Clinical success rate, drug development

Clinical success rates and attrition rates by phase of clinical trial for new drugs are important indicators of how effectively companies are utilising drug development resources. The proficiency with which this is done reflects a complex set of regulatory, economic and company-specific factors. Success rates differ by therapeutic class, and t)q)ically vary from about 28% success rate for an anti-infective compound to 12% for respiratory drugs. Table 9.3 shows the details. 

Therapeutic antibodies must be distinguished as mAbs (and derived products) and polyclonal antibodies when discussing their different pharmacokinetic properties and therapeutic applications. mAbs are already - and will in the future - be much more important in drug development and applied pharmacotherapy due to their favorable properties and higher clinical success rates compared to polyclonal antibodies. Thus, although both types of antibody will be discussed in the following sections, most emphasis will be placed on mAbs. 

DiMasi, J.A., Success rates for new drugs entering clinical testing in the United States, Clin. Pharmacol. Therap., 58,1-14,1995 DiMasi, J.A., Trends in drug development costs, times and risks. Drug Inform. /., 29, 375-384,1995. 

As important as - or even more important than -speed of development, is the success rate of the overall process, which must be increased. It has been estimated (J DiMasi, personal commimic-ation) that increasing the success rate by 10% across a portfolio of drugs at all stages of clinical development would have the same effect on development costs as reducing the development time by more than 20%. 

The number of new chemical entities (NCEs) approved by the U.S. FDA has dropped in the last decade (41) and the average success rate, from the first-in-human studies to registration, is only 11% (42). The lack of drug efficacy and safety account for around 30% of the failures in the clinic (42). Thus, the ability to determine drug safety and efficacy early in the discovery process should help in reducing the failure rate during the costly development studies, and in the end it would produce better and safer drugs (43). 

Drug discovery requires a host of inputs, new ideas, design and synthesis of substances, evaluation of preclinical toxicity tests in animals, clinical studies in human volunteers, permission to market the drug, postmarketing studies of safety, and comparison with other medicines. Drug development is highly technical and enormously expensive, with a success rate of 1 in 10,000 compounds. 

The late stage NP-derived compounds discussed in this chapter originate from research undertaken at least ten years ago. This is demonstrated by Tufts CSDD data, which shows there is an average time of 8.5 years from the start of clinical testing to FDA approval with a 21.5% success rate.267 As a consequence, late stage clinical compounds represent a window into the past and certainly do not reflect the current state of NP-derived drug development. 

DiMasi, Joseph A., Risks in New Drug Development Approval Success Rates for Investigational Drugs, Clinical Pharmacology Therapeutics, May 2001. 

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