worldwide recall of Rofibu in 2004, possibly the largest prescription drug recall in historyThe incident also raises global questions about the possibility of cyclooxidase 2 (COX2) being a drug targetIt can be seen that the drug target can not be proved overnight, the need for long-term repeated confirmation, even a successful market drug, may not really achieve the causality between the drug target and treatment applicationAnd the first drug must be targeted at a new role target, its research and development process of the hardships can be seen in generalalso like Pfizer's cholesterol ester transfer protein (CETP) inhibitor Tosechep (2, Tolcetrapib and Merck's Anacetrapib failed after 30 years of research and clinical trials, with Pfizer, the project's leader, investing more than $800 million in research and development and conducting Phase III clinical trials for more than 15,000 people, but eventually having to terminate the project in 2006 due to the risk of adverse cardiovascular reactions, proving that CETP is not suitable for drug targetsAnti-AD new drugs based on targets such as beta-amyloid, 5HT6 and PPAR are the hardest hit by new drug development, with more than 400 clinical trials conducted between 2002 and 2012 being approved only by Memantine ( 4, Memantine ) and not spared in the next seven yearsof course also have the lucky ones, such as hydroxymethyl diacid- coenzyme A (HMG-Coase) is the target of the development of cholesterol-lowering drugs, in blocking the early stage of the synthesis of cholesterol-lowering reactions to inhibit the synthesis of six carbon fragments, there are no other significant adverse reactions, HMG-CoA reductase is also considered a high-quality target for drug developmentthe risk of developing Me-too drugs is not small
Me-too is a follow-up and supplement to First-in-class drugs, and later on, it has become an important part of the creation of new drugsSince the target has been proven to be medicinal, the development of Me-too drugs does not require target confirmation, the risk is relatively low, and the difficulty seems to be smallIn fact, this advantage was only obvious in the 1980s, when the new drug creation concept was not yet full, First-in-class drugs in pharmacological activity and efficitary optimization is not sufficient, leaving me-too drugs beyond the space, resulting in similar First-in-class drugs are rarely better than the best drugs in the Me-too drug For example, the fifth listed drug, atoflavatin, which lowers cholesterol, is better than the first drug, lovastatin, and the antibacterial drug, the anti-oxyfluoxax, is better than the first nofluoroxatin But this century, First-in-class drugs in the activity and efficibility of the optimization is more adequate, patent coverage is also extensive, so that The Me-too drug research and development space is smaller, coupled with the drug regulatory department requires successors better than (at least not inferior to) First-in-class drugs, thus exceeding the difficulty also, due to the long drug development cycle, First-in-class patent expiration and Me-too drug market time is similar, sales and market risk increased, such as a batch of hypoglycemic drug type 2 sodium glucose co-transit protein (SGLT2) inhibitors in a short period of time intensive market, cangliflozin, 2013), Dapagliflozin (2014) and Apalenet (empagliflozin, 2014), even though they were all done in a pioneering way and came out one after another, the competition was equally fierce Me-too is a follow-up supplement to The First-in-class drug, but it has to be a degree, on the one hand, it is better than (or not inferior) First-in-class drugs, and there are limited quantities due to limited market capacity Precision medicine requires the precise creation of specific drugs, so Me-too drugs need to set clear goals and targets In the efficacy of drugs, drug generation, safety, materialized properties (often affect the route of administration, dosage and frequency) and so on, whichever advantages the existing drugs, there is merit Overcoming the resistance of chemotherapy drugs is an eternal theme in the development of new drugs, and the innovation of Me-too drugs is significant The target-as-the-core First-in-class creation, by the molecular - cell , animal model , patient transformation in many uncertainties, unexpected success has a lucky factor The ansopathy of kinase inhibitors to anti-tumor drugs is "where to hit" and it is difficult to "point where to hit where to go" The most difficult to determine in the ADME of the drug generation is D, the distribution of the drug in vivo to a large extent determines selectivity, safety and indications, so in this sense, the development of high-quality Me-too drugs there is a lot of room References 1: On Me-Too 2 Innovative Drug Research and Development Methods and Strategies