The Return of Thalidomide

The story of Thalidomide is one of the most tragic disasters in drug development history. It was prescribed to pregnant people for morning sickness in the late 1950s and early 1960s, but it caused serious birth defects. After the danger was discovered, thalidomide was pulled from shelves. However, it is still being used today for other conditions, and part of the reason we've resurrected the drug has to do with the same drug testing procedures that it inspired.

Thalidomide is incredibly dangerous during pregnancy, causing at least 10,000 children to be born with severe congenital health problems, and up to 40% of these were fatal. Once thalidomide's connection with birth defects was discovered, most countries banned the drug entirely in 1961 and 1962. One of the legacies of this tragedy is that we realized the need to step up drug safety standards, and all drugs must now be tested for harm to fetuses in at least two types of animals. However, these safety measures make developing new drugs very expensive.

Today, a brand new drug costs a company between hundreds of millions and billions of dollars. This high price tag is why pharmaceutical companies and researchers are so interested in using old drugs for new tricks. Researchers knew about thalidomide's potential for treating other conditions, almost right away. It was found to be an effective treatment for Hansen's disease, which is also known as leprosy. Decades later, it was approved by the FDA and is still used today to treat complications of that disease. Thalidomide has also been shown to be an effective treatment for HIV, lupus, Crohn's disease, and more.

Thalidomide binds to a protein called Cereblon, which plays a vital role in the developing limbs and organs as a fetus grows. But the interaction between thalidomide and this protein also reduces how many inflammatory molecules get produced. In particular, a molecule called TNF-alpha. TNF-alpha is essential for our immune systems, but too much can have negative effects, so regulating it can help treat some diseases like autoimmune conditions. In the 1990s, interest in thalidomide started to really ramp up. In particular, researchers thought maybe it could even help treat cancer.

Thalidomide has another trick up its sleeve. It's called anti-angiogenesis, which means blocking new blood vessels from growing. This can help slow down tumors, but it also has side effects, including potential nerve damage. Despite the tradeoffs, the trials investigating cancer treatment with thalidomide were overall pretty successful, showing that it can work against cancers of the esophagus, kidneys, and pancreas, among others. In 2006 the FDA approved it to treat multiple myeloma, a cancer of the white blood cells.

Despite all this success, thalidomide does still cause birth defects. When it's prescribed, there is a rigorous safety program that comes along with it. In the US, thalidomide is controlled under a Risk Evaluation and Mitigation Strategy, REMS program, by the FDA. This means they verify everyone who gets the drug isn't pregnant already, knows the risks associated, and uses multiple methods of birth control. They also evaluate the risk of medication being mixed up between people in a household, or even being shared inadvertently through intercourse or blood and sperm donations.

Thalidomide can be spread through at least somebody's fluids so even if you personally aren't going to become pregnant, you still need to be careful. The program seems to have worked pretty well. When quizzed about the risk of birth defects, over 98% of patients knew the correct answers. A 2007 study notes that zero new cases of birth defects from thalidomide have been reported in the United States since the drug was approved in 1998! The story of thalidomide is a reminder of the importance of drug safety testing, but also shows that a certain medication might have a crucial role to play in how we treat other illnesses despite its nasty side effects.