(I)
During the epidemic, scientists were trying to solve the problem, and the treatment protocols in China were continuously updated. But at the same time, there are also a lot of “Chinese specialties” and “Chinese specialties research”, such as high level liquor antiviral, soy milk antiviral and so on. In my opinion, the problem with them is not that they are absurd concepts, but that the experimental design is so flawed that they simply cannot prove (or disprove) their conjectures. These kinds of studies are pointless and purely laborious.
I have criticized some of the “specialty therapies” that have no scientific basis but are being promoted in China. For example, CIK cell therapy, which failed in the United States but was used in China for a long time until the Wei Zexi case was stopped.
But readers often question, “Pineapple, I think you’re too superstitious about the United States. Does it mean that what Americans don’t use is not reliable?”
That’s a particularly good question.
In fact, I don’t even care if the therapy comes from America or China, from a Nobel Prize winner or a barefoot doctor, from traditional medicine or modern medicine. I only care about one thing: Is it reliable?
What do you mean by reliable? If you have objective statistics, it’s reliable, and if you have personal experience and intuition, it’s not reliable.
My approach to any therapy is the same:
- If there are no clinical studies to prove objective effectiveness, it should not be mass promoted, much less mass marketed.
- Clinical trials can be conducted for all kinds of therapies, provided they are ethical, but not for a fee. Because once a trial can be charged for, no one cares about the results.
- As long as a therapy is proven to work in clinical trials, even if I didn’t see it before, or I don’t see it, I’ll definitely be the first to support it.
- Fake not knowing, withhold information from patients, and continue to promote it.
- Gather data, look for things to watch out for, and do good research.
Going back to the question at the beginning: if a therapy is not used abroad, does it have to be unreliable?
Of course not! Some drugs may work well in China but not well abroad because of differences between countries. The point is, you have to prove that it really works in China, while trying to figure out why.
(Photo credit: Station Cool Helo)
Today we’ll give you a very classic example from the cancer field.
Erica is a well-known targeted drug that some Chinese patients once called a “miracle drug”: lung cancer patients with a specific mutation may soon have their tumors under control and their symptoms reduced dramatically after taking it orally.
But many people don’t know that this is the same drug that was once killed by the FDA!
The reason is that large scale clinical studies have proven “ineffective”!
The story of the eventual “resurrection” of ERSA is a saga of scientific research with important contributions from Chinese scientists.
(2)
Erica is a targeted drug that inhibits the EGFR protein, and in early trials, it showed some effect in lung cancer patients, with an efficiency rate of about 10%. So in 2003, the FDA granted it “conditional marketing” for the treatment of chemotherapy-resistant non-small cell lung cancer patients.
What does “conditional marketing” mean?
This means that the drug can be marketed and sold first, but large clinical trials have to be done to prove the efficacy of the drug. If it works, we can continue to sell it, and if it doesn’t, we can pull it.
This is a common strategy used by the FDA to balance the need to “get new drugs on the market quickly” with the need to “accidentally approve drugs that don’t work.
But no one expected that the post-marketing study of Erythroxa would actually fail!
The drug company recruited more than 2,000 patients in more than 20 countries around the world and conducted a large double-blind controlled trial of “eresart+chemotherapy” versus “placebo+chemotherapy”.
The result was that the combination of eresart+chemotherapy did not significantly extend the life of patients compared to placebo!
How can an anti-cancer drug claim to be effective if it does not extend life? So, in 2005, Erysal was withdrawn from the US by order ……
To this point, it’s a story very similar to that of CIK biologic therapies: a clinically used approach that was pulled from the market by regulatory authorities because of an inability to objectively prove its efficacy.
But the exciting story of the comeback of Erythropoietin is just beginning. All because there was science and no self-deception.
(iii)
After being pulled from the US, the drug company didn’t give up completely, and by compiling clinical trial data, they discovered something very strange: While the study of Erythronium as a whole didn’t look great, it worked very well on East Asians, especially the Japanese!
For example, in a trial of more than 200 people, with patients from Europe, Australia, South Africa, and Japan participating at the same time, the overall percentage of significant tumor shrinkage was about 18%. But if you analyze it carefully, you find that the response rate was 27.5% for Japanese patients and only 10.4% for non-Japanese patients!
The disparity is striking and cannot be explained by any existing knowledge.
That’s weird!
There are various experts with different opinions and theories flying around, some say it’s a coincidence, some say it’s because the Japanese patients are in better shape with lower doses of chemotherapy, some say the Japanese patients are more female and have different hormones than men, and so on.
While there is no consensus, some believe it and some don’t, there is one objective fact that is irrefutable: Erythropoietin has been repeatedly shown to work well in Japanese patients in multiple clinical trials, significantly better than placebo.
So it has been on the market in Japan and many patients have benefited, even though it was pulled by the FDA in the US.
So, we don’t always have to follow the US, if a drug does prove to be objectively effective in our country, of course it’s available!
The key is “objectively effective”, not simply “I think it works” or “the ancestors have used it for thousands of years, of course it works”.
(Photo credit: Station Cool Helo)
(iv)
Back to the story of Erythromycin. Why does it work differently in different countries?
Interestingly, not only in Japan, but also in other East Asian populations, such as Taiwan and Hong Kong, ERSA works significantly better. Could it be an ethnicity issue?
There’s something even stranger. In Asian populations, ERSA works much better for women than for men! It works far better in non-smoking patients than in smoking patients!
“Asian, female, nonsmoker,” patients with these characteristics not only had higher response rates but longer survival after using ERSA!
The mystery is getting bigger!
Just when everyone was confused, two major scientific discoveries suddenly made a very reasonable explanation for all the weirdness.
East Asian lung cancer patients have a high proportion of mutations in the EGFR gene compared to other ethnic groups. The highest proportion of these patients were women who did not smoke.
Eserisal is particularly effective in killing cancer cells that carry EGFR mutations, while it is almost ineffective against cancer cells that do not have EGFR mutations.
All at once, the clouds were set in motion. It’s not that the drug is ineffective, it’s that it’s not used precisely enough!
Why did the clinical trial in the US fail?
Because the patients who participated were predominantly white, the vast majority smoked, and very few had EGFR mutations, and eresart didn’t work for these people.
So, was the FDA right to stop Eressa in the United States back then? Quite right! Because it prevented more than 90% of patients from using a drug that doesn’t work.
But the type of lung cancer in East Asia is very different, with up to 50% of non-small cell lung cancer patients in China with EGFR mutations, so Erythroxa is highly effective!
To further prove this theory, the famous “Iressa Pan-Asia Study [IPASS]” trial was born. Two Chinese lung cancer researchers, Professors Yilong Wu and Shujin Mo, played an important role in this trial.
1217 lung cancer patients in 9 Asian countries and regions participated in this large phase 3 clinical trial, and the results were striking: the objective response rate with Erythroxel was 71% among lung cancer patients carrying EGFR mutations! And in patients without EGFR mutations, the response rate with ERSA was …… 1%!
71% vs 1%!
So the answer is really quite simple: with the right mutation, ERSA is useful; conversely, ERSA is not useful at all.
Before we understood the relationship between mutations and the efficacy of eresart, it was a matter of luck that clinical trials worked; it was through systematic scientific research that eresart not only overturned the case, but also became one of the classic examples of “precision medicine.
A win-win for both drug companies and patients.
(v)
For a therapy whose efficacy is in doubt, but which the government has not explicitly banned, stakeholders have two options:
Choose the former and you may make a lot of money in the short term; but choose the latter and you may leave your mark on history.
(Photo credit: Station Cool Helo)
At the moment, the epidemic is raging around the world, and Chinese clinical and research workers are playing a very important role on the front lines of the fight against it.
With a lack of effective new drugs, countries are exploring various treatment options. As the country with the earliest outbreak of the virus, we have a huge first-mover advantage in scientific research, a huge opportunity. Respecting patients and respecting science, whether tapping into traditional medicine or relying on modern medicine, Chinese scientists are well positioned to explore a number of specialty therapies that can bring good news to patients.
Chinese characteristics are not the problem; self-deception and lack of ability to dialogue with the foreign research community are. I hope that truly reliable therapies will soon stand out and benefit people from all over the world.