We are updating our diabetes models based on recently released information regarding drugs in NDA and further analysis of the likelihood that late stage drugs will have sufficient data to demonstrate cardiovascular safety according to the FDA guidelines released last December. In addition, since the issuance of the new guidelines, more information has come out to estimate the timing of programs in earlier stage development.

The guidelines allow for a meta-analysis of Phase II/III trials, but a question has been whether late stage programs will have enough cardiovascular adverse events to allow for a sufficient statistical analysis in the initial screening process (please see our prior event for more information on the guidelines). Other questions are what type of events the FDA will allow in the analysis and whether uncontrolled extension data can somehow be used. Of note, Takeda recently put out a release stating that the FDA does not believe alogliptin can pass the cardiovascular guidelines and offered to discuss the design of additional studies. On the other hand, the agency has scheduled advisory committee meetings for Victoza (NVO, JNJ) and Onglyza (BMY, AZN, OSIP). We think this implies that the latter two do meet the cardiovascular guidelines under certain analyses, though there could be discussions whether these analyses are sufficiently robust.

FDA officials have said that the meta-analysis should involve controlled one-year studies, but while their comments have suggested this will not be a requirement for drugs currently in NDA, it is still unclear how the agency will apply the requirement to drugs with Phase III programs that are well advanced.

We further discuss the situation for drugs in NDA and late stage Phase III drugs, as well as the timing for earlier stage drugs in the PDF above.

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