Based on those results, U.S. Food and Drug Administration advisers last month recommended approval of lomitapide for the disorder, called homozygous familial hypercholesterolemia - and urged steps to ensure that the drug is not used in lower-risk groups.
An FDA panel member, Edward Gregg of the Centers for Disease Control and Prevention, echoed other advisers, saying that he was concerned about liver toxicity but that the risks were trumped by the condition's severity and the need for treatment options.
The FDA, which usually follows such advice, is expected to decide by year's end.
"For me - and I may be biased - this was truly remarkable, and has the potential to change the course of this disease," said Penn researcher Marina Cuchel, who led the study.
While Penn's achievement should add a much-needed tool to manage the illness, it comes with limitations. Patients must stick to a very low-fat diet, avoid alcohol, take vitamin supplements, and be closely monitored for the most serious side effect: liver toxicity. Gastrointestinal problems such as diarrhea, nausea, and abdominal pain initially bothered almost all patients, and four quit because of the discomforts.
Even if lomitapide were approved, it would be off-limits for children until it was found it to be safe for them.
Children with the genetic disorder are born with staggeringly high cholesterol levels, and often suffer heart attacks by adolescence.
An estimated 6,000 people in the United States and Europe have this inherited form of hypercholesterol production. Conventional cholesterol-lowering drugs such as statins are only marginally helpful. The most effective treatment, a blood-filtering procedure called apheresis that is similar to kidney dialysis, is burdensome and not all patient have access to it.
The 29 patients in the study were on conventional drugs and undergoing apheresis. After six months, three were able to stop apheresis, and three others had it less often.
"If, instead of having apheresis every week, you can go every two or three weeks, it translates to a much better quality of life," Cuchel said.
Study participant Elizabeth Mendez, 48, of South Philadelphia, said that "to finally find something that actually works is a miracle." Diagnosed as a child, Mendez has had three open-chest heart bypass surgeries, the first at age 28. "My cholesterol used to be in the thousands," said the mother of four. "Now it's normal. The drug helped me to be able to stick to my diet. It would be a shame if it doesn't get approved."
That the drug has made it this far is a testament to Penn's researchers, particularly Daniel J. Rader, a leading cholesterol expert. While at a government lab in the 1990s, Rader helped discover the gene responsible for a rare genetic disorder in which patients have extremely low cholesterol.
Bristol Myers Squibb Inc. recognized that inhibiting the gene might reduce cholesterol. Company scientists invented lomitapide - but abandoned development of it because of the bad side effects.
Rader, seeing its potential for patients with the deadly cholesterol disorder, persuaded the pharmaceutical giant to donate the patent to Penn. Ultimately, Aegerion Pharmaceuticals, a Cambridge, Mass., biotech startup, raised millions of dollars for the pivotal human testing of lomitapide.
If it gets to market, Penn stands to collect royalties, while Rader may profit from Aegerion stock. (He was not directly involved with patients in the latest study to avoid potential conflicts.)
One drug industry analyst estimated that lomitapide's annual price tag could be $300,000 a patient, so even though its potential market is tiny, it may pay off.
Rader, who said such a price "wouldn't surprise me," doubts that lomitapide will become more than a niche drug due to the risk-benefit trade-off.
But that niche has a huge need. "This was a tremendous collaboration between Big Pharma, the FDA, the Doris Duke Foundation, and academia," he said. "It's a nice example of how these abandoned drugs can be made available to patients with a fatal disease."
Contact Marie McCullough at 215-854-2720 or firstname.lastname@example.org.