2012-2015 US FDA breakthrough treatment drug inventory
Since 1988, the US FDA has developed a number of new drug accelerated approval programs, including Fast Track Identification (1988), Accelerated Approval (1992), and Priority Evaluation (1992) to accelerate the development and review of new drugs for patient needs. Even so, because the existing mechanisms for speeding up drug marketing often require Phase III clinical trial data for drug development, the review speed is insufficient to meet the needs of many patients who urgently need new drugs. The 2012 Food and Drug Administration Safety and Innovation Act (FDASIA) was approved, and the FDA began a new tool for breakthrough therapy designation to effectively promote drug discovery. So what new drugs have been approved by the FDA for breakthrough therapeutic drugs since 2012? What are the characteristics of these new drugs that have been approved for breakthrough therapeutic drugs?
Definition and characteristics of breakthrough therapeutic drugs
Section 506(a) of the US Federal Food, Drug, and Cosmetic Act provides for the determination of a drug as a breakthrough therapeutic drug, “whether used alone or in combination with one or more other drugs, if intended for serious or threatening purposes. The treatment of a disease or condition of life, compared to existing treatments, and preliminary clinical evidence to demonstrate a significant improvement in one or more clinically meaningful endpoints. This was observed significantly in the early stages of clinical development. The clinically effective drug is the 'breakthrough therapeutic drug'.” Breakthrough therapeutic drugs have the following characteristics: 1 possess all the characteristics of fast-track identification; 2 strengthen the effective drug development in the IND (Investigational New Drug) stage Guidance, earliest suitable for Phase I clinical trials; 3 Organizational commitment by senior manager involvement.
Overview of the approval of breakthrough therapeutic drugs from 2012 to 2015
Figure 1 Distribution and age distribution of 72 new breakthrough drug treatments for breakthrough drug treatments published in 2012-2015
Source: Nat Rev Drug Discov. 2015 Sep;14(9):597-8
As of July 2012, the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) received a total of 309. A breakthrough therapeutic drug application. Of these, 29% (90) of the breakthrough therapeutic drug applications were approved, 55% of the applications were rejected, and 16% of the applications have no clear results yet (see Figure 1). Of the 72 drugs that have been identified as breakthrough therapeutic drugs, 63% (45) are antineoplastic, hematological and orphan drugs. In the study of tumors, hematological diseases and rare diseases, new mechanisms of disease action and new drug targets have been continuously discovered, and at present, the proportion of breakthrough therapeutic drugs is high due to the lack of effective treatment methods. However, there is a clear lack of breakthrough therapeutics in certain disease areas such as cardiovascular disease, immune system disease and endocrine system diseases. In the past 2014, most of the breakthrough therapeutic drugs were awarded Phase III drugs (see Table 1).
Table 1 Phase III clinical new drugs approved by the FDA for breakthrough drug treatment from June 2014 to June 2015
Source: Nat Rev Drug Discov. 2015 Sep;14(9):597-8
FDA analysis of the characteristics of breakthrough drug approval
The FDA's identification of breakthrough therapeutic drugs is highly relevant to the indications for the drug. Chronic lymphocytic leukemia, cystic fibrosis, viral hepatitis C infection, and idiopathic pulmonary fibrosis are serious diseases, and there are urgent unmet medical needs. FDA is more likely to grant breakthrough therapeutic drugs to new drugs. And hope that through the breakthrough treatment of drugs can accelerate the listing of a number of new drugs to solve these very urgent medical problems. For example, in 2013-2014, a total of four new drugs for chronic lymphocytic leukemia were awarded a breakthrough therapeutic drug certification, which was subsequently approved by the FDA. The four breakthrough treatments include the CD20-specific monoclonal antibody Ofatumumab developed by GlaxoSmithKline (approved for treatment of chronic lymphocytic leukemia on September 24, 2013) and the CD20-specific monoclonal developed by Roche. Antibody Obinutuzumab (approved for treatment of chronic lymphocytic leukemia on November 1, 2013); Bruton's tyrosine kinase inhibitor Ibrutinib, a small molecule drug targeted by Pharmacyclics/Janssen (February 2014) On the 12th, it was approved for the treatment of chronic lymphocytic leukemia) and the phosphoinositide 3-kinase (PI3Kδ) inhibitor Idelalisib developed by Gilead (approved for the treatment of chronic lymphocytic leukemia on July 23, 2014).
On the contrary, the FDA's identification of breakthrough therapeutic drugs is very strict for some new drugs for treating other diseases. For example, new drug research for anaplastic lymphoma kinase (ALK) has achieved some results, such as Ceritinib developed by Novartis, which was marketed on April 29, 2014 by the US FDA for ALK-positive non-small cell lung cancer. Treatment; Alectinib, developed by Roche, was marketed in Japan for the treatment of ALK-positive non-small cell lung cancer in 2014; AP26113, developed by Ariad, is currently in Phase II clinical trial for the treatment of ALK-positive non-small cell lung cancer. However, in August 2013, the FDA rejected the application of the AP26113 breakthrough therapeutic drug certification developed by Ariad because the AP26113 clinical trial for the treatment of ALK-positive non-small cell lung cancer was too few subjects and the follow-up time was relatively short. . After the later data supplement and communication, the US FDA granted the AP26113 breakthrough therapeutic drug certification developed by Ariad in October 2014, but so far Ariad has not filed a new drug application for AP26113.
Prospects for the future of breakthrough therapeutic drugs
With the development of targeted therapies, oncology drugs, blood system disease drugs, orphan drugs will continue to be the most concentrated disease areas in the future. At the same time, it is expected that drugs for immune system diseases and central nervous system diseases will be able to obtain new drugs for obtaining breakthrough therapeutic drugs.