Clinical, regulatory and commercial challenges in rare ......Silvia Stacchiotti...
Transcript of 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
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ACCESS
to NEW POTENTIALLY
ACTIVE DRUGS
in most EU countries
no access
without EMA approval
(not the same in the US)
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Pharma
Regulators
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Pharma
RegulatorsResearchers
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Pharma
RegulatorsResearchers
Patients
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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
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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
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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
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Not always
– at least with the existing rules –
researcher / patient interest
match
pharma plans
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rarity & time
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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
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Giant cell tumor of the tendon sheat (PVNS)
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Giant cell tumor of the tendon sheat (PVNS)
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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)
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West et al. PNAS 2005
t(1;2) COL6A-CSF1
CSF1CSF1RCSF1R
Autocrine
Chemotaxis
CSF1CSF1R
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West et al. PNAS 2005
t(1;2) COL6A-CSF1
CSF1CSF1RCSF1R
CSF1
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Imatinib 400 mg/day
Giant cell tumor of the tendon sheat (PVNS)
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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)
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0 + 52 mos
Pt 1
IMATINIB x 24 mos
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Suv max 26.9
Suv max 19.3
IMATINIB 400 mg/day
Pt 2
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Nilotinib 800 mg/day
Giant cell tumor of the tendon sheat (PVNS)
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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
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Imatinib licenced for …
GIST > 3/100.000/year
DFSP > 1/100.000/year
CML > 1/1.000.000/year
PVNS lost the momentum
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Pharma
RegulatorsResearchers
Patients
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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
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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”
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Chordoma
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RCE/EMA workshop on Chordoma as a model for
very rare cancers, London 4.201
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Chordoma study end-points, FDA meeting
Chicago 5.2014
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Imatinib
Italy, 648/96