Inside The FDA: Eli Lilly and Co (LLY) Jardiance Aims at Proving Cardiovascular Benefit in Diabetes, Will FDA Agree?

Introduction

On June 28, 2016, the Endocrinologic and Metabolic Drugs Advisory Committee of the Food and Drug Administration (FDA) met to discuss and vote upon a supplemental New Drug Application (sNDA) for Jardiance, codeveloped by Boehringer Ingelheim Pharmaceuticals and Eli Lilly and Co (NYSE:LLY). The drug is an already approved compound that the FDA gave a green light to back in August 2014 for marketing as an adjunct to diet and exercise to improve glycemic control in adults with type II diabetes mellitus.

Subsequent to the approval, the drug was shown to reduce the likelihood of heart attack, stroke and cardiovascular death. Of these three reductions, the latter was the most dramatic as we will go on to discuss in a little bit more detail shortly. This study now forms the basis of the sNDA, and an approval in this indication could vastly increase the drug’s sales potential heading into 2017 and beyond.

The FDA is expected to put out a decision at some point in November, but the advisory panel vote was very close, and there is a high degree of uncertainty as to which way the agency will go.

On August 4, the FDA signed off on the meeting minutes from the advisory panel review meeting, and made them available for public inspection. In an attempt to gauge the chances of the agency giving Jardiance a green light for commercialization as a cardiovascular risk- cutting compound, here’s our interpretation of the minutes, and an outline of our expectations for the drug going forward.

Note: The meeting also discussed the potential for approval of one other sNDA submitted by Boehringer Ingelheim regarding the expanded approval of another diabetes drug, Synjardy. Subsequent to the advisory panel review, and in line with the committee’s recommendation, the agency approved Synjardy in its extended indication on July 20, 2016.

Diabetes Type II

A quick review of diabetes is in order for new readers. Type II diabetes of course is characterized by high blood sugar and a lack of insulin. It occurs from a pathophysiological perspective as the result of insufficient insulin production against a background of insulin resistance.

The best way to think about insulin is as a sort of key that opens and closes the cells in the body to glucose. When we eat, certain enzymes break down complex carbohydrates into glucose. In healthy patients, this glucose then transfers into muscle and tissue cells, where it is stored or used as energy. Insulin is what opens up the cells to allow the glucose to get in. In patients with type 2 diabetes, however, a lack of insulin means the cells aren’t open to glucose absorption and the glucose builds up in the blood.

Additionally, in patients with type 2 diabetes, the liver releases too much glucose in the evening and at night. There’s not enough insulin available to deal with the released glucose, and again, it builds up to high levels in the blood.

This buildup can result in a whole host of complications, including tissue damage, circulation issues, kidney damage, sight and hearing issues, cardiovascular issues, stroke and an increased risk of Alzheimer’s disease.

Globally, type 2 diabetes is a massive problem. In the US alone, 30 million people suffer from diabetes, and it is estimated that more than 8 million remain undiagnosed. Of these numbers, between 90-95% fall into the type 2 diabetes category, with the remainder classed as type 1 which is caused by autoimmunity against the pancreas. Nearly 2 million new diagnoses occur in the US every year, and the condition costs the US government an estimated $250 billion annually.

The World Health Organization (WHO) estimates that globally there are more than 387 million individuals living with the condition.

The current across-the-board standard of care is a combination of diet and exercise (the disease is actually preventable through a combination of these two elements, but by the time symptoms show it is generally too late to reverse onset) and regular insulin administration, generally by way of subcutaneous self-injection.