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China’s First Homegrown Pharma

The Wall Street Journal had an article on a new HDAC inhibitor from Shenzhen Chipscreen (full text here from The Australian). It’s worth highlighting. Epidaza (chidamide) appears to be the first homegrown drug discovery and development effort to reach regulatory approval in China.
Their founder, Xian-Ping Lu, was working at Galderma before he went back to China in the early 2000s to start his own company. Chidamide is a start-to-finish compound for Chipscreen, and that puts China on a rather short list of countries that have demonstrated the ability to do that in small molecule drug development. You see claims for this sort of thing that don’t quite hold up, but this certainly appears to be the real thing, and congratulations to them.
Some thoughts: first off, this would be the fourth (I think) histone deacetylase inhibitor to get regulatory approval somewhere. That class of compounds was a hot topic for development ten or twelve years ago (I was working on some then, not to any great effect). It’s the first class of pharmacological agents deliberately targeting epigenetic signaling, and the complexities of that field have made things run slower than people were hoping. As this article in Nature Reviews Drug Discovery put it:

Oncology drug developers have long been interested in the role of HDACs, which can repress gene transcription by modulating chromatin structure, because altered expression of HDAC enzymes is often seen in tumours. HDAC inhibitors, the researchers hoped, could drive the re-expression of silenced genes, including those that encode tumour-suppressing proteins. However, the failure of multiple HDAC inhibitors to show activity in most cancer types, especially in solid tumours, has over the years led to an outbreak of ‘HDAC inhibitor fatigue’ in the research community — distinct from the physical fatigue many patients experience as a common side-effect of the drugs. “The wave of excitement surrounding this early class of epigenetic drugs has waned and been replaced by a wave of scepticism,” says Jean-Pierre Issa of Temple University in Philadelphia, Pennsylvania, USA, who researches epigenetic mechanisms in cancer.

As these mechanisms get more worked out, the hope is that the HDAC compounds can get on a more sound footing, but for now, they’re minor players in the oncology world. (I have no feel for how well chidamide compares to the other marketed compounds).
The second thought is whether Chipscreen plans to seek approval to market the drug anywhere outside China. I hope so – it would be good for Chipscreen and good for the global reputation of the Chinese drug industry. What would be good is if China becomes another market like the US, EU and Japan, where companies from each region get drugs approved in the others. There are (or can be) some slightly different requirements in each, and sometimes regulatory authorities will let something through in one that doesn’t fly in the others, but the serious drugs end up in all of them and other markets (Canada, South America, Australia, Israel and so on) besides. (I’m excluding some of the no-efficacy-just-safety compounds from Japan from that category). What China does not need is to become a sort of regulatory backwater. The sheer size of the market there argues against that happening, but if the drug industry there continues to develop, the government could conceivably start tipping the scales towards China-discovered compounds. Getting chidamide out into the rest of the world would help to get things off to a good start.
The last thought comes from the statement in the article that the drug cost about $70 million to develop. That is indeed cheap, as little as ten per cent of what it would cost to do that in the US or the EU. And why is that? One’s first thought is cost of labor, but although it can be cheaper to outsource some parts of drug research to China, it does not save you 90% by any means. Most of the money spent in a drug project is spent in the clinic, so my guess is that Chipscreen was able to get their clinical trials done for much less money than it would cost over here. Just how and where those savings came in, though, I couldn’t tell you. If that’s a real effect, though, and if those are real figures, then the Chinese companies would appear to have a huge cost advantage on the rest of their worldwide competition, which makes you wonder why it’s taken until 2015 for the first locally-produced small molecule to show up. I should note as well that the other big multinational drug companies have not swarmed into the Chinese clinical trial space, not to the degree you’d expect if there were really 90% savings to be realized by doing so. This part will remain an open question for now.
But all of that aside, I’m glad to see Chipscreen make it through with their own compound. I’m glad to see any small company do that, Chinese or not, but their position as the first to do it in China is something that no one can take away from them. People have been waiting for it to happen, and here it is.

25 comments on “China’s First Homegrown Pharma”

  1. Vanzetti says:

    The real question here, are USA and EU going to trust any clinical trial results from a country that harvests organs from executed criminals?

  2. Mike P says:

    If the $70 million dollar figure is correct, it probably means that the amount (and/or quality) of clinical study necessary to get approval in China is significantly less than what they would need to get the same drug approved in the EU or US.

  3. TX raven says:

    Are the files used in the “NDA” open to the public?
    If so, what’s the website address?
    Thank you.

  4. diver dude says:

    From personal experience, I can report that managing clinical studies in China is “different” to the EU/US in a major way. You had better be very familiar with your company anti-corruption guidelines and I suspect being “home grown” gives you a huge advantage both from the point of view of knowing how things work and that your face fits politically. I doubt these claimed cost savings would accrue to a western company doing equivalent work.

  5. CMCguy says:

    I would surmise the low cost of drug development for the Chinese market actually was beneficial in helping overcoming “HDAC inhibitor fatigue” since the normal cost is so high in Westernized Regions the majority of projects that encounter a hint of risk get rapidly squashed before can mature enough to even attempt to answer efficacy in real world (even if might be a me-too).
    At the same time China will likely remain a regulatory back water from the global perception unless they can truly adopt and enforce cGXP standards that are meaningful. I have observed products that met Chinese GMP that was quite scary to review, both from quality control and facility safety/environmental operations. I recognize improvements have been made in recent times but the general system on a whole appears to have an entrenched corruption and intentional “buyer beware” philosophy that means trust is fleeting.

  6. Barry says:

    “start-to-finish” is a big claim, maybe more than is warranted here. HDAC was already a validated target and the assays were published. Sure, that’s where Med. Chem. begins. But it’s not where a drug-discovery effort starts

  7. Stuart says:

    Are there more countries that have developed a nuclear weapon than have developed an approved small molecule? What does that say about the relative difficulties of doing so?

  8. Anon3 says:

    I hope this does turn out to be a good drug with many useful indications, and congratulations to this company if that is the case.
    Separately, how might they react if the US or India was to compulsory license this new drug? I think it would be interesting to see how their government would respond to the tables being turned.

  9. bradpalm1 says:

    Merck, at least, is not currently suffering from ‘HDAC inhibitor fatigue’ with their recent collaboration with Syndax to study the combination of entinostat, a selective HDAC inhibitor, with their PD-1 inhibitor pembrolizumab (Keytruda). In many studies both selective and non-selective HDAC inhibitors may augment PD-L1 expression on different tumor cells and potentiate the combined effect when used with checkpoint blockade. Presumably companies with these checkpoint inhibitors are looking at novel ways to increase the immunogenicity of non-immunogenic cancers such as lung, breast, prostate and pancreas to expand the their role beyond melanoma.

  10. Mike P says:

    Sadly, I’m sure that would have more to do with priorities than with difficulty.

  11. Anonymous says:

    Are there more countries that have developed a nuclear weapon than have developed an approved small molecule? What does that say about the relative difficulties of doing so?
    10 states have developed nuclear weapons: USA, USSR, France, UK, China, India, Israel, South Africa*, Pakistan, North Korea.
    Approved small molecules: USA, UK, France, Switzerland, Germany, Israel, Sweden, Denmark, Japan, China, Netherlands,
    Belgium, Mexico, Italy, Canada… no doubt I am missing others.
    I was sure that I had read of *some* drug or other discovered in the USSR that eventually made its way to the West but I could not actually find a confirming citation with a few minutes of searching. It seems surprising considering the Soviet strength in other pure and applied sciences (e.g. mathematics and aerospace).
    *Weapons later relinquished

  12. milkshake says:

    @11: azithromycin (Zitromax) was developed in Jugoslavia in 70s and 80s, Pfizer licensed it and made a fortune on it.
    Tegafur (aka Ftorafur) comes from USSR
    Tenofovir, Adefovir and Cidofovir come from work done in Czechoslovakia in 70s and 80s, although the final prodruging was done in Belgium. Gilead made fortune from these drugs.

  13. David says:

    @11: Do you really think that list of nuclear countries is limited by technical ability? Do you seriously think that Japan, Germany, South Korea, etc. couldn’t make nukes if they wanted to? There’s a lack of desire and effort that seems unlikely to be missing in the drug development sector.

  14. Matt says:

    @13: I was only attempting to answer the question about whether more countries had developed small molecule drugs or nuclear weapons. I was accidentally anonymous at the time.
    South Africa developed its weapons on a shoestring budget of only ~$10 million per year (not adjusted for inflation). Obviously many countries have the industrial and budgetary resources to develop nuclear weapons but have declined to do so for other reasons.

  15. Candy Ton says:

    I would rather focus on the fonuder. Except for Xian-Ping Lu, China does have other excellent pharmacists.

  16. schinderhannes says:

    Germany has contributed quite a lot to finding new drugs (like sulfonamides in the late 1930s), but luckily never had a nuclear weapon.

  17. anchor says:

    @12-As a matter of fact Zithromax (Azithromycin) was made by Pliva Pharmaceuticals (Croatia). Your point well taken!

  18. anonymous says:

    @ 11 _ Pakistan and North Korea never had a publication in the scientific journal but are a Nuclear Power because of China and pilfering/stolen technology from the Europe (AQK), especially from Netherland!
    @16_Germany paved for many technology that enabled others to produce the nuclear weapon! But was forced to “clamp down.”

  19. Anonymous says:

    @8: I am curious – what if Chipscreen does not go for approval in India, then India probably cannot compulsory license the use? What benefit does the company have in bringing a drug to a market where they fear it will be “given away”?

  20. steve says:

    Iran/Iraq – At least the first evidence of beer is from that area so if you count alcohol as a small molecule drug then they win the award for first

  21. steve says:

    Woops – sorry; posted in the wrong thread

  22. Hap says:

    I am guessing that if it’s not patented there, then companies in India can make and sell it within the country as they wish – they just can’t sell it (legally) outside the country (in one of the other places covered by its patenting). I assume if they couldn’t get the drug in India, that that might also trigger legal exceptions to make it for internal (cough) use.

  23. Anonymous says:

    This is not the first start-to-finish drugs approved in china. I can think of at three others, one of which was a COX2 inhibitor approved in 2011 I believe

  24. anonymous says:

    @13–that’s true if you replace “lack of desire” with “international treaties compelling them not to and an overwhelming American military presence which reinforces the status quo and removes their utility.”
    Don’t act like Germany, Japan and S Korea have some huge moral high ground, here. Yes, anyone thinking about it would conclude that they could each create a nuclear weapon as quickly as they wanted to.

  25. Mfernflower says:

    It’s structure reminds me alot of capsaicin, Wonder if it has any COX inhibitor action or has a spicy feel in the mouth?

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