Avanir will receive $10 million upfront from AstraZeneca under the terms of the deal, which gives the Anglo-Swedish drugmaker development and marketing rights to compounds in a new class of treatment, the reverse cholesterol transport (RCT) enhancers. The other $330m is dependent on the achievement of various clinical and sales milestones.
RCT is a natural process that involves the flow of cholesterol from tissues, including the walls of blood vessels, and its subsequent transport to the liver for metabolism and removal from the body. The process is complex, involving several steps, and a variety of specialised transporter molecules and carrier proteins to take cholesterol out of body tissues into the liver. Once cholesterol is taken up by the liver, it can then be transported to the gall bladder for excretion.
RCT enhancers are designed to directly increase the flow of lipids from blood vessel walls by promoting this natural process. "Compounds that enhance this pathway may potentially reverse existing vascular disease in comparison to current agents, which have to date only been shown to prevent disease progression," said AstraZeneca in a statement.
The new agreement comes at a time when AstraZeneca is just starting to make real progress with its 'superstatin' Crestor (rosuvastatin), which has just pushed sales past the billion dollar mark. Plagued with side effect concerns in the early stages of its commercial life - since resolved after the US Food and Drug Administration (FDA) concluded that it was as safe as other drugs in the class - Crestor is now starting to gain momentum.
However, it is still lagging a good way behind arch-rival Lipitor (atorvastatin) from Pfizer, which with annual sales of around $11 billion is the world's biggest-selling pharmaceutical, and is facing competition from Merck & Co and Schering-Plough's Zetia (ezetimibe), now combined with Merck's simvastatin in a double cholesterol treatment Inegy/Vytorin. The latter is tipped to make sales of $1.5 billion this year, helped by its dual effect of inhibiting the absorption of cholesterol from the intestine and its production by the liver, giving it an advantage over statin monotherapy.
The agreement with Avanir gives AstraZeneca an extension to its cholesterol-lowering franchise and the potential for combination therapies - in the future - that could rival Vytorin.