Implanted drug improves tolerance of sunlight in rare condition
WASHINGTON – A skin-darkening drug can help protect against serious pain in people with a rare inherited condition that makes them flee sunlight like movie vampires, according to tests in Europe and the U.S.
The condition, known as erythropoietic protoporphyria, causes severe burning skin pain after several minutes of direct sun exposure. The pain can last for days and sometimes causes redness and swelling. Even bright lights or sunlight coming through a window can trigger it.
Victims sometimes refer to themselves as “shadow hoppers,” said Dr. Manisha Balwani, co-investigator in the U.S. trial.
Adults who received the implanted drug reported that they could spend significantly more time in the sun than those who received a placebo implant, although the increase was not always dramatic because people with the condition have developed a powerful aversion to sunlight that is difficult to overcome.
“In these trials, the biggest improvement is in the quality of life. It made a huge difference,” Balwani, of the Icahn School of Medicine at Mount Sinai Hospital in New York, told Reuters Health.
“It’s a severe condition with extreme photosensitivity, and this is showing the action of a skin-darkening agent that is measurable and significant,” said Dr. David Fisher, chief of dermatology at Massachusetts General Hospital, who was not involved in the research. “It’s a statistically significant but modest change.”
The drug is Clinuvel Pharmaceutical’s afamelanotide, which is sold in Italy and Switzerland under the brand name Scenesse. The company paid for the research.
The drug, given as a grain-sized implant every two months, promotes the growth of pigment-carrying melanin in skin cells. It is approved, but yet to be marketed, in the European Union. It is awaiting approval in the United States. The current cost is E$32,250 per year (US$36,000), according to a company spokesman. No price has been set for when it becomes available throughout Europe, probably later this year.
Clinuvel has yet to develop or test a dose for children, even though the hard-to-diagnose condition typically appears in early childhood. It affects an estimated 5,000 to 10,000 people worldwide.
According to the new results, published in the New England Journal of Medicine, among the 94 U.S. patients, six months of treatment with the drug increased the amount of pain-free time following midday sun exposure by 69.4 hours, compared to 40.8 hours with placebo.
In the European study of 74 patients, nine months of therapy increased the amount of pain-free time to 6 hours, compared to 0.8 hours with the dummy drug.
The exposure times in the two studies are very different because the data were collected differently, said Balwani, and because “the patients have this very ingrained behavior of sun avoidance. It was hard for them to modify their behavior. We never really recognized how deep this behavior was. We feel the effect could have been stronger if these patients had gone out more.”
The number of pain attacks dropped from 146 among volunteers getting placebo to 77 in those receiving afamelanotide.
The researchers also said that when sunlight sparked an attack, it was significantly less severe and recovery time was faster. “The shortened recovery time from phototoxic reactions is a benefit, since these painful reactions can last up to several days and lead to absence from school or work and lost productivity,” the study team writes.
In the European test, afamelanotide recipients logged significant improvement in quality-of-life scores over placebo recipients through the eight-month mark. But at the nine month point, one month after the fifth and final dose, the scores were not significantly different.
In the six-month U.S. test, drug recipients showed the biggest difference over placebo at the second and fourth month, but the quality of life was still better for afamelanotide recipients at day 180.
A second quality of life measure showed no significant change with drug use.
The most common adverse events — all of mild to moderate severity — were nausea, headache, nose and throat irritation and back pain.
“My suspicion is, at the end of the day, because darkly-pigmented humans can still sunburn like crazy, melanin is not like a roof over your head. So it only has a certain amount of efficacy,” Fisher told Reuters Health. “So I’m not shocked that the increase was modest” with the melanin-producing drug.
“But I would love to see further analysis of subpopulations to see where the efficacy would be greater and other populations where it’s not worth the trouble,” he said.
“Most of the patients who got the drug had a very positive response,” Balwani said, so people with the condition “are waiting for the drug. They’re desperate for something to help them lead a more normal life.” – Reuters