innovation benefits and risks - pearrl

Innovation – Benefits and

Risks

Regulatory Science Symposium – PEARRL Annual Meeting

21st June 2017

Una Moore,

Pharmaceutical Assessment Manager (Acting)

Health Products Regulatory Authority

presented at the PEARRL Regulatory symposium 2017 – for personal use only


Risks

Regulatory Science Symposium – PEARRL Annual Meeting

21st June 2017

Una Moore,

Pharmaceutical Assessment Manager (Acting)

Health Products Regulatory Authority

The contents of this presentation are personal opinions

and are not necessarily representative of the HPRA.


What is Innovation?

21/06/2017 3

Creates

value

Something

new

Brings constant

value to customer’s

business or life

New useful,

bettering

people’s lives

Turning an idea

into a solution

that adds value

Executing an idea -

addresses a specific

challenge and achieves

value for the company

and customer


What is Innovation?

21/06/2017 4

Creates

value

Something

new

Brings constant

value to customer’s

business or life

New, useful,

bettering

people’s lives

Turning an idea

into a solution

that adds value

Executing an idea -

addresses a specific

challenge and achieves

value for the company

and customer



Risks

5presented at the PEARRL Regulatory symposium 2017 – for personal use only

Innovation - Benefits &

Risks

6

1950 - Polio vaccines - live attenuated vaccines (Koprowski).

1953 – Mass vaccination with inactivated vaccine (John Elders, Salk and Sabin)

1963 - Measles vaccine (John

Enders)



Risks

7

1950 - Polio vaccines - live attenuated vaccines (Koprowski).

1953 – mass vaccination with inactivated vaccine (John Elders, Salk and Sabin)

1963 - Measles vaccine (John

Enders)

Vaccination – most effective global

public health intervention after

provision of clean water.


Innovation – Benefits &

Risks

8

• 1955 – polio vaccines contained live virus – 250 cases of polio

• 1955 – 1963 – polio vaccine contaminated with SV40.

• Theoretical cancer risk

• Swine flu pandemic (2009)

• Associated with the H1N1 virus

• Second pandemic withthis virus.



Risks

9


Pandemic declared 11th June 2009presented at the PEARRL Regulatory symposium 2017 – for personal use only


Risks

10


Pandemic declared 11th June 2009

Mortality estimates

Initially 18,000…

Revised to 284,500


Innovation Benefits &

Risks

Biotech Products


Immunogenicity

• Immune responses to therapeutic protein products

may pose problems for both patient safety and

product efficacy.

• Anaphylaxis - can have a fatal outcome unless

treated

• Cytokine release syndrome

• Neutralisation of product

13


Risks



Risks• Cetuximab (Erbitux):

• Chimeric IgG antibody; produced in the mouse cell line Sp2/0

• Indications:

• EGFR receptor expressing colorectal cancer

• Squamous cell cancer of head and neck

• Anaphylaxis in some patients – about 1 to 3%

• Severe anaphylaxis in Southern

U.S as high as 22%



Risks

• Identified that the reaction was IgE-mediated.

• Anaphylaxis due to pre-existing IgE to Galactose-

alpha-1,3-galactose [Alpha-gal]

• Sugar is not found in humans; present on

cetuximab

• How?

• Linked to bites from the Lone

Star Tick


Innovation – Benefits & Risks

TeGenero mAB (TNG1412) trial

• Immunomodulatory drug – treatment of B

cell leukaemia

• CD28 Agonist

• <500 times the dose found safe in non-

human primates

• Phase I studies - Induced severe inflammatory

reactions

• Catastrophic systemic organ failure (cytokine

storm)

16

• Unforeseen biological action in humans - no obvious errors

• Several proposals e.g. Extracellular domain only 96%

homology, lower CD28 expression on the CD4+ memory T-

cells in non-human primates.presented at the PEARRL Regulatory symposium 2017 – for personal use only


Risks

• Advancements in Oncology

• Cancer Immunotherapy – check point targets



Risks

• Cancer Immunotherapies – check point targets



Risks

19

Immunotherapy

PD-L =programmed cell death ligand;

Supresses the immune system -presented at the PEARRL Regulatory symposium 2017 – for personal use only


Risks

20

Immunotherapy

PD-L =programmed cell death ligand;

Supresses the immune system -Sznol M., Chen L., Clin. Cancer Res.

2013; 1021 - 1034


EU Approved Checkpoint

Immunotherapies

21

2011:

Yervoy (Ipilimumab) – advanced melanoma

Binds to the CTLA-4 receptor

2015:

Opdivo (nivolumab) – melanoma, NSCLC, renal carcinoma

and Hodgkin’s lymphoma

Keytruda (Pembrolizumab) - melanoma, NSCLC and

Hodgkin’s lymphoma

Bind to the PD-1 receptor

2016:

Avelumab – indicated for gastric cancer

Binds to the PD-L1 receptor

Additional

Monitoring


Ultra-rare disease

22

Gene therapy

Microbiome therapies

Immunotherapy and

cancer vaccines

Personalised medicine

Drug/device combinations

Gene editing

Veterinary

biologicals

Regenerative medicine


How does HPRA support

Innovation in the Biological Area?


Developing the HPRA

Knowledge Base in Biopharma

24

• HPRA - a centre of excellence within the EU in the

biological/ advanced therapy space

• Why?

• Supporting innovation through assessment

work at the EMA network and preparation of

guidance documents

• Supporting the Biotech industry within Ireland

which is one of Ireland’s major growth

industries

• Providing expert guidance in the area of

biological medicines to Irish healthcare

providers and the Irish public


Developing the HPRA

Knowledge Base in Biopharma

• Established a cross

organisational WG

• Identified areas of existing expertise

• Horizon scanning/liaising other

government organisations –

identified innovative areas of the

future

• Identified what actions required

• Training

• External experts

• What collaborations required with Irish

organisation and other EU agencies

25

Biological

strategy

Compliance

Quality

(Human

and Vet)

PV

Clinical/

Preclinical

(Human

and Vet)


The Biological Strategy

26

ATMPs

Antibody Drug

Conjugates

Botulinum toxins

mAbs

Heparins

Biosimilars

Veterinary

biologicals


Progress to date

• HPRA acting as Rapp/Co-Rapp for new product applications

• HPRA contributing to the assessment of scientific advice

applications

• HPRA acting as Ref-NCA for clinical trials assessments

• HPRA assessed the first heparin biosimilar via Centralised

Procedure

• HPRA takes a lead EU role in assessment of botulinum products

• HPRA assessed the centralised application for the first antibody

for veterinary use

• HPRA is actively involved in revising the EMA clinical trial

guideline ‘Requirements for quality documentation concerning

biological investigational medicinal products in clinical trials’

• HPRA is recognised as expert in assessment of biosimilars


Conclusion

• Innovative technologies - huge benefits

• Safe and timely access to patients

• Benefits > Risks

• HPRA is supporting innovation in the biological

space

• HPRA is planning to extend our assessment

activities into the ATMP (gene, cell and

regenerative therapies)

21/06/2017 28


Risks


21/06/2017 29presented at the PEARRL Regulatory symposium 2017 – for personal use only

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