Sanofi resubmitted the application which the FDA accepted in September 2015, by which time Sanofi had lost the lead in the field of anti-diabetic drugs to Novo Nordisk. Lixisenatide received FDA approval on July 28, 2016.In 2010, Sanofi extended a license agreement it had with Zealand for lixisenatide to allow Sanofi to combine it with insulin glargine, which was Sanofis best selling drug at the time, with sales of around €3 billion in 2009. Sanofi planned to start the Phase III trial that year. Sanofi submitted the new drug application in December 2015 for the combination and spent a US$245M priority voucher to gain a faster review, to try to outrace Novo Nordisk’s Xultophy, a similar combination drug of Novos insulin Tresiba and Novos GLP-1 agonist Victoza. Sanofis application was considered by the same Endocrinologic and Metabolic Drugs Advisory FDA Committee that was considering lixisenatide as a single agent. In May 2016 by a vote of 12–2, with several members of the committee expressing reservations about Sanofis plans to offer two pens with different ratios of insulin glargine and lixisenatide - one for people who had never taken insulin before and one for people who had; there was also concern about how to handle dosing when switching people from a single drug regimen to the combination drug. In August 2016 the FDA told Sanofi that it was delaying a final decision for three months, and asked Sanofi for more data on how people used the delivery devices.
Ascending cholangitis, also known as acute cholangitis or simply cholangitis, is inflammation of the bile duct, usually caused by bacteria ascending from its junction with the duodenum (first part of the small intestine). It tends to occur if the bile duct is already partially obstructed by gallstones.Cholangitis can be life-threatening, and is regarded as a medical emergency. Characteristic symptoms include yellow discoloration of the skin or whites of the eyes, fever, abdominal pain, and in severe cases, low blood pressure and confusion. Initial treatment is with intravenous fluids and antibiotics, but there is often an underlying problem (such as gallstones or narrowing in the bile duct) for which further tests and treatments may be necessary, usually in the form of endoscopy to relieve obstruction of the bile duct. The word is from Greek chol-, bile + ang-, vessel + -itis, inflammation. Signs and symptoms
A person with cholangitis may complain of abdominal pain (particularly in the right upper quadrant of the abdomen), fever, rigors (uncontrollable shaking) and a feeling of uneasiness (malaise). Some may report jaundice (yellow discoloration of the skin and the whites of the eyes).Physical examination findings typically include jaundice and right upper quadrant tenderness. Charcots triad is a set of three common findings in cholangitis: abdominal pain, jaundice, and fever. This was assumed in the past to be present in 50–70% of cases, although more recently the frequency has been reported as 15–20%. Reynolds pentad includes the findings of Charcots triad with the presence of septic shock and mental confusion.