David, could you tell me first of all about the clinical context of what you’re doing here? What was it that you were taking on, what challenge?
The challenge that these two studies are taking on is a wicked problem that we’ve known for a long time and that is of cachexia; that once people start to use muscle as their energy substrate in advanced disease it’s a real problem. It limits the therapies we can give and, importantly, it looks at prognosis for these people.
And what have been the options up to now and what is anamorelin?
The options to date have been progestational agents like megestrol, steroids such as dexamethasone, but these have had limited ability to actually change lean body mass. They may have increased weight overall without oedema being the only cause of that increase in weight but what we’re talking about here is the ability to sustainably increase lean body mass. Anamorelin is the first ghrelin agonist that is available. Ghrelin, as you know, is released by the stomach in response to food and has effects on both appetite and metabolism. Its metabolic effect is one of anabolism so it lays down muscle and helps us in that area.
So you conducted the ROMANA 1 and 2 studies, what did you find?
ROMANA-1 and ROMANA-2 studies are multi-site international randomised placebo-controlled trials where participants were randomised in a 2:1 fashion to anamorelin or placebo. Importantly, lean body mass was greater in both studies, while the control group continued to lose lean body mass. Whole body weight was improved in both studies while the control group continued to lose weight. Importantly, patient associated factors for the functional assessment of anorexia and cachexia were far better in the anamorelin arms of both studies than in the placebo.
It’s a new agent, though, what about toxicities?
This is a new agent and it was incredibly well tolerated. As one would expect from ghrelin being an anabolic substance, what we have are a number of people with hypoglycaemia, which was well controlled easily, and a very small number of people who became overtly diabetic, again managed as we would control any diabetes in this setting.
What then could be the clinical implications?
The clinical implications are really very exciting. There’s every chance that this is the beginning of a generational change. After all, the loss of lean body mass, the use of muscle as the energy substrate, is the beginning of a final common pathway for so many cancers. If we can shift that then we potentially can shift the therapies we give. We are waiting to see the survival data for one year continuation studies and that will be available in the next few months but this is exciting. This is a generational change.
And the take home message, briefly, for cancer doctors, what would that be?
The take home message is that we have a new agent, a novel agent, that is able to increase lean body mass in people with advanced cancer in a way that we haven’t seen before. It opens up therapeutic options and we’re very excited by the opportunities that it may offer also in terms of prognosis but we’re yet to see those data.
