Approval of stem cell therapeutic products is progressing slowly around the world. There are many hurdles in manufacturing, business development and regulation of these highly complex biological products. Today, I’ll look at experience of one particular country – South Korea. This month we have a special event – one year anniversary of the first “stem cell drug” approval on the market!
In the last couple of years S. Korea has achieved a significant progress in development and marketing of stem cell therapy products. Recently, Korea Food and Drug Administration (KFDA) allowed somewhat rapid commercialization track for candidate stem cell products. I think, it’s kind of unique experience, which we can observe and learn from.
A new potential approval, expecting this year: LiverCellgram (FCB PharmiCell).
There is a good number of stem cell clinical trials ongoing in S. Korea. These trials involve all types of stem cells, including embryonic. Recently, CHA Bio & Diostech got an authorization by KFDA for the first embryonic stem cell trial. CHA Bio has a licensing agreement with Advanced Cell Technology and will utilize their ES-derived RPE cells in patients with Stargardt’s Macular Dystrophy.
One of Korean articles (with a link to KFDA as a source) indicates 22 KFD-approved stem cell clinical trials. Out of 22, 13 trials were ongoing and 9 were completed.
The significant part of stem cell clinical trials in Korea is sponsored by companies (industry). In the recent opinion piece, Il-Hoan Oh indicated 15 industry-sponsored (conducted by 6 companies) KFDA-approved stem cell therapeutic trials. You can look at this list here (.pdf)
I’d like to point out some unique features of “stem cell drugs” development in S. Korea:
1. Market approval before release of peer-reviewed data
KFDA made a decision to give a “fast track” for commercial stem cell products through marketing approval. This “experiment” has caused different opinions among experts:
… outside experts worry that the country’s drug agency may be moving too quickly with its regulatory decisions.
Yet, some researchers worry about the efficacy of products of this sort, given the lackluster data released publically to date—and what is known about these agents is mostly through press releases by the KFDA and presentations, not peer-reviewed journals.
There are some worries of Korean experts as well:
Oh of the Catholic University said the lack of independent expert scrutiny and insufficient testing of the treatment’s effectiveness were disappointing for what could otherwise be seen as an indisputable breakthrough.
“Whether the government has done everything in its obligations to be transparent with the public, when it comes to the effectiveness of the treatment, there is some disappointment about that”.
Actually, before approval decision, KFDA had some data for clinical efficacy. For example, Hearticellgram-AMI clinical study included 59 subjects and Cartistem trial – 89. Apparently, these data were not published or reported publicly.
2. Commercialization before completion of clinical trials
So, KFDA allowed the sales of stem cell products before controlled clinical trials were completed. I’m talking about Phase 3. Seem like agency had some clinical data from Phase 2, before approval. Basically KFDA wants to ensure safety of the product at the time of approval, but let market and clinicians demonstrate the efficacy in larger patient population.
3. Bypass of Phase 3?
Even though, first 3 “stem cell drugs” were approved by traditional regulatory path, Il-Hoan Oh brought up the recent proposal for exemption of Phase 3 trials:
… another proposal suggests that stem cell therapeutics from autologous donors should be exempted from phase III clinical trials. Thus, these proposals advocate exemption of phase lll clinical trials to increase the efficiency of industrializing stem cell therapeutics.
He argues against this proposition:
If the efficacies are sub-optimal, patients would be further victimized, by not having medical benefit but having spent money on insufficiently validated cell therapy drugs.
Interestingly, due to expectations from political parties, the industrial sectors in Korea that deal with cell therapeutics are generally opposed to such legislative proposals. The companies are concerned about the possible decline of the credibility of their cell therapy products in international and domestic markets under such conditions, which will hamper their overall market competitiveness.
… further industrial competitiveness for cell therapeutics in Korea should be sought from technological advances and proven therapeutic efficacy of the products rather than from simplification of regulatory systems.
4. Powerful support by a government
Korean government is pumping huge amount of money in stem cell research and products development:
The South Korean health ministry announced last month that research into stem cells and regenerative medicine will receive a funding boost of 33 billion won (US$29 million) in 2012, four times that given in 2011. Overall, six different ministries will invest 100 billion won in stem-cell research this year.
A quote from the Il-Hoan Oh’s opinion piece:
The Korean president described the stem cell field as a “new growth engine” for the nation’s economy. Moreover, legislative movements are being proposed for simplifying the authorization process of cell therapy products in order to lower the barriers against industrialization.
5. Unregulated stem cell treatments are not allowed in Korea
S. Korea is trying to fight with a bogus “stem cell tourism” by prohibition of such treatments:
The KFDA, for its part, stands by its record. Ahn Gwang-soo, deputy director of the agency’s cell and gene therapy products division, points to the strict procedures in place to ensure that medicines are safe and effective. “Although there were some companies that conduct stem cell treatments outside of Korea,” he says, “they are not permitted to administer those treatments within Korea.”
6. A bunch of other cell therapy products on a line
Lee Buckler wrote about specific “Korean experience’:
South Korea is an interesting example of a country with a mature regulatory framework with more than its share of approval. There have been 14 cell therapy products approved for sale in South Korea.
These products were brought to market in 2006-7 under a conditional approval unique to South Korea’s regulation that allows commercial sale in certain instances while a pivotal trial is underway.
Overall, I think, the booming development of stem cell therapeutic drugs in S. Korea is very very interesting. We are going to observe this “Korean experiment” and learn some lessons. In the near future, more data will come on efficacy and market performance of the first 3 approved stem cell drugs.
If you have more information about “Korean boom”, please share in comments!