While in Russia the regulation of biomedical cell products (BMCP) area is at the stage of formation, abroad the market of such products is actively developing, and more drugs are coming into practical application. Thus, according to the US FDA, 17 BMCP have already been registered (https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/approved-cellular-and-gene-therapy-products). In the database of the European Agency for the Evaluation of Medicines, information on 16 BMCP can be found, 4 of which applications for registration were withdrawn. (https://www.ema.europa.eu/en/medicines?search_api_views_fulltext=ATMP) It’s worth noting that  additional safety monitoring is being carried out for nine drugs.  At the same time, only four drugs are registered in the USA and in the European Union and are intended for the treatment of oncological diseases (Yescarta, Kite Pharma, Incorporated; Imlygic, Amgen Inc.; Provenge, Dendreon Corporation; Kymriah, Novartis Pharmaceuticals Corporation)

1. Biomedical cell products approved in the USA.

The U.S. Food and Drug Administration (FDA) has approved the use of BMCP for various medical applications. It should be taken into account the fact that in the United States cellular products are combined into one category with genotherapeutic, which, in fact, have no relation to human cells. A brief overview of certified preparations is given in the table below:

№	Trade name	Manufacturer	Active component	Scope of application	BMCP in Russia
1.	Yescarta	Kite Pharma, Incorporated	Genetically modified T cells of the patient	Oncology	Yes
2.	Imlygic	Amgen Inc.	Genetically modified oncolytic viral genetic material	Oncology	No
3.	Provenge	Dendreon Corporation	Autological mononuclear blood cells	Oncology	Yes
4.	ALLOCORD	SSM Cardinal Glennon Children’s Medical Center	Hematopoietic cells, the precursor of umbilical cord blood	Hematology	Yes
5.	CLEVECORD	Cleveland Cord Blood Center
6.	DUCORD	Duke University School of Medicine
7.	HEMACORD	New York Blood Center, Inc.
8.	HPC, Cord Blood	Clinimmune Labs, University of Colorado Cord Blood Bank
9.	HPC, Cord Blood	MD Anderson Cord Blood Bank
10.	HPC, Cord Blood	LifeSouth Community Blood Centers, Inc.
11.	HPC, Cord Blood	Bloodworks
12.	GINTUIT	Organogenesis Incorporated	The culture of allogenic keratinocytes and fibroblasts in bovine collagen	Surgery in oral cavity	Yes
13.	KYMRIAH	Novartis Pharmaceuticals Corporation	Genetically modified autologous T-cells	Oncology	Yes
14.	LAVIV	Fibrocell Technologies, Inc.	Authologic Fibroblasts	Dermatology	Yes
15.	LUXTURNA	Spark Therapeutics, Inc.	Genetic material in the composition of a viral particle	Ophthalmology	No
16.	MACI	Vericel Corporation	Culture of autologous chondroicytes on porcine collagen membrane	Orthopedics	Yes
17.	ZOLGENSMA	AveXis, Inc.	Genetic material in the composition of a viral particle	Pediatrics (treatment of spinal muscular dystrophy)	No

 

2. Biomedical cell products approved in the EU countries.

If we talk about BMCP, which came into circulation in the EU countries, many of them are still under strict control, and some are completely withdrawn either after registration or during it (shown in blue in the table).  Another 32 products are used in EU hospitals as exceptions.

№	Trade name	Manufacturer	Active component	Scope of application	BMCP in Russia
1.	HOLOCLAR	Holostem Terapie Avanzate S.R.L	Culture of epithelial cells of the corneal edge	Ophthalmology	Yes
2.	Spherox	CO.DON AG	Spheroids of human autologous chondroicytes	Orthopedics	Yes
3.	Strimvelis	GlaxoSmithKline	Genetically modified autologous cells CD34 +	Immunology	Yes
4.	Zalmoxis	MolMed SpA	Genetically Modified Allogenic T-Cells	Oncology	Yes
5.	Maci (withdrawn)	Vericel Corporation	The culture of autologous chondroicytes	Orthopedics	Yes
6.	Alofisel	Takeda Pharma A/S	Stem cells of adipose tissue of adult donors	Gastroenterology	Yes
7.	Glybera	uniQure biopharma B.V.	Genetic material in the composition of a viral particle	Gastroenterology	No
8.	Heparesc	Cytonet GmbH KG	Heterological cells of the human liver	Pediatrics (treatment of hereditary diseases)	Yes
9.	Raligize (withdrawn)	Advaxis Inc.	Genetically modified cells Listeria monocytogenes	Oncology	No
10.	OraNera (withdrawn)	CellSeed Europe Ltd.	Authological epithelial cells of the oral mucosa	Ophthalmology	Yes
11.	Hyalograft C autograft (withdrawn)	Anika Therapeutics S.r.l.	Cells of cartilage tissue	Orthopedics	Yes
12.	Cerepro	Ark Therapeutics	Genetically modified virus	Oncology	No

Unfortunately, many of the developed drugs completed their way quickly enough for various reasons. For example, Provenge, intended for the treatment of oncological diseases, could be stored only 18 hours under special conditions, and the cost of treatment when used was $93.000. As a result, these circumstances led to bankruptcy of the manufacturer. MACI, which entered the EU market in 2013 and is intended to restore the cartilage tissue of the knee joint, did not survive the transition period of the manufacturing company associated with the closure of the production site in Europe.

Thus, despite extensive developments in biotechnology and, in particular, BMCP, it is important to note that such preparations need support not only during the development phase, but also at “first steps” in the market.

References:

1. https://www.ema.europa.eu/en/medicines?search_api_views_fulltext=ATMP
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4846788/
3. Eder C, Wild C. Technology forecast: advanced therapies in late clinical research, EMA approval or clinical application via hospital exemption. J Mark Access Health Policy. 2019; 7 (1): 1600939. Published 2019 Apr 19. doi: 10.1080/20016689 .2019.1600939

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©Beawire – June 2019.