Madrigal shares slide despite Phase 2 success
- Madrigal Pharmaceuticals Inc.'s MGL-3196 met its primary and secondary endpoints in a 12-week Phase 2 clinical trial testing the experimental candidate in people with heterozygous familial hypercholesterolemia already on maximal statin therapy.
- MGL-3196 lowered LDL-C by 18.8% in all patients, rising to 21% in patients on an optimal dose and 28.5% in patients who did not tolerate high-intensity statins, the company said. Secondary endpoints included lowering of triglycerides, apolipoprotein B and lipoprotein A.
- Despite the positive topline results, the markets weren't impressed and traded Madrigal shares down nearly 10% by Thursday's close. The company's stock fell another 4% Friday morning.
Madrigal Pharmaceuticals had had a good 2018, with shares climbing nearly 60% from the beginning of the year to Wednesday's close. And so the recent drop may be just a temporary wobble.
It certainly seemed an off-key response to trial results that show statistically significant improvements compared with placebo for both primary and secondary endpoints in a pool of patients who are unable to reach treatment goals.
Wall Street's reaction, though, might be an indicator of the high bar investors hold experimental drugs to in the cholesterol space, given the commercial struggles of several high-profile recent entrants.
MGL-3196, an oral thyroid hormone receptor (THR) β-selective agonist, is aimed at a specific part of a large market. Up to one in 200 people have heterozygous familial hypercholesterolemia, which can lead to early-onset cardiovascular disease. Madrigal's agent is being developed for the 40% of these who cannot reach their LDL-C goals with maximal doses of existing treatments.
Company CEO Paul Friedman noted in a statement that MGL-3196's mechanism of action could be complementary to statins and ezetimibe.
"Results appear to be generally competitive with other oral therapies for LDL including Esperion Therapeutics, Inc.'s bempedoic acid," wrote Evercore ISI analyst Josh Schimmer in a note to investors.
"But we also note a strong signal on triglycerides which supports MGL-3196's potential positioning as a broader metabolic drug. Overall we see this as a win and validating the favorable metabolic profile of MGL-3196."
The Medicines Co. is also taking a shot at the familial hypercholesterolemia market with its RNA interference drug inclisiran, which inhibits PCSK9. Gemphire Therapeutics Inc., meanwhile, has developed gemcabene, though the candidate has been hamstrung somewhat by a higher-than-expected placebo response.
In December 2017, Madrigal's stock shot up by a then 88% on positive results from a Phase 2 trial of MGL-3196 in non-alcoholic steatohepatitis (NASH), an increasingly common fatty liver disorder linked with diabetes and obesity.
- Madrigal Pharmaceuticals Inc. Press release
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