Biosimilars, Orphan Drugs, Advanced Therapy Medicines:

Current regulatory issues (EU/US)

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“No other sector holds the promise to enhance quality of life, productivity and environmental sustainability through innovation like biotechnology, while also benefitting Europe’s economy and research base”.

Biotechnology at a Glance

Carlo Incerti, Chairman of EuropaBio, 3rd EuropaBio event on the Benefits of Biotechnology, Brussels, 23 June 2015

Biotechnology at a Glance

Presentation Overview

Foci Biotechnology

Orphan Medicinal Products Αdvance Therapy Medicinal Products

Biosimilars

Compliance issues

Biotech Jurisprudence

The Future

Biotechnology at a Glance

RED BIOTECH (or Medical Biotech)

applied to manufactured pharmaceuticals like enzymes, antibiotics and vaccines

and its use for molecular diagnostic

GREEN BIOTECH(or Agricultural Biotech)

applied to agricultural processes or products

BLUE BIOTECH(or Marine Biotech)

applied to marine or aquatic applications

of biotechnology

WHITE BIOTECH(or Industrial Biotech)

applied to industrial or other production processes

BIOTECHNOLOGY

Medical Biotechnology: Why?

350 million patients benefit from direct use of biotech medicine to treat and prevent chronic illnesses- heart attacks, leukemia, diabetes, hepatitis & rare diseases

Healthcare Biotech enables citizens to live healthier, longer lives by providing more medical choices & solutions!

Orphan Medicinal products

Orphan medicinal products - Major developments

1999: “Orphan Regulation” (EC) No 141/2000 on orphan medicinal products introduced incentives for the research, development and marketing of medicinal products for rare diseases2003: “EC’s Communication” on Regulation (EC) No 141/2000 on specific matters involving the designation and market exclusivity provisions of the Orphan Regulation

NEW! 16/11/2015-16/2/2016: EC’s Review Process of the Orphan Regulation (EC) of a Public Consultation with stakeholders“Notice” focusing on the application of Articles 3, 5 and 7 of the Orphan Regulation

Orphan Medicinal products

Significant benefit: clarification of what constitutes a ‘significant benefit’ encouraging the development of orphan products for communicable diseases (e.g. Ebola) reassessment of the orphan criteria for a new subset of the condition when a sponsor extends the use of its product after marketing authorization clarifications on the transfer of orphan designations between sponsors & fair conditions of competition among companies

http://ec.europa.eu/health/human-use/orphan-medicines/developments/index_en.htm

Contributions may be sent by e-mail to:SANTE-PHARMACEUTICALS-D5@ec.europa.eu

Biotechnology & Pioneering role in science

Vinciane Pirard, M.D. Co-Chair EFPIA-EuropaBio Joint Task Force on Orphan Medicines and Rare Diseases

A decade ago, the treatment of CML had been dramatically changed by tyrosine kinase inhibitors (TKIs) Before the introduction of this novel medicine, only 30% percent of CML patients survived to 5 years after diagnosis.

Nowadays the overall survival rate at 5 years is 85%–95%.

http://www.leukemia-net.org/content/home/index_eng.html

Advance Therapy Medicinal products

Advance Therapy Medicinal productsgene therapy for cancer, adult cell stem therapy, or tissue-engineered medicinal products fall under:

Regulation (EC) 1394/2007 provides the overall framework on ATMPs

Tissue Engineering Cell Therapy Gene Therapy

Advance Therapy Medicinal products

http://www.esgct.eu/News-and-Events/News.aspx?ID=10049

Biosimilar products

EMA: A similar biological or 'biosimilar' medicine is a biological medicine that is similar to another biological medicine that has already been authorized for use. Biological medicines are medicines that are made by or derived from a biological source, such as a bacterium or yeast.

EU Guideline, April 30th 2015 Biosimilar: “highly similar to the reference medicinal product in physicochemical and biological terms”

Biosimilars can only be authorized for use once the period of data exclusivity on the original 'reference' biological medicine has expired. In general, this means that the biological reference medicine must have been authorized for at least 10 years (8+2+1) before a similar biological medicine can be made available by another company

FDA: evaluates biosimilar interchangeability ≠

EMA: interchangeability rests with the EU member states

SOS Interchangeability (safety, efficacy & quality): Major Biggest Challenge for Litigation

Biotechnology & Compliance

TRANSPARENCY & BIG DATA: Legal Issues that Biotech companies should address

• Clinical trials will now require stronger legal protection By requiring firms under the new legislation to publish their full clinical trials data as part of the approval procedure, novel indications are often revealed. It can be difficult to patent a further, significant use of the drug at a later date, as the positive new effect has already been made public and is therefore not new or has become obvious.

• Not just Personal Data. Informed Consent

The Personal Genome Project has redefined “informed consent” by requiring a perfect score on a test before participants can even enter their name.Sage Bionetworks, a non-profit organization and Lookout a mobiles security firm have taken a similar approach and present users with interactive policy forms to provide consent.

→ flexibility in designing regulatory exclusivity periods→ strengthening communication and collaboration between the relevant stakeholders

http://www.sciencedaily.com/releases/2015/07/150713095308.htm

Biotechnology & Compliance

Biotechnology complicated legal issues:

-Gaps in Legislation US & Europe-Strong IP protection is essential

The necessary framework to address the issues:

-Robust & predictable regulatory approval system

-Regulatory system matching scientific progress

-EU healthcare need to ensure that effective innovative treatments are approved and reimbursed

Biotechnology & Litigation

CJEU Stem Cell Patents Decision – Brüstle v Greenpeace (C-34/10)

Dr. Oliver Brüstle is a German neuropathologist from the University of Bonn who, in September 1997, successfully applied for a patent regarding the isolation and production of neural precursor cells, as extracted from embryonic stem cells originating from Israel. In 2004, the environmental activist group Greenpeace filed suit challenging the validity of the patent, claiming that because the stem cells extracted by Dr. Brüstle originally came from human embryos, such practice went against notions of ordre public as codified in E.U. and domestic law.

Questions raised regarding the meaning of the Biotech Directive (art.5, 6):-“Human Embryo”: when human body begins to develop?- Use of human embryos for industrial/commercial purposes: exception for scientific research?• Non direct utilisation of human embryos: Materials or ingredients obtained by the prior destruction of human embryos

→ invention non-patentable if any of the necessary steps result to the destruction or is used in the destruction of future embryos…Judging EU Patents’ Morality? ≠ US no such restrictions on stem cell research

Biotechnology & Litigation

CJEU International Stem Cell Corporation vs. Controller General of Patents (C-364/13)

International Stem Cell Corporation, a biotechnology company in Carlsbad, California, challenged the judgement after an application it made in the United Kingdom for two patents was rejected. The patents covered methods to generate corneal tissue from ES cells that had been made from egg cells, or ova, through parthenogenesis.

International Stem Cell, however, uses processes based on unfertilized human eggs.

EU Court: An organism which is incapable of developing into a human being does not constitute a human embryo within the meaning of the Biotech Directive. Accordingly, uses of such an organism for industrial or commercial purposes may, as a rule, be patented!

Pending Bioethical questions…

Biotechnology: Our FUTURE

Fascinating news…

In 2013 the US Food and Drug Administration (FDA) ordered 23andMe to discontinue marketing its personal genome service (PGS) as the company had not obtained the legally required regulatory approval resulting in concerns about the potential consequences of customers receiving inaccurate health results. The company continued to sell a personal genome test without health-related results in the United States until October 21, 2015, when it announced that it would be including a revised health component with FDA approval.Based on a sample of saliva, the health-related service will now offer carrier data for 36 genetic diseases, such as sickle cell anemia and cystic fibrosis, ancestry information, and predisposition tests to wellness and trait characteristics. It will not, however, indicate whether a person may have adverse reactions to certain drugs or test for common conditions– including breast and ovarian cancer, Alzheimer's and heart disease – like the company's previous offering.

BREAKTHROUGHS in the LAB are driving BIG RETURNS

The Nasdaq Biotechnology index has nearly quintupled over the past decade and returned 34% last year alone,easily eclipsing the S&P 500’s gain of 11% for 2014.