1/ A single pill of thalidomide taken during pregnancy can cause major birth defects.
This most notorious drug caused birth deformities in >10000 infants worldwide. It was taken off the market in 1961
But thalidomide never went away. It is sold legally today. How?? The story 👇
This most notorious drug caused birth deformities in >10000 infants worldwide. It was taken off the market in 1961
But thalidomide never went away. It is sold legally today. How?? The story 👇
2/ Thalidomide was first marketed in 1957 as a sedative. By 1960 it was sold in >40 countries. Wrongly touted as the safest sedative for pregnancy.
In 1961 Widukind Lenz and William McBride independently concluded that the drug was teratogenic. It's caused severe birth defects.
In 1961 Widukind Lenz and William McBride independently concluded that the drug was teratogenic. It's caused severe birth defects.
3/ Birth defects occur when even a single pill is taken between days 35-49 of pregnancy.
Thalidomide went off the market in 1961. Due to the wisdom of Dr. Frances Kelsey at the FDA, the drug was never marketed in the US.
Thalidomide went off the market in 1961. Due to the wisdom of Dr. Frances Kelsey at the FDA, the drug was never marketed in the US.
4/ In 1964, Dr. Sheskin in Jerusalem was treating patients with bad leprosy reactions. Just to make patients sleep for a bit, he gave them whatever thalidomide he had.
But amazingly within a few hours these patients recovered dramatically from the leprosy reactions!
But amazingly within a few hours these patients recovered dramatically from the leprosy reactions!
5/ He repeated this a few times and each time the result was equally dramatic. Thalidomide was incredibly effective against bad leprosy immune mediated reactions.
These findings were then confirmed in many trials including a WHO randomized trial.
These findings were then confirmed in many trials including a WHO randomized trial.
6/ Thalidomide was subsequently found to be effective against other immune disorders. So thalidomide lived on.
In the 1990s, thalidomide was found to be effective in the treatment of HIV induced wasting syndrome. An underground market for the drug developed among HIV patients.
In the 1990s, thalidomide was found to be effective in the treatment of HIV induced wasting syndrome. An underground market for the drug developed among HIV patients.
7/ Given the dangers of the drug, the FDA rightly decided that it would be better to market the drug safely in the US with strict precautions rather than the impossible task of stopping illegal distribution that would be hard to track. But data for HIV wasting was not as strong.
8/ So the FDA approved the drug for leprosy (hardly a pressing problem in the US) in 1998, with the recognition that there will be off label use for HIV induced wasting.
The FDA hearing listened to testimony from thalidomide survivors who were now adults with deformities.
The FDA hearing listened to testimony from thalidomide survivors who were now adults with deformities.
9/ In another epic twist of fate, around this time thalidomide was found to be effective for patients with advanced multiple myeloma, a type of blood cancer. This discovery was also serendipitous.
10/ A patient's wife insisted that Dr. Barlogie try the drug for her husband for whom other treatments were not working. Dr. Barlogie listened.
Thalidomide had an effect on the blood supply of cancer cells. Dr. Barlogie discussed with Dr. Folkman and tried the drug on 3 patients
Thalidomide had an effect on the blood supply of cancer cells. Dr. Barlogie discussed with Dr. Folkman and tried the drug on 3 patients
11/ The rest is history. Thalidomide was found to be remarkably effective in 25% of patients with advanced myeloma. Combined with dexamethasone it was effective in over 50% of patients. nejm.org/doi/full/10.10…
12/ I led the randomized trial that led to the FDA approval of thalidomide for myeloma in 2006. The drug helped my career.
Thalidomide and it's cousins lenalidomide & pomalidomide are now used widely for myeloma. There are strict precautions in place to prevent birth defects.
Thalidomide and it's cousins lenalidomide & pomalidomide are now used widely for myeloma. There are strict precautions in place to prevent birth defects.
13/ A few years ago, I met with @MercedesTVACVT from the Thalidomide Victims Association of Canada. Although thalidomide victims worldwide suffered a lot, they have struggled to get compensation. google.com/amp/s/theconve…
14/ I was very moved when @MercedesTVACVT told me that victims understand that the drug that caused so much harm to them was helping other patients live.
15/ If you are interested in more details, check out this article @MayoProceedings @MayoClinic mayoclinicproceedings.org/article/S0025-…
Addendum thats in my paper but I forgot (😳) to include in the thread.
In the early 1960s, astute researchers felt that if thalidomide was powerful enough to cause birth defects it could also have same effect on cancer: 3 clinical trials were done then!! No benefit was found.
In the early 1960s, astute researchers felt that if thalidomide was powerful enough to cause birth defects it could also have same effect on cancer: 3 clinical trials were done then!! No benefit was found.
Their theory before any understanding of the mechanism of action was that if thalidomide affected dividing fetal cells it could have same effect on malignant cancer cells.
They tested the hypotheses in cancer patients. But didn't find benefit.
They tested the hypotheses in cancer patients. But didn't find benefit.
It was not until 30 years later we found that thalidomide indeed had anti cancer properties.
Tells you how you can miss an effect just as serendipitously as you can observe one.
(They even had 3 myeloma patients among the ~300 cancer patients treated in the 1960s)
Tells you how you can miss an effect just as serendipitously as you can observe one.
(They even had 3 myeloma patients among the ~300 cancer patients treated in the 1960s)
In response to a query on mechanisms.
https://twitter.com/vincentrk/status/1371189520142626816
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