Memorandum

Lilly/BI’s empagliflozin receives FDA Complete Response Letter (CRL) due to deficiencies at BI manufacturing facility - March 5, 2014

This morning, Lilly announced that it has received a Complete Response Letter (CRL) from the FDA for its SGLT-2 inhibitor candidate empagliflozin, which it developed in partnership with Boehringer Ingelheim (BI). The problem FDA cited is manufacturing, which presumably is addressable and will not require additional studies, which is usually the worst case scenario in CRLs. The CRL cites "previously observed deficiencies" at BI's manufacturing facility - these concerns were first discussed during Lilly's 2014 Financial Guidance Call, when management announced that BI had received a warning letter from the FDA in May 2013 regarding the same manufacturing facility. Although it is uncertain when the next FDA re-inspection might be, we believe that the FDA could require around six months after the inspection to make a decision on whether or not the issues have been resolved and, therefore, on empagliflozin's approval. The agency is not requesting any additional clinical studies or data on the candidate, which suggests the drug profile is fine and that BI simply needs to fix its manufacturing plant - the complexity of manufacturing can vary, of course, and we have no additional information on this front at present. We will be interested to learn what this will mean for the timeline for "empa/lina," the SGLT-2/DPP-4 inhibitor fixed-dose combination that Lilly/BI were hoping to file in late 2014 and the empagliflozin/metformin FDC, which had also been on track for 2014 submission; we imagine delays on these fronts are likely also in store, which is the most negative impact from this news - the companies have not commented on this speculation, however, and we will continue to try to learn more in the coming day.