Clinical, regulatory and commercial challenges in rare ......Silvia Stacchiotti...

Clinical, regulatory and commercial

challenges in rare cancers drugs

development:

clinical perspective

Silvia Stacchiotti

silvia.stacchiotti@istitutotumori.mi.it

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

Silvia Stacchiotti

silvia.stacchiotti@istitutotumori.mi.it

OPEN FOR DISCUSSION !