Biosimilar BLA Blah Blah

  • by: |
  • 02/04/2016
From today's edition of Morning Consult:

Tricky Road Ahead For Safe Approval of Biosimilars

On February 9th, the FDA’s Arthritis Advisory Committee will discuss biologics license application (BLA) 125544, for CT-P13, a proposed biosimilar to Janssen Biotech Inc.'s REMICADE (infliximab), submitted by Celltrion, Inc.

If the Adcomm gives a thumbs up and the agency approves the product, this will be the second biosimilar approved in the U.S., but the very first monoclonal antibody, a much more complex molecule than filgrastim.

Apart from the product issues, there are many important policy issues that should be discussed. For example:

Labeling, naming, coding, substitution, non-medical switching and interchangeability are all-important policy issues that FDA has the authority to impact and are appropriate to raise at a high level AdComm.

While extrapolation was allowed for filgrastim, the questions of extrapolation for this product are not as simple or straight forward for the following reasons:

Complexity and Stability

Filgrastim is generally not used as a long-term product for a life-long, chronic disease like infliximab and is much less complex than infliximab, which is nearly eight times larger.  Monoclonal antibodies are used in patients with moderate to severe diseases like Crohn’s or ulcerative colitis and disease stability is critical.  With biosimilar entry the risk of switching the patient to a new, similar product must be carefully considered due to the complexity of the product and disease state.

Regulatory Authorities Split

Because biosimilars are not identical copies of their reference products, even slight differences in structure can affect the biosimilar’s mechanism of action.  Without clinical data in each therapeutic area, it may be challenging to understand the impact of these differences on clinical outcomes.  Infliximab is particularly relevant to the overall conversation regarding indication extrapolation because structural differences have been identified which are thought to be potentially related to the treatment of inflammatory bowel diseases.  The EMA has granted the product full extrapolation including inflammatory bowel diseases, while Health Canada did not, citing uncertainty regarding the clinical impact of observed structural differences. 

Quality Attributes

Biosimilar sponsors compare the structure and function of their products to the reference product using a range of laboratory (i.e., analytical tests) tests.  Because of the complexity and uncertainty with regard to monoclonal antibodies, we can’t always tell which product attributes (or parts of the structure) will be relevant to ultimate clinical outcome and which won’t be.  This is why it’s critical that FDA take a conservative approach and ensure that the biosimilar and reference product are as highly similar as possible, across a wide variety of structural and functional attributes.

Studies Suggest Different Response in Different Disease States

An American College of Rheumatology abstract of infliximab biosimilar data shows difference between adverse events in patients with rheumatoid arthritis (RA) and those with Ankylosing Spondylitis (AS) depending on whether or not they were switched with a 22.5% difference in AS patients that were switched:

* Ankylosing Spondylitis (AS) TEAEs - 48.9% on biosimilar; 71.4% switched from innovator to biosimilar

* Rheumatoid Arthritis (RA) TEAEs – 53.5% on biosimilar; 53.8% switched from innovator to biosimilar.

Pharmacovigilance

Regulatory authorities recognize the importance of robust post-marketing safety monitoring for all drugs including biosimilars.  What make biosimilars different from other drugs however is that unlike generic small molecule medicines where safety can be assumed to be identical as its branded counterpart, a biosimilar is not identical to its reference drug.  Another defining difference with biosimilars is that all biologic medicines may trigger the human immune system to react in undesirable ways such as rendering the medicine ineffective.  Small difference between products may result in different effects on the body’s immune system.   

* Post-marketing safety monitoring is heavily dependent upon voluntary reporting of adverse events by health care professionals and patients.  Unfortunately, this system does not have the capability to effectively monitor and accurately identify adverse events as a result of triggering the body’s immune system.   It is unclear how regulators can or will implement robust ways to compare the safety of a biosimilar to its reference product once approved.

It may be February in Maryland – but the heat is on the FDA. 

CMPI

Center for Medicine in the Public Interest is a nonprofit, non-partisan organization promoting innovative solutions that advance medical progress, reduce health disparities, extend life and make health care more affordable, preventive and patient-centered. CMPI also provides the public, policymakers and the media a reliable source of independent scientific analysis on issues ranging from personalized medicine, food and drug safety, health care reform and comparative effectiveness.

Blog Roll

Alliance for Patient Access Alternative Health Practice
AHRP
Better Health
BigGovHealth
Biotech Blog
BrandweekNRX
CA Medicine man
Cafe Pharma
Campaign for Modern Medicines
Carlat Psychiatry Blog
Clinical Psychology and Psychiatry: A Closer Look
Conservative's Forum
Club For Growth
CNEhealth.org
Diabetes Mine
Disruptive Women
Doctors For Patient Care
Dr. Gov
Drug Channels
DTC Perspectives
eDrugSearch
Envisioning 2.0
EyeOnFDA
FDA Law Blog
Fierce Pharma
fightingdiseases.org
Fresh Air Fund
Furious Seasons
Gooznews
Gel Health News
Hands Off My Health
Health Business Blog
Health Care BS
Health Care for All
Healthy Skepticism
Hooked: Ethics, Medicine, and Pharma
Hugh Hewitt
IgniteBlog
In the Pipeline
In Vivo
Instapundit
Internet Drug News
Jaz'd Healthcare
Jaz'd Pharmaceutical Industry
Jim Edwards' NRx
Kaus Files
KevinMD
Laffer Health Care Report
Little Green Footballs
Med Buzz
Media Research Center
Medrants
More than Medicine
National Review
Neuroethics & Law
Newsbusters
Nurses For Reform
Nurses For Reform Blog
Opinion Journal
Orange Book
PAL
Peter Rost
Pharm Aid
Pharma Blog Review
Pharma Blogsphere
Pharma Marketing Blog
Pharmablogger
Pharmacology Corner
Pharmagossip
Pharmamotion
Pharmalot
Pharmaceutical Business Review
Piper Report
Polipundit
Powerline
Prescription for a Cure
Public Plan Facts
Quackwatch
Real Clear Politics
Remedyhealthcare
Shark Report
Shearlings Got Plowed
StateHouseCall.org
Taking Back America
Terra Sigillata
The Cycle
The Catalyst
The Lonely Conservative
TortsProf
Town Hall
Washington Monthly
World of DTC Marketing
WSJ Health Blog