Regulatory Open Forum

We have two NMEs in the clinic: compound A and compound B.  Compound A has shown very preliminary efficacy for oncology indication Z, while B has not been tested for that indication.

Preclinical studies suggest that A has efficacy for indication Z, B has almost no activity, while the A+B combo, or A+C combo (where C is an approved medication) work better than A alone.

Indication Z has high unmet medical need, with no approved therapies.  However, there are several single-arm clinical studies from academic groups that show some activities for this disease using marketed drugs, including drug C.  These medications are being used to some extent in clinical practice (off label).

If we use the A+C combo, we will almost certainly need to do a randomized trial to show A+C is advantageous to C alone.  If we use the A+B combo, we might have a shot on accelerated approval (AA) based on single-arm ORR.

• We are unable to find regulatory precedents of AA for a combo of two NMEs. If you know of one, please point us to that example.  If precedent does not exist, is this a risky or unrealistic strategy ?
• When the agency evaluates eligibility for AA, are "available therapies" limited to those that have been approved (e.g. drug C is not considered a treatment option for that indication by the FDA) ?

We have two NMEs in the clinic: compound A and compound B.  Compound A has shown very preliminary efficacy for oncology indication Z, while B has not been tested for that indication.

Preclinical studies suggest that A has efficacy for indication Z, B has almost no activity, while the A+B combo, or A+C combo (where C is an approved medication) work better than A alone.

Indication Z has high unmet medical need, with no approved therapies.  However, there are several single-arm clinical studies from academic groups that show some activities for this disease using marketed drugs, including drug C.  These medications are being used to some extent in clinical practice (off label).

If we use the A+C combo, we will almost certainly need to do a randomized trial to show A+C is advantageous to C alone.  If we use the A+B combo, we might have a shot on accelerated approval (AA) based on single-arm ORR.

• We are unable to find regulatory precedents of AA for a combo of two NMEs. If you know of one, please point us to that example.  If precedent does not exist, is this a risky or unrealistic strategy ?
• When the agency evaluates eligibility for AA, are "available therapies" limited to those that have been approved (e.g. drug C is not considered a treatment option for that indication by the FDA) ?

We have two NMEs in the clinic: compound A and compound B.  Compound A has shown very preliminary efficacy for oncology indication Z, while B has not been tested for that indication.

Preclinical studies suggest that A has efficacy for indication Z, B has almost no activity, while the A+B combo, or A+C combo (where C is an approved medication) work better than A alone.

Indication Z has high unmet medical need, with no approved therapies.  However, there are several single-arm clinical studies from academic groups that show some activities for this disease using marketed drugs, including drug C.  These medications are being used to some extent in clinical practice (off label).

If we use the A+C combo, we will almost certainly need to do a randomized trial to show A+C is advantageous to C alone.  If we use the A+B combo, we might have a shot on accelerated approval (AA) based on single-arm ORR.

• We are unable to find regulatory precedents of AA for a combo of two NMEs. If you know of one, please point us to that example.  If precedent does not exist, is this a risky or unrealistic strategy ?
• When the agency evaluates eligibility for AA, are "available therapies" limited to those that have been approved (e.g. drug C is not considered a treatment option for that indication by the FDA) ?

We have two NMEs in the clinic: compound A and compound B.  Compound A has shown very preliminary efficacy for oncology indication Z, while B has not been tested for that indication.

Preclinical studies suggest that A has efficacy for indication Z, B has almost no activity, while the A+B combo, or A+C combo (where C is an approved medication) work better than A alone.

Indication Z has high unmet medical need, with no approved therapies.  However, there are several single-arm clinical studies from academic groups that show some activities for this disease using marketed drugs, including drug C.  These medications are being used to some extent in clinical practice (off label).

If we use the A+C combo, we will almost certainly need to do a randomized trial to show A+C is advantageous to C alone.  If we use the A+B combo, we might have a shot on accelerated approval (AA) based on single-arm ORR.

• We are unable to find regulatory precedents of AA for a combo of two NMEs. If you know of one, please point us to that example.  If precedent does not exist, is this a risky or unrealistic strategy ?
• When the agency evaluates eligibility for AA, are "available therapies" limited to those that have been approved (e.g. drug C is not considered a treatment option for that indication by the FDA) ?

We have two NMEs in the clinic: compound A and compound B.  Compound A has shown very preliminary efficacy for oncology indication Z, while B has not been tested for that indication.

Preclinical studies suggest that A has efficacy for indication Z, B has almost no activity, while the A+B combo, or A+C combo (where C is an approved medication) work better than A alone.

Indication Z has high unmet medical need, with no approved therapies.  However, there are several single-arm clinical studies from academic groups that show some activities for this disease using marketed drugs, including drug C.  These medications are being used to some extent in clinical practice (off label).

If we use the A+C combo, we will almost certainly need to do a randomized trial to show A+C is advantageous to C alone.  If we use the A+B combo, we might have a shot on accelerated approval (AA) based on single-arm ORR.

• We are unable to find regulatory precedents of AA for a combo of two NMEs. If you know of one, please point us to that example.  If precedent does not exist, is this a risky or unrealistic strategy ?
• When the agency evaluates eligibility for AA, are "available therapies" limited to those that have been approved (e.g. drug C is not considered a treatment option for that indication by the FDA) ?

We have two NMEs in the clinic: compound A and compound B.  Compound A has shown very preliminary efficacy for oncology indication Z, while B has not been tested for that indication.

Preclinical studies suggest that A has efficacy for indication Z, B has almost no activity, while the A+B combo, or A+C combo (where C is an approved medication) work better than A alone.

Indication Z has high unmet medical need, with no approved therapies.  However, there are several single-arm clinical studies from academic groups that show some activities for this disease using marketed drugs, including drug C.  These medications are being used to some extent in clinical practice (off label).

If we use the A+C combo, we will almost certainly need to do a randomized trial to show A+C is advantageous to C alone.  If we use the A+B combo, we might have a shot on accelerated approval (AA) based on single-arm ORR.

• We are unable to find regulatory precedents of AA for a combo of two NMEs. If you know of one, please point us to that example.  If precedent does not exist, is this a risky or unrealistic strategy ?
• When the agency evaluates eligibility for AA, are "available therapies" limited to those that have been approved (e.g. drug C is not considered a treatment option for that indication by the FDA) ?

We have two NMEs in the clinic: compound A and compound B.  Compound A has shown very preliminary efficacy for oncology indication Z, while B has not been tested for that indication.

Preclinical studies suggest that A has efficacy for indication Z, B has almost no activity, while the A+B combo, or A+C combo (where C is an approved medication) work better than A alone.

Indication Z has high unmet medical need, with no approved therapies.  However, there are several single-arm clinical studies from academic groups that show some activities for this disease using marketed drugs, including drug C.  These medications are being used to some extent in clinical practice (off label).

If we use the A+C combo, we will almost certainly need to do a randomized trial to show A+C is advantageous to C alone.  If we use the A+B combo, we might have a shot on accelerated approval (AA) based on single-arm ORR.

• We are unable to find regulatory precedents of AA for a combo of two NMEs. If you know of one, please point us to that example.  If precedent does not exist, is this a risky or unrealistic strategy ?
• When the agency evaluates eligibility for AA, are "available therapies" limited to those that have been approved (e.g. drug C is not considered a treatment option for that indication by the FDA) ?

We have two NMEs in the clinic: compound A and compound B.  Compound A has shown very preliminary efficacy for oncology indication Z, while B has not been tested for that indication.

Preclinical studies suggest that A has efficacy for indication Z, B has almost no activity, while the A+B combo, or A+C combo (where C is an approved medication) work better than A alone.

Indication Z has high unmet medical need, with no approved therapies.  However, there are several single-arm clinical studies from academic groups that show some activities for this disease using marketed drugs, including drug C.  These medications are being used to some extent in clinical practice (off label).

If we use the A+C combo, we will almost certainly need to do a randomized trial to show A+C is advantageous to C alone.  If we use the A+B combo, we might have a shot on accelerated approval (AA) based on single-arm ORR.

• We are unable to find regulatory precedents of AA for a combo of two NMEs. If you know of one, please point us to that example.  If precedent does not exist, is this a risky or unrealistic strategy ?
• When the agency evaluates eligibility for AA, are "available therapies" limited to those that have been approved (e.g. drug C is not considered a treatment option for that indication by the FDA) ?