We have been skeptical of MariTide for a while now, mostly because it makes trial participants want to close their eyes and pray for it to stop. The new phase 2 results are out, and while the weight loss numbers might look good on the surface, 20% for people without diabetes and 17% for those with it, the reaction has been far from bullish. Investors were not cheering. They were, as my kids call it, “spicy burping”.
Amgen confirmed today what many of us have been warning about for months. This GLP-1rs plus GIP receptor blocker may drive weight loss, but it does so with a side of vomiting that would put most cancer treatments to shame. The data showed vomiting rates reaching close to 90% in some arms of the trial. Not just nausea. Actual vomiting. And it was the leading reason people dropped out.
Tirzepatide, which activates both GLP-1 and GIP receptors, appears to have an anti nausea effect built in. In contrast, MariTide blocks GIP and the result has been nothing short of a mess. It is one thing to push through mild discomfort for the sake of better health. It is another to live with a bucket by your bed for a year.
Amgen says it will reduce dosing and frequency in phase 3 to try to improve tolerability. That is not fine tuning. That is a major rewrite. You cannot scale a treatment that nobody can stay on. And when your primary competitor already has incretin drugs with much more tolerable profiles and similar or better efficacy, it is hard to see how this catches up.
The weight loss curve did not flatten out, which suggests there may be more benefit to come over time. But if patients are tapping out at week six because they are vomiting multiple times a day, the rest of that curve does not matter. People are willing to suffer their way to skinny, to some extent, but not when they don’t have to.
This is not just a setback for Amgen. It is a reminder that obesity medicine is not just about the amount of weight lost. It is about how people feel while they are losing it. And right now, MariTide feels awful.
In fairness to Amgen, I have never been real excited about this one, so others may be open to a more even handed run down in MariTide. I’m still a hard pass on this one.
Goes to show how important titration and dosing (always) are:
> Less than a quarter of [MariTide] patients — 22.5% to 24.4% — experienced vomiting with the titrated dosing plans. Drugs that mimic the GLP-1 hormone tend to cause gastrointestinal side effects.
> Without titrating, roughly 65% to 85% of patients reported vomiting, he said.
> "Importantly, nobody dropped out of this trial," Bradner said. "The vast majority of symptoms were quite mild and well-tolerated by patients."
> He said the dosage was titrated over the course of eight weeks. In comparison, other companies have used a six-month titration period, he said.
Vomiting is hugely bad for your dental health, your digestive health, and your mental health, not to mention your quality of life. I just don’t see the point of this drug.