Introduction to Drug Development in
Commercializing Biomedical Technology
May 13, 2015
Jeffrey Larson, Ph.D., DABT
“Turning Your Research Into A Therapeutic
What You Should Think About and When"
Summary
• FDA Exclusivity – How does exclusivity differ from
your patent?
• Development works BACKWARDS from the label
• Your first step – the Investigational New Drug (IND)
submission
FDA Exclusivity
• Patent protection is not the same as FDA exclusivity
• New Chemical Entity (NCE) exclusivity is 5 years
– Exclusivity is around the moiety itself and not the indication
– Other companies cannot pursue other indications
– Competition cannot file ANDA until 5 yr is up (so essentially 7
yr)
– Risk is that another company can file an NDA if they
generate their own clinical data
• Clinical Investigation (CI) exclusivity is 3 years
– New dosage form, new indication, OTC switch
– Exclusivity is specific to indication
– Competition can file ANDA during exclusivity period
FDA Exclusivity
• Orphan Drug exclusivity is 7 years
– 200,000 or fewer patients
– Exclusivity is around the indication, FDA may approve
another company’s NDA for a different indication
– FDA may accept another NDA for the same drug
substance if drug product is clinically superior
• Pediatric exclusivity can add 6 months
– 6 months to all exclusivity
– FDA must first request Sponsor to conduct pediatric trial
I
d
e
a
How much
time is
remaining on
your patent?
Patent
Prosecution
FDA Review
Patent Issues
Expires
Preclinical
Start 0 yrs 3 yr
Market
Exclusivity
Clinical
4.4 yr
14 yr
16 yr
20 yr
Prior Art
• Prior art - information made available to the public in
any form before the date a patent is claimed
• If an invention is described in the prior art, a patent
on that invention is not valid
• “I have done groundbreaking work for this DRUG in a
wildly novel indication. Why isn’t pharma
interested?”
• If the work is prior art on a known NCE, the only scenario
available is a 3 yr FDA exclusivity
• Likely cannot make money to cover the cost of clinical
development
Path to Drug Development
•
My therapeutic kills cancer cells
• Throw my drug on cells and they stop dividing
• IP dose my drug and tumor shrinks
•
•
•
•
Do my preclinical tox/PK
Make my drug GMP
Run clinical trials
Get FDA blessing to sell and make some money!
Working Backwards?
•I just know it kills cancer cells, not
what the label will be! But:
– What is the treatment schedule?
– Neoadjuvant, adjuvant or metastatic
disease?
– First line, second line, fourth line?
– Instead of or on top of standard of care?
– Can you enroll patients in clinical trials?
– Is cost of goods reasonable?
– Reimbursement – can I get
reimbursement and for what indications?
The Patient Population to Whom You
Market the Drug Drives Clinical
Development
• Patient Population
Can you enroll your trial?
– Single agent or combination?
– Treatment of disease or
prevention of disease?
– Treatment and duration?
– Third line and then move up
to first line?
– Enroll all comers to targeted
patient population?
– Biomarker for patient
selection?
What you intend to do in the Clinic
and Marketing Drives Manufacturing
Development
• CMC (Chemistry, Manufacturing &
Controls)
– Can I scale-up the research process to
amounts anticipated commercially?
– Is the drug substance and drug
product stable to meet clinical
expectations?
– What does a formulation look like?
– How am I going to use the drug – how
do I see it being prescribed and how
does it come from the pharmacy?
Preclinical Toxicology and PK
•Goals:
– Identify/characterize target
organ toxicities
– Maximum Tolerated Dose
(MTD), No Observable Effect
Level (NOEL) & Lowest
Observable Effect Level (LOEL)
– Assess time to toxicity and reversibility of effects
– At what blood levels (tissue levels) are toxicities observed
– Do systemic exposures vary with number of doses?
•Characterize toxicity profile in animals and not
humans!
What You Intend to do in the Clinic
Drives Preclinical Development
• Preclinical Toxicology and PK
– Determine appropriate species
dependent on drug/biologic
– Treatment duration and regimen
determines what the toxicology
program looks like
• How often and how long?
– Treatment indication determines what
toxicology program looks like
• Genotoxicity, reproductive toxicology
– Route and excipients
To sum, studies are not conducted in a vacuum
What You Intend to do in the Clinic
Drives Pharmacology Development
• What is the appropriate species?
• How can I build value?
– What is the dose? What is the route? How often and for
how long? Would the regimen translate into the clinic?
– Can I focus on a particular indication?
– Is there a biomarker I can use to tell the drug has reached
the site of action at the required concentration and is
doing what I intend for it to do?
• How high should I set the bar for positive results?
Again, studies are conducted to inform the clinical
team about how to use the drug and in which patient
Other Issues in Pharmacology
Development
• There is no guidance on the number of studies that
you have to conduct – you have to generate data
that convinces FDA to allow you to put people at
risk
• Studies do not have to be GLP, but I always
recommend in the “spirit of GLP” with regards to
record keeping and reporting
– You are going to have to report data to FDA at some point
– Characterize the drug to the best of your current
knowledge, including formulation
Investigational New Drug
Application (IND)
• The document is a request from the
company/investigator to the FDA to administer an
investigational drug to people for a particular
indication
• Essential Components
– Results of preclinical efficacy, PK and toxicology
– CMC: Information on composition, manufacturing and
quality control
– Clinical study protocol for your human trial
• INDs are either commercial or research
Investigational New Drug
Application (IND)
• You need to provide sufficient efficacy data to
convince FDA that the drug will work
– Data can be your data and/or data from the literature
– Include mechanistic data showing that the target is in the
disease pathway; POC data does not have to be only with
your compound
• You need to convince FDA that drug is reasonably
safe at the intended clinical use
– Risk: benefit profile will depend on disease being treated
– Data on analogous compounds also important for class
effects
Investigational New Drug
Application (IND)
• The FDA has 30 days in which to act on an IND
submission
• No news is good news, OK to proceed
• If FDA doesn’t like something, they can slap a
partial or complete clinical hold
•A clinical hold could be avoided by having first
had a pre-IND meeting to discuss potential issues
with FDA
An Informative Pre-IND Meeting is
critical for a Successful IND Submission
• FDA wants you to succeed
• FDA is willing to provide
guidance on the data that
you need to submit to
support your IND
•Meeting may be in person
or via teleconference (if at
all) – and you only get ONE
•Asking the right questions is
key
Pre-IND Meeting – On what issues do
you want FDA concurrence?
• Pharmacology
– Do the pharmacology studies support the intended
clinical regimen?
• Toxicology
– Do the proposed GLP toxicology studies support the
proposed clinical trial
– Species, dose levels, dose regimen, dose duration?
• CMC
– We are changing xxx for the clinical GMP production, will
the drug substance produced by yyy and tested in GLP
toxicology studies support the proposed clinical trial?
Pre-IND Meeting – On what issues do
you want FDA concurrence?
• Clinical
– Does FDA concur with the first clinical trial in the intended
disease population?
– Does FDA concur with the proposal to enroll patients on
investigational drug alone?
– Does the Agency agree with the time (duration) between
enrolling and dosing individuals within a cohort?
– Does the Agency agree in the proposal to enroll patients
in the first two cohorts on investigational drug alone and
the subsequent cohorts on drug plus standard of care?
– Does FDA agree with the primary endpoint in the Phase 2
trial?
Pre-IND Meeting – What to Expect
• You may obtain concurrence on all issues and have no pre-
IND meeting, or they will be a teleconference or you may be
invited to in person meeting
• The Sponsor (you) will have a team of all relevant players and
FDA will have a team of relevant players
•Generally an hour is the time allotted for the entire meeting
• No visual presentation– you will have provided a detailed preIND meeting package – you get straight to the questions
• Don’t ask open ended questions and have back-up strategies
•You keep minutes and FDA issues draft minutes on which you
can comment. Final minutes are issued by FDA.
Recommendations are not absolutely binding, but very
unusual for FDA not to be bound by their recommendations
Summary
Protect your IP !!!
Loose lips sink ships
Development of target product
profile is essential for early
development.
Discussions with FDA early and as
often as necessary are crucial
Contact:
Jeffrey.larson@texasbioalliance.org
6500 Main Street, #1040
Houston, TX 77030
713-979-9107
Empowering Innovation In Life Sciences