Derek Lowe's commentary on drug discovery and the pharma industry. An editorially independent blog from the publishers of Science Translational Medicine . All content is Derek’s own, and he does not in any way speak for his employer.

I wrote yesterday about the surprise decision by the Chinese regulators to allow a new Alzheimer’s drug on the market. That drug (GV-971) was developed by Green Valley Pharmaceuticals, a company (and a drug, for that matter) that frankly I had never heard of. But other people have heard of both, and they’ve been contacting me about it. This information warrants a follow-up post.

First off, I mentioned that I was having trouble finding the Phase II data. Well, here’s a summary of it, or at least some of it, and you know what? This compound did not appear to reach statistical significance versus placebo. Not in the trial shown. Why, you wonder, was it progressed to Phase III in the first place? And as mentioned yesterday, it’s not like we have (so far) enough data to evaluate that later trial itself.

However, there is a file going around (especially around Chinese social media), a set of audience photographs (you can see the back of someone’s head in the bottom of the frame) of the presentation given on the drug at the 2019 China BioMed Innovation and Investment Conference, which took place in late September in Suzhou. These slides contain a great deal more information, and some of this was at one point more publicly available on the company’s web site, but seems to have been removed (according to a correspondent of mine this morning).

Here’s a key slide, and the source of that 2.54-point improvement in the ADAS-Cog scores mentioned in the company’s press release. One notable feature is the steep drop in the scores of the placebo group between week 24 and week 36, which is rather strange, and for which no explanation is apparently given. And if I’m interpreting this correctly, both the placebo and treatment groups improved at the earlier time points, it’s just that the treatment group improved more? The same drop in the placebo group is seen in the company’s slide presenting data on the MMSE rating scale. The larger Phase III that’s planned will be of great interest, for sure.

Edit: I want to call attention to this comment, from a researcher in the microbiome field, who has trouble making sense of the recent paper’s data. His opinion is that their results are not consistent with their proposed mechanism of action – I would be very interested in hearing further discussion on this as well!

Moving on to Green Valley itself, AndyBiotech on Twitter has noted that the company has been in regulatory trouble before. This CCTV report from 2007 (there are others) goes into detail (Google Translate needed, unless you’re a Chinese speaker). Their 绿谷灵芝宝 product, Shuangling Guben San (formerly known as Zhonghua Lingzhibao) prepared from the Lingzhi fungus (Ganoderma lucidum, a well-known component of Chinese traditional medicine) has been the subject of many stories in the Chinese press and internet, especially in the 2007-2008 period, but very little of this has ever appeared on the English-language web. It seems to have been marketed (numerous times, over a period of many years) as some sort of cancer cure, with claims on Chinese social media posts such as “It has successfully helped 1.6 million cancer patients in the past 13 years“, which attracted the attention of law enforcement. They’re not the only ones using this ingredient (here’s a Cochrane review on the subject of the fungus, which not surprisingly comes down on the “insufficient evidence” side), but they seem to have been particularly aggressive with their claims and advertising (some sort of proprietary processing that supposedly gave it dramatic potency). This led to lawsuits from patients and customers and exposés in the Chinese media.

If someone more familiar with the history of Green Valley can speak to how what is apparently the same company can now plausibly come forward with an Alzheimer’s drug candidate after such a history, I would be very interested to hear about it. Has there been some sort of major shakeup in management and company behavior? Or are these the same people?

Now for the most recent paper on GV-971. It was noted in the comments section of yesterday’s blog post that its authors have a number of comments in PubPeer on their past work. The paper’s lead author is Meiyu Geng, of the State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, of the Chinese Academy of Sciences. Unfortunately, the comments on other papers from this lab detail what appear to be clear instances of image duplication and overlap in what are supposed to be completely different experiments and samples. There is a lot of that going around, of course, but it’s never right and it’s never a good sign.

So overall, I am even less thrilled than I was yesterday about the prospects for this drug. A new Alzheimer’s therapy is already going to face a tough development path and a lot of skepticism, but this one has even more red flags than I had realized yesterday. More on this as it develops. But it’s not developing well.