New York Washington Seattle Brian J. Malkin, Partner ([email protected]) Brian J. Malkin, Partner...

New York Washington Seattle

Brian J. Malkin, Partner ([email protected])

Frommer Lawrence & Haug LLP

FDA Lawyers Blog

(http://www.fdalawyersblog.com)

INNOVATIVE STRATEGIES FOR NEW DRUG DEVELOPMENTBIOBETTERS

Korea-Maryland, USA Bio Expo 2013November 8, 2013

mailto:[email protected]

©2013 Frommer Lawrence & Haug LLP

KEY TOPICS

· Identifying opportunities to extend into the marketplace.

· Resources necessary for the production of biobetters.

· Assessing the risks and benefits of producing a biobetter.

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WHAT IS A BIOBETTER?

A biological product related to an already-approved biological product but superior in one or more product characteristics.

The term “biobetter” became popular in the context of the Biologics Price Competition and Innovation Act (“the Biosimilars Act”).

Faced with rigorous requirements for biosimilarity and interchangeability in the Biosimilars Act, many applicants have expressed interest in biobetters.

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WHY IS IT “BETTER”?

Product characteristics targeted for improvement Longer product half-life Less frequent dosing Lower likelihood of aggregation Greater efficacy Greater purity Fewer adverse events Streamlined manufacturing Longer shelf-life Easier administration/packaging improvements.

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LEGAL FRAMEWORK

It does not appear that FDA would approve a “biobetter” under the Biosimilars Act. A full BLA is likely required.

The Biosimilars Act does not use the term “biobetter”. The Biosimilars Act authorizes FDA to approve biological

products that are “biosimilar” to an already-approved biological product only under certain circumstances.

“Biosimilar” is defined as• “Highly similar to the reference product notwithstanding minor

differences in clinically inactive components.”• “No clinically meaningful differences between the biological product

and the reference product in terms of safety, purity, and potency.”

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MODIFICATION STRATEGIES

Modification strategies include:

Chemical modification PEGylation Glycosylation New formulation Controlled release New routes of administration (e.g., transdermal, nasal) New manufacturing process Use of new cell platform.

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Some areas of opportunity may include:

Monoclonal antibodies Glycoproteins Vaccines Protein hormones.

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IDENTIFYING OPPORTUNITIES


IDENTIFYING OPPORTUNITIES (cont’d)

· Possible improvements to antibody products · Further humanization

· Minimizing murine sequences and maximizing human sequences

· Increased number of binding targets· Bispecific antibodies

· Antibody-drug conjugates· Links to cytotoxic drugs for targeting to cancer

cells· Antibody fragments

· Smaller versions of full-size marketed antibodies· May provide manufacturing advantages.

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· Possible improvements to glycoprotein products: · PEGylation· Altered glycosylation pattern· Altered amino acid sequence· Fusion with albumin or carrier protein· Use of controlled release technology

· Improvements often focus on improving half-life.

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· Vaccines· Switch from live, attenuated, or inactivated to

recombinant products · Addition of adjuvants· Newer cell culture manufacturing methods· Increasing serotype number (i.e., broader spectrum

of activity). · New delivery methods

· E.g., oral, intranasal, transdermal.

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· Protein hormones· Insulin is a key target.· Much focus remains on modes of administration.

· Orally-administered (e.g., Oramed’s ORMD 0801, Phase II trials).

· Inhaled (e.g., Mannkind’s Afrezza®). · Transdermal.

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· Biobetters require similar resources necessary for the production of biosimilars. · Patent analysis and litigation capabilities· Research and development capabilities· Analytical capabilities · Clinical trial capabilities· Marketing capabilities.

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BIOBETTER RESOURCES


· Benefits· Greater potential to avoid infringing patents or lower

litigation costs.· R&D costs to develop a biobetter may be less than

for developing a new biological product. · “Better” attribute(s) are preferred to the reference

listed product. · Potentially entitled to 12 years of exclusivity under

the Biosimilars Act (FDA request likely required.). · Biosimilars Act suggests more stringent requirements

for biosimilars (especially for interchangeable rating) than biobetters.

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BIOBETTER PROs


· Risks· Sophisticated patent analyses or litigation costs still

may be required. · R&D costs are still high relative to drugs and some

biosimilars. · 12-year exclusivity not guaranteed and no exclusivity

vis-à-vis other biobetters filed as original BLA products.

· Marketing requirements may be high, especially to convert patients from referenced product to biobetter.

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BIOBETTER CONs


QUESTIONS?

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Brian J. Malkin

Partner, Frommer Lawrence & Haug LLP

Editor, FDA Lawyers Blog

202-292-1530 [email protected]

http://www.fdalawyersblog.com

mailto:[email protected]

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