Regulatory Open Forum

Hi Community Members,
In order to file a Japanese BLA how many (or what % of) subjects from the pivotal trial have to be treated in Japan?
We have completed US recruiting and would like to file for a JBLA but I am pretty sure some portion of the clinical data needs to be based on subjects treated in Japan.

Any insights?

Thank you,

------------------------------
Eugene Helsel
Principal Consultant, Halloran Consulting Group
ehelsel@hallorancg.com
------------------------------

This message was posted by a user wishing to remain anonymous

Not necessarily true to the statement that certain percentage of patients needs to be in pivotal trial in order for you to file JBLA! Before you come to this step, one should have done some early work in Japanese patients and ascertain certain clinical differences, if any, like PK/PD, any safety/response etc that should have given you an idea regarding the composition of subjects in your pivotal trial! From the regulatory & development/clinical Strategy you have several options that you could/should have considered or developed prior to coming to this stage. Have you consulted experienced regulatory consultants who have done pivotal trials involving Japan, China etc????
Original Message:
Sent: 30-Nov-2018 12:30
From: Eugene Helsel
Subject: Clinical trial enrollment in Japan to support JBLA

Hi Community Members,
In order to file a Japanese BLA how many (or what % of) subjects from the pivotal trial have to be treated in Japan?
We have completed US recruiting and would like to file for a JBLA but I am pretty sure some portion of the clinical data needs to be based on subjects treated in Japan.

Any insights?

Thank you,

------------------------------
Eugene Helsel
Principal Consultant, Halloran Consulting Group
ehelsel@hallorancg.com
------------------------------

Interesting response.
We have completed pivotal trial in Japan using the same drug as being used in US trial but different indication, and are filing a JBLA for that indication.
Meeting with PDMA may be best way to determine the extent that Japanese clinical trial data from the prior indication may be used in conjunction with the US clinical trial data to support the JBLA.

------------------------------
Eugene Helsel
Principal Consultant, Halloran Consulting Group
ehelsel@hallorancg.com
------------------------------

Original Message:
Sent: 30-Nov-2018 12:40
From: Anonymous Member
Subject: Clinical trial enrollment in Japan to support JBLA

This message was posted by a user wishing to remain anonymous

Not necessarily true to the statement that certain percentage of patients needs to be in pivotal trial in order for you to file JBLA! Before you come to this step, one should have done some early work in Japanese patients and ascertain certain clinical differences, if any, like PK/PD, any safety/response etc that should have given you an idea regarding the composition of subjects in your pivotal trial! From the regulatory & development/clinical Strategy you have several options that you could/should have considered or developed prior to coming to this stage. Have you consulted experienced regulatory consultants who have done pivotal trials involving Japan, China etc????
Original Message:
Sent: 30-Nov-2018 12:30
From: Eugene Helsel
Subject: Clinical trial enrollment in Japan to support JBLA

Hi Community Members,
In order to file a Japanese BLA how many (or what % of) subjects from the pivotal trial have to be treated in Japan?
We have completed US recruiting and would like to file for a JBLA but I am pretty sure some portion of the clinical data needs to be based on subjects treated in Japan.

Any insights?

Thank you,

------------------------------
Eugene Helsel
Principal Consultant, Halloran Consulting Group
ehelsel@hallorancg.com
------------------------------

I was also confused with your original question just like that Anonymous who responded to your original question.

"We have completed pivotal trial in Japan using the same drug as being used in US trial but different indication, and are filing a JBLA for that indication.
You said "Meeting with PDMA may be best way to determine the extent that Japanese clinical trial data from the prior indication may be used in conjunction with the US clinical trial data to support the JBLA."

From above what I understand is that, basically, you have conducted a pivotal Japanese trial (involving Japanese patients?) for an indication that is different from the US filed indication which was separately supported by US based pivotal trial? i.e. Two separate trials for two separate indications (one for Japanese and one for US?)?

Now you wish to file JBLA for two indications supported by Japanese pivotal trial plus US trial population conducted for the US indication? or just for one Japanese indication with Japanese  pivotal trial patients plus US trial patients from the US trial as a supportive study for safety database?

If you need any help contact us for the above situation. 




------------------------------
GRSAOnline
------------------------------

Original Message:
Sent: 30-Nov-2018 13:21
From: Eugene Helsel
Subject: Clinical trial enrollment in Japan to support JBLA

Interesting response.
We have completed pivotal trial in Japan using the same drug as being used in US trial but different indication, and are filing a JBLA for that indication.
Meeting with PDMA may be best way to determine the extent that Japanese clinical trial data from the prior indication may be used in conjunction with the US clinical trial data to support the JBLA.

------------------------------
Eugene Helsel
Principal Consultant, Halloran Consulting Group
ehelsel@hallorancg.com

Original Message:
Sent: 30-Nov-2018 12:40
From: Anonymous Member
Subject: Clinical trial enrollment in Japan to support JBLA

This message was posted by a user wishing to remain anonymous

Not necessarily true to the statement that certain percentage of patients needs to be in pivotal trial in order for you to file JBLA! Before you come to this step, one should have done some early work in Japanese patients and ascertain certain clinical differences, if any, like PK/PD, any safety/response etc that should have given you an idea regarding the composition of subjects in your pivotal trial! From the regulatory & development/clinical Strategy you have several options that you could/should have considered or developed prior to coming to this stage. Have you consulted experienced regulatory consultants who have done pivotal trials involving Japan, China etc????
Original Message:
Sent: 30-Nov-2018 12:30
From: Eugene Helsel
Subject: Clinical trial enrollment in Japan to support JBLA

Hi Community Members,
In order to file a Japanese BLA how many (or what % of) subjects from the pivotal trial have to be treated in Japan?
We have completed US recruiting and would like to file for a JBLA but I am pretty sure some portion of the clinical data needs to be based on subjects treated in Japan.

Any insights?

Thank you,

------------------------------
Eugene Helsel
Principal Consultant, Halloran Consulting Group
ehelsel@hallorancg.com
------------------------------

Hi Narayan,
Sorry for the confusion. The US and Japanese clinical trials are based on the same drug just different indications
The following statement you made is correct.
"you have conducted a pivotal Japanese trial (involving Japanese patients?) for an indication that is different from the US filed indication which was separately supported by US based pivotal trial? i.e. Two separate trials for two separate indications (one for Japanese and one for US?)"

The Japanese clinical trial is complete and we are developing the JBLA for the indication we studied there. So no issues or concerns there.

The question is:
If we want to pursue a 2nd JBLA for the indication supported by the US clinical trial data do we need additional data from clinical trial subjects in Japan?
I am under the impression that we could not just take our US trial data and use it for a JBLA filing. We would need some data from a Japanese clinical trial to go along with the US clinical trial data.
Is a set requirement for the Japanese clinical trial data needed, given that we have US study data that can be used in the JBLA?

Thanks

------------------------------
Eugene Helsel
Principal Consultant, Halloran Consulting Group
ehelsel@hallorancg.com
------------------------------

Original Message:
Sent: 30-Nov-2018 13:52
From: Narayan Rao
Subject: Clinical trial enrollment in Japan to support JBLA

I was also confused with your original question just like that Anonymous who responded to your original question.

"We have completed pivotal trial in Japan using the same drug as being used in US trial but different indication, and are filing a JBLA for that indication.
You said "Meeting with PDMA may be best way to determine the extent that Japanese clinical trial data from the prior indication may be used in conjunction with the US clinical trial data to support the JBLA."

From above what I understand is that, basically, you have conducted a pivotal Japanese trial (involving Japanese patients?) for an indication that is different from the US filed indication which was separately supported by US based pivotal trial? i.e. Two separate trials for two separate indications (one for Japanese and one for US?)?

Now you wish to file JBLA for two indications supported by Japanese pivotal trial plus US trial population conducted for the US indication? or just for one Japanese indication with Japanese  pivotal trial patients plus US trial patients from the US trial as a supportive study for safety database?

If you need any help contact us for the above situation.




------------------------------
GRSAOnline

Original Message:
Sent: 30-Nov-2018 13:21
From: Eugene Helsel
Subject: Clinical trial enrollment in Japan to support JBLA

Interesting response.
We have completed pivotal trial in Japan using the same drug as being used in US trial but different indication, and are filing a JBLA for that indication.
Meeting with PDMA may be best way to determine the extent that Japanese clinical trial data from the prior indication may be used in conjunction with the US clinical trial data to support the JBLA.

------------------------------
Eugene Helsel
Principal Consultant, Halloran Consulting Group
ehelsel@hallorancg.com

Original Message:
Sent: 30-Nov-2018 12:40
From: Anonymous Member
Subject: Clinical trial enrollment in Japan to support JBLA

This message was posted by a user wishing to remain anonymous

Not necessarily true to the statement that certain percentage of patients needs to be in pivotal trial in order for you to file JBLA! Before you come to this step, one should have done some early work in Japanese patients and ascertain certain clinical differences, if any, like PK/PD, any safety/response etc that should have given you an idea regarding the composition of subjects in your pivotal trial! From the regulatory & development/clinical Strategy you have several options that you could/should have considered or developed prior to coming to this stage. Have you consulted experienced regulatory consultants who have done pivotal trials involving Japan, China etc????
Original Message:
Sent: 30-Nov-2018 12:30
From: Eugene Helsel
Subject: Clinical trial enrollment in Japan to support JBLA

Hi Community Members,
In order to file a Japanese BLA how many (or what % of) subjects from the pivotal trial have to be treated in Japan?
We have completed US recruiting and would like to file for a JBLA but I am pretty sure some portion of the clinical data needs to be based on subjects treated in Japan.

Any insights?

Thank you,

------------------------------
Eugene Helsel
Principal Consultant, Halloran Consulting Group
ehelsel@hallorancg.com
------------------------------

Hi Eugene,

Perfect! Thanks for confirming my understanding of your situation.

Actually, the anonymous respondent above provided a response what needs to be reviewed and assessed prior to submitting JBLA for the US based indication in Japan. You are in a great position to do this assessment. You already have  data from the Japanese patients  from your Japanese trial on this drug. -pk/pd/dose response, dosing schedule/strength etc on this drug-ALTHOUGH in a different indication as well as similar data from the US trial. Your clinician , clin-pharm/biopharm team members should assess this info (i.e. drug/biologic characteristics/behavior between US and Japanese patients), and should be able to decide as to whether or not data from the Japanese patients is required for the US indication JBLA filing in Japan based on this PK/PD modeling. I would recommend that a cross-functional decision needs to be made in this particular situation. With this assessment report included in your proposed JBLA i.e. provided no major differences seen between the US& Japanese subjects with this drug, I would submit the JBLA containing only the US data for the second indication.

Hope this helps!

------------------------------
GRSAOnline
------------------------------

Original Message:
Sent: 30-Nov-2018 15:57
From: Eugene Helsel
Subject: Clinical trial enrollment in Japan to support JBLA

Hi Narayan,
Sorry for the confusion. The US and Japanese clinical trials are based on the same drug just different indications
The following statement you made is correct.
"you have conducted a pivotal Japanese trial (involving Japanese patients?) for an indication that is different from the US filed indication which was separately supported by US based pivotal trial? i.e. Two separate trials for two separate indications (one for Japanese and one for US?)"

The Japanese clinical trial is complete and we are developing the JBLA for the indication we studied there. So no issues or concerns there.

The question is:
If we want to pursue a 2nd JBLA for the indication supported by the US clinical trial data do we need additional data from clinical trial subjects in Japan?
I am under the impression that we could not just take our US trial data and use it for a JBLA filing. We would need some data from a Japanese clinical trial to go along with the US clinical trial data.
Is a set requirement for the Japanese clinical trial data needed, given that we have US study data that can be used in the JBLA?

Thanks

------------------------------
Eugene Helsel
Principal Consultant, Halloran Consulting Group
ehelsel@hallorancg.com

Original Message:
Sent: 30-Nov-2018 13:52
From: Narayan Rao
Subject: Clinical trial enrollment in Japan to support JBLA

I was also confused with your original question just like that Anonymous who responded to your original question.

"We have completed pivotal trial in Japan using the same drug as being used in US trial but different indication, and are filing a JBLA for that indication.
You said "Meeting with PDMA may be best way to determine the extent that Japanese clinical trial data from the prior indication may be used in conjunction with the US clinical trial data to support the JBLA."

From above what I understand is that, basically, you have conducted a pivotal Japanese trial (involving Japanese patients?) for an indication that is different from the US filed indication which was separately supported by US based pivotal trial? i.e. Two separate trials for two separate indications (one for Japanese and one for US?)?

Now you wish to file JBLA for two indications supported by Japanese pivotal trial plus US trial population conducted for the US indication? or just for one Japanese indication with Japanese  pivotal trial patients plus US trial patients from the US trial as a supportive study for safety database?

If you need any help contact us for the above situation.




------------------------------
GRSAOnline

Original Message:
Sent: 30-Nov-2018 13:21
From: Eugene Helsel
Subject: Clinical trial enrollment in Japan to support JBLA

Interesting response.
We have completed pivotal trial in Japan using the same drug as being used in US trial but different indication, and are filing a JBLA for that indication.
Meeting with PDMA may be best way to determine the extent that Japanese clinical trial data from the prior indication may be used in conjunction with the US clinical trial data to support the JBLA.

------------------------------
Eugene Helsel
Principal Consultant, Halloran Consulting Group
ehelsel@hallorancg.com

Original Message:
Sent: 30-Nov-2018 12:40
From: Anonymous Member
Subject: Clinical trial enrollment in Japan to support JBLA

This message was posted by a user wishing to remain anonymous

Not necessarily true to the statement that certain percentage of patients needs to be in pivotal trial in order for you to file JBLA! Before you come to this step, one should have done some early work in Japanese patients and ascertain certain clinical differences, if any, like PK/PD, any safety/response etc that should have given you an idea regarding the composition of subjects in your pivotal trial! From the regulatory & development/clinical Strategy you have several options that you could/should have considered or developed prior to coming to this stage. Have you consulted experienced regulatory consultants who have done pivotal trials involving Japan, China etc????
Original Message:
Sent: 30-Nov-2018 12:30
From: Eugene Helsel
Subject: Clinical trial enrollment in Japan to support JBLA

Hi Community Members,
In order to file a Japanese BLA how many (or what % of) subjects from the pivotal trial have to be treated in Japan?
We have completed US recruiting and would like to file for a JBLA but I am pretty sure some portion of the clinical data needs to be based on subjects treated in Japan.

Any insights?

Thank you,

------------------------------
Eugene Helsel
Principal Consultant, Halloran Consulting Group
ehelsel@hallorancg.com
------------------------------