banter and General Discussion, page-6911

Hi @nippy,

you raise a most important point. Why would Japanese insurers keep 'stumping it up' for Temcell HS Inj. ('Temcell') if it were an "unproven" product?

The answer, of course, is that the Japanese regulatory agencies have already considered Temcell's safety and efficacy and adjudicated it proven. Not just 'potentially able to be' proven. Nor 'likely to be' proven. It's completely 'proven', in the sense that its efficacy has been demonstrated to their satisfaction as for any drug or medical device requiring marketing approval, and those same agencies are happy to allow that approval to continue without further review. That's been the case since 2015.

How can that be, you say? @DocMcstuffins and @whytee deny that Temcell has been 'proven' in Japan.

To these idiots who flounce around pretending to be medical practitioners (with stethoscopes) it is " all very complicated and interesting ". But not 'proven'. They don't substantiate their own opinion with research, but they continue to inflict that opinion on HC:MSB posters and readers, and IMO are misleading all readers quite deliberately in the process. Always keep in mind @DocMcstuffins and @whytee are not mere skeptics - they tell readers every day their unsubstantiated sentiment is to 'Sell MSB'. They don't, & IMO won't, admit it on HC, but they feel they know enough to tell innocent readers their opinion is to sell MSB shares. Who is funding their posts & why they salivate at the thought of dredging up data on Mesoblast's licensed products is an ongoing question.

So, I'll lay out the published facts & hopefully put down this rubbish. Other HC:MSB readers can be the judge.

First, Temcell Hs Inj. is an approved regenerative medicine product in Japan i.e. it's able to be marketed as 'proven'. And here's why:

...and the front page:



Note the highlighted sections, especially the words "..efficacy has been demonstrated". This is a very special decision made by PMDA in relation to Temcell. Ref: https://www.pmda.go.jp/files/000215658.pdf

Well, you might ask, but why is that special? In Japan, doesn't every permitted cell & gene therapy have to demonstrate efficacy to the regulators? The answer is 'No'.

Most therapies permitted by Japan's PMDA for marketing are given a conditional approval & only for a limited time period after which it must be reapplied for after confirmation of efficacy in the post-marketing stage. It's similar in intent to much of the 'Accelerated Approval' pathways used by FDA in the US but the conditions are spelled out up front.

This diagram from PMDA shows how it works:


There are very few approved cell or gene therapies in Japan that have a full conventional (i.e. standard) approval, as for drugs and devices. These products have had to demonstrate to PMDA the long-term collection and evaluation of data that support efficacy. See the Temcell Hs Inj. review report above. Other products, whcih can only demonstrate to PMDA that they are likely to demonstrate efficacy and assure safety can only obtain a conditional approval.

The list of SOPPs that a full approval product has to comply with prior to the approval decision is IMO just as complex and challenging as in the US with the FDA, and arguably more so because the Japanese regulators came to grips with the rapid development of cell and gene therapies before the US, despite the market being so much smaller. Here is an extract:



The entire list of regulations of cell therapy efficacy and safety is too long to print here. See this English language ref: https://www.pmda.go.jp/english/review-services/reviews/0003.html

Also, here's a rough table I put together to show how special the unconditional/ unlimited full Regenerative Medicine Approvals for cell and gene therapies are in Japan.

After 9 years of operation in Japan, there are still only 9 of them, 1 of those 9 being Temcell:

	Approved in Japan	Approved in US	Approx. JP Price (USD) (per treatment)	Approx. US Price (USD) (per treatment)
1	2015 - TEMCELL HS Inj. (JCR Pharm.)	- Available for Mesoblast -	US$99,316	??????
2	2019 – KYMRIAH suspension (Novartis)	2017 - KYMRIAH	US$305,800	US$475,000
3	2020 – ZOLGENSMA (Novartis)	2019 - ZOLGENSMA	US$1,500,000	US$2,100,000
4	2020 – NEPIC tissue (Japan Tissue Eng.)	N/A – autol. cell sheet therapy for LSCD	- - -	- - -
5	2021 – YESCARTA (Daiichi Sankyo)	2017 - YESCARTA	US$243,760	US$373,000
6	2021 -OCURAL (Japan Tissue Eng.)	N/A – autol. cell sheet therapy for LSCD	- - -	- - -
7	2021 – ALOFISEL (Takeda)	- Available for Takeda -	US$40,158	~US$67,000 (not finalised)
8	2021 – SAKRACY (Hirosaki)	N/A – autol. cell sheet therapy for LSCD	- - -	- - -
9	2022 – ABECMA (BMSquibb)	2021 - ABECMA	US$233,300	US$481,499

..and here's the supporting URL: https://www.pmda.go.jp/english/review-services/reviews/approved-information/0002.html

And why would there be no published trial data on the internet?

Well, with competitors like Novartis and BMS around the place, why give them any kind of competitive advantage? Why divulge trade secret information not required to be divulged by the regulator?

Lets not hear any more of this bullshit about Mesoblast Ltd licensee's use of 'unproven' therapies in Japan.

Cheers