clinical, regulatory and commercial challenges in rare ......silvia stacchiotti...
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Clinical, regulatory and commercial
challenges in rare cancers drugs
development:
clinical perspective
Silvia Stacchiotti
ACCESS
to NEW POTENTIALLY
ACTIVE DRUGS
in most EU countries
no access
without EMA approval
(not the same in the US)
Pharma
Regulators
Pharma
RegulatorsResearchers
Pharma
RegulatorsResearchers
Patients
1. Collaboration with Pharma
drug development
initiative to obtain the license of a given medication by
regulators can only be taken by industry (both new and
“old”drugs)
2. Collaboration with Regulators
advise on the characteristics and challenges of a given rare
tumor
Different scenarios:
1. new experimental agents not yet on the market
2. drugs already licenced for other indications
&
❖ preclinical rationale available supporting a try in a
given cancer but no clinical data
❖ clinical data available (retrospective / prospective)
showing clinical activity in a given cancer
Different scenarios:
1. new experimental agents not yet on the market
2. drugs already licenced for other indications
&
❖ preclinical rationale available supporting a try in a
given cancer but no clinical data
❖ clinical data available (retrospective / prospective)
showing clinical activity in a given cancer
Not always
– at least with the existing rules –
researcher / patient interest
match
pharma plans
rarity & time
Different scenarios, an example from true life:
1. new experimental agents not yet on the market
2. drugs already licenced for other indications
&
❖ preclinical data available supporting a try in a new
rare cancer (clinical data not yet available)
❖ clinical data available (retrospective / prospective)
showing clinical activity of a given drug in new rare
indication
Giant cell tumor of the tendon sheat (PVNS)
Giant cell tumor of the tendon sheat (PVNS)
Dal Cin et al, Cencer Res 1994
T(1;2)(p13;q35)CSF1-COL6A3
CSF1 (M-FCS1)
overexpression
Giant cell tumor of the tendon sheat (PVNS)
West et al. PNAS 2005
t(1;2) COL6A-CSF1
CSF1CSF1RCSF1R
Autocrine
Chemotaxis
CSF1CSF1R
West et al. PNAS 2005
t(1;2) COL6A-CSF1
CSF1CSF1RCSF1R
CSF1
Imatinib 400 mg/day
Giant cell tumor of the tendon sheat (PVNS)
Cassier et al, Cancer 2011
# pts: 29, 27 evaluable
retrospective
advanced PVNS
progressive & symptomatic pts
RR RECIST:
1/27 CR
4 /27 PR
20 /27 SD
0/27 PD
median PFS not reached
Giant cell tumor of the tendon sheat (PVNS)
0 + 52 mos
Pt 1
IMATINIB x 24 mos
Suv max 26.9
Suv max 19.3
IMATINIB 400 mg/day
Pt 2
Nilotinib 800 mg/day
Giant cell tumor of the tendon sheat (PVNS)
Blay J et al, Ann Oncol 2008
Still orphan disease
Giant cell tumor of the tendon sheat (PVNS)
High level of disparity in the access
across EU countries
Imatinib licenced for …
GIST > 3/100.000/year
DFSP > 1/100.000/year
CML > 1/1.000.000/year
PVNS lost the momentum
Pharma
RegulatorsResearchers
Patients
We need to promote interaction and discussion among
academia / patients and regulators / payers to:
symplify the requirements and the process needed to
achieve the approval of new drugs in rare / orphan tumors
improve regulators knowledge of a given rare tumor
Adaptive licensing
“a prospectively planned process
by which an early authorization
in a restricted patient population
is followed by iterative phases
of evidence-gathering
and adaption of the marketing authorization
to broader patient populations”
Chordoma
RCE/EMA workshop on Chordoma as a model for
very rare cancers, London 4.201
Chordoma study end-points, FDA meeting
Chicago 5.2014
Imatinib
Italy, 648/96
