WEBVTT
00:00:01.229 --> 00:00:19.960
Bringing a novel therapeutic to market is an art Hear VAs stat thought leaders as they draw on their specialized expertise to offer insight on timely, relevant topics that impact clinical development, the regulatory landscape, and patient access to these novel therapies.
00:00:20.969 --> 00:00:28.879
Hi everyone, and welcome to Art Podcasts, Advancing Revolutionary Therapies, a podcast series presented by the Centers of Excellence at Vata.
00:00:29.250 --> 00:00:30.559
My name is Mara Hollinger.
00:00:30.560 --> 00:00:49.158
I'm the Senior Vice President of regulatory affairs here at Vata, and I'm delighted to kick off season three, a dedicated series of regulatory podcasts on topics that cover everything from smart regulatory strategies to maintaining continued regulatory compliance to the influence of health authorities on clinical trials and more.
00:00:49.719 --> 00:01:04.319
Today I'm joined by Alexis Northcutt, regulatory strategist and Ellen Truitt, associate regulatory strategist, both also with Baratt to discuss today's topics on orphan drug designation and specifically orphan subsets.
00:01:04.650 --> 00:01:06.560
So welcome Alexis and Allen.
00:01:06.561 --> 00:01:07.959
Thank you for joining today.
00:01:08.319 --> 00:01:09.319
Thank you, Mara.
00:01:09.319 --> 00:01:10.439
Happy to be here today.
00:01:10.590 --> 00:01:11.719
Yeah, thanks Mara.
00:01:11.721 --> 00:01:12.239
Me as well.
00:01:12.909 --> 00:01:19.000
Okay, I'm going to hand it right over to you, Alexis, to just explain in general what the Orphan Drug Designation Program is.
00:01:19.840 --> 00:01:20.329
Sure.
00:01:20.459 --> 00:01:32.489
So FDA's Orphan Drug Designation Program, which you will hear us referring to as O D D, is meant to provide incentives and support to encourage the development of treatment for rare diseases.
00:01:32.780 --> 00:01:47.930
So I don't think there's any argument that there have been incredible medical and scientific advances throughout the 20th and into the 21st centuries, but at some point in the seventies and eighties we began to realize that we were neglecting this smaller population of patients whose diseases just weren't that common.
00:01:48.500 --> 00:01:58.290
So this program gives FDA the authority to grant orphan drug status to a drug or a biologic that prevents diagnosis or treats an orphan or a rare disease.
00:01:58.620 --> 00:02:09.490
So some of these incentives that are included with this orphan drug designation are exemption of from user fees, potential for seven years of marketing exclusivity and tax credits for some clinical trials.
00:02:10.219 --> 00:02:11.319
And this is Ellen.
00:02:11.590 --> 00:02:19.479
I also wanted to add, you know, in order to be eligible for this designation, the disease must afflict less than 200,000 people in the us.
00:02:19.740 --> 00:02:32.680
One of the most common questions we get from sponsors seeking O D D is whether their population is appropriate, and in some cases, whether a chosen disease subgroup could be suitable for a successful O D D request.
00:02:33.560 --> 00:02:39.560
Ellen, could you expand on what would make a subgroup of a disease suitable or unsuitable for the request?
00:02:40.199 --> 00:02:49.560
Sometimes the population the sponsor is chosen is a disease subgroup that is not scientifically justified, so it doesn't qualify per the regulation.
00:02:50.069 --> 00:03:01.360
A broad example of this would be trying to request O D D for the pediatric population of a disease when your drug has the potential to safely and effectively treat patients of all ages.
00:03:02.400 --> 00:03:02.400
Okay.
00:03:02.401 --> 00:03:06.879
Can you elaborate a little more on what scientifically justified subgroups would be?
00:03:07.560 --> 00:03:08.050
Sure.
00:03:08.199 --> 00:03:15.449
Some diseases have subgroups which may exhibit different biological mechanisms, manifestations, disease severity, et cetera.
00:03:15.830 --> 00:03:25.129
For example, in oncology, these subgroups commonly include patients with a specific genetic aberration, which may not be present in the total disease population.
00:03:25.400 --> 00:03:36.930
What makes these groups scientifically justified in the eyes of the FDA is whether the subgroup is based on disease mechanisms which have a relationship to the drug or therapy which is intended to treat it.
00:03:36.949 --> 00:03:44.370
Essentially, the point is to prove that your drug will only work in these smaller groups and will likely not be effective for the broad indication.
00:03:44.969 --> 00:03:45.530
Right.
00:03:45.531 --> 00:03:58.849
So in situations where a sponsor has identified a subgroup of a specific indication, they need to carefully consider whether they have a scientifically justified subgroup or if they might really be guilty of what we refer to as salami slicing.
00:03:58.960 --> 00:04:11.050
Salami slicing is when we have a disease and we divide it into these artificial subgroups with the hope that each subgroup might be considered a rare disease, but really there's not scientific justification for that subgroup.
00:04:11.360 --> 00:04:13.370
Okay, thank you both for those explanations.
00:04:13.400 --> 00:04:22.170
I think it would be really helpful if we could get into some examples in order for folks to understand how a sponsor would scientifically justify an orphan subset.
00:04:22.579 --> 00:04:40.290
So I'll start, Let's assume that I'm the sponsor of a product intended to treat burn scars, which as a broad indication does not fall under the 200,000 prevalence requirement, but it looks like the prevalence for restrictive burn scars or scars that inhibit the range of motion around a joint is less than 200,000.
00:04:40.420 --> 00:04:47.569
So it seems like that could be a good target population for an O D D application and then we could later pursue the broader indication.
00:04:47.610 --> 00:04:48.569
Would that work?
00:04:48.860 --> 00:05:04.730
So Mara, that sounds like it might be an example of salami slicing unless you can provide an explanation for why the mechanism of your product is specific to restrictive burn scars as a subgroup rather than other types of burn scars or potentially all types of burn scars.
00:05:05.160 --> 00:05:05.649
Okay.
00:05:05.651 --> 00:05:14.329
So I would need to demonstrate as the sponsor that the mechanism of action of my drug is somehow specific to the restrictive or joint mobility scars as opposed to all scars.
00:05:14.480 --> 00:05:15.290
Yeah, Correct.
00:05:15.629 --> 00:05:16.170
Got it.
00:05:16.170 --> 00:05:16.610
Thank you.
00:05:16.829 --> 00:05:22.370
Can either of you share an example of a scientifically justified subgroup that would be appropriate for O D D?
00:05:23.120 --> 00:05:23.610
Sure.
00:05:23.660 --> 00:05:32.088
An example that Ellen actually alluded to earlier, and one that's becoming more common would be developing an oncology product to target a specific genetic variant.
00:05:32.338 --> 00:05:35.370
So let's take non-small cell lung cancer on its own.
00:05:35.370 --> 00:05:39.329
This type of cancer doesn't meet prevalence requirements for orphan drug designation.
00:05:39.699 --> 00:05:43.329
It actually accounts for like 80% of lung cancer diagnoses.
00:05:43.620 --> 00:05:49.810
However, there is a small percentage of non-small cell lung cancer patients who have an ALK mutation.
00:05:50.060 --> 00:05:54.730
So an ALK mutation causes cells in the lungs to grow up normally and behave like cancer cells.
00:05:55.060 --> 00:06:05.720
So this subgroup would meet prevalence requirements for orphan drug designation, but importantly in this example, my product's mechanism of action must be based on the presence of that ALK mutation.
00:06:06.170 --> 00:06:11.278
In that case, then my product wouldn't be effective in the larger non-small cell lung cancer indication.
00:06:11.449 --> 00:06:17.319
So this would be a good scientific justification for that ALK positive non-small cell lung cancer subgroup.
00:06:17.870 --> 00:06:19.519
Okay, thank you for that example.
00:06:19.540 --> 00:06:25.800
Can you expand a little on the type of data that would be needed to demonstrate that the drug is specific to that ALK mutation?
00:06:25.879 --> 00:06:27.600
Would that data need to be clinical?
00:06:28.189 --> 00:06:29.600
Yeah, that's a really good question.
00:06:29.850 --> 00:06:30.879
It could be clinical.
00:06:31.088 --> 00:06:38.160
It also could be data that a sponsor might generate earlier in product development, such as in vitro or in vivo non-clinical studies.
00:06:38.569 --> 00:06:49.720
As long as that data demonstrates that your product's mechanism of action is dependent on the presence of, for this example, that ALK mutation, then that uh, data would be supportive for your application.
00:06:50.480 --> 00:06:50.680
All right.
00:06:50.680 --> 00:06:51.360
Thanks a lot.
00:06:51.360 --> 00:06:51.759
Alexis.
00:06:51.949 --> 00:07:02.439
Have either of you seen examples of a product that received orphan designation where the applicability of the subgroup was not quite as straightforward as the non-small cell lung cancer example?
00:07:03.069 --> 00:07:03.560
Sure.
00:07:03.560 --> 00:07:11.240
One example I've seen, Mara, is a treatment to prevent recurrence of melanoma after resection, which was able to qualify for orphan drug.
00:07:11.259 --> 00:07:16.600
The treatment was designed to activate immune cells against the resurgence of cancerous melanoma cells.
00:07:16.839 --> 00:07:22.160
Therefore, it only really demonstrated efficacy against disease recurrence after surgical cure.
00:07:22.759 --> 00:07:29.879
Although melanoma overall does not qualify for orphan and it is actually one of the most commonly diagnosed cancers in the United States.
00:07:30.029 --> 00:07:42.800
A sponsor could justify exclusion of the early stage and pre resection patients from the target population using that understanding of the mechanism of the drug and likely lack of efficacy for other melanoma patients.
00:07:42.819 --> 00:07:48.000
The smaller subgroup was then justifies and then they had a successful O D D application.
00:07:48.430 --> 00:07:49.199
Okay, great.
00:07:49.389 --> 00:07:53.600
I really appreciate both of you attending today and giving us these examples.
00:07:53.740 --> 00:08:01.759
One, the Bern scar, one of a clearly artificial subgroup that wouldn't work for O D D and then to scientifically justified subgroup examples.
00:08:01.761 --> 00:08:04.000
I think that's really helpful for folks to understand.
00:08:04.009 --> 00:08:06.040
So thank you for providing that information.
00:08:06.350 --> 00:08:06.839
Sure.
00:08:06.841 --> 00:08:08.519
It was our pleasure to be here today.
00:08:08.750 --> 00:08:09.560
Yeah, definitely.
00:08:09.560 --> 00:08:10.319
Thank you, Mara.
00:08:10.449 --> 00:08:11.319
So we'll
00:08:11.319 --> 00:08:23.439
Leave our listeners with the recommendation that you leave the salami slicing for your charcuterie boards and make sure that you've carefully considered a scientifically supported rationale for your disease subgrouping for your orphaned drug designation request.
00:08:23.639 --> 00:08:24.199
Great.
00:08:24.201 --> 00:08:26.959
Thanks so much Alexis and Ellen for the discussion.
00:08:26.961 --> 00:08:30.360
I really appreciate you being here today to get your take on these topics.
00:08:30.930 --> 00:08:41.519
So just to wrap, Verta has a wealth of experience in all facets of clinical regulations and can help you develop a detailed strategic plan tailored to your product that will reduce your regulatory risk.
00:08:41.750 --> 00:08:49.440
I encourage you to listen to future episodes of our regulatory podcast series and to reach out through the links available on the various stat website.
00:08:49.620 --> 00:08:53.879
You can also subscribe to Art podcasts on your favorite podcast player.
00:08:54.450 --> 00:08:57.120
So thank you for listening, and until next time,
00:08:57.960 --> 00:08:59.360
Don't miss an episode.
00:09:00.000 --> 00:09:03.759
Subscribe to Art Podcasts on your favorite podcast player today.
00:00:01.229 --> 00:00:19.960
Bringing a novel therapeutic to market is an art Hear VAs stat thought leaders as they draw on their specialized expertise to offer insight on timely, relevant topics that impact clinical development, the regulatory landscape, and patient access to these novel therapies.
00:00:20.969 --> 00:00:28.879
Hi everyone, and welcome to Art Podcasts, Advancing Revolutionary Therapies, a podcast series presented by the Centers of Excellence at Vata.
00:00:29.250 --> 00:00:30.559
My name is Mara Hollinger.
00:00:30.560 --> 00:00:49.158
I'm the Senior Vice President of regulatory affairs here at Vata, and I'm delighted to kick off season three, a dedicated series of regulatory podcasts on topics that cover everything from smart regulatory strategies to maintaining continued regulatory compliance to the influence of health authorities on clinical trials and more.
00:00:49.719 --> 00:01:04.319
Today I'm joined by Alexis Northcutt, regulatory strategist and Ellen Truitt, associate regulatory strategist, both also with Baratt to discuss today's topics on orphan drug designation and specifically orphan subsets.
00:01:04.650 --> 00:01:06.560
So welcome Alexis and Allen.
00:01:06.561 --> 00:01:07.959
Thank you for joining today.
00:01:08.319 --> 00:01:09.319
Thank you, Mara.
00:01:09.319 --> 00:01:10.439
Happy to be here today.
00:01:10.590 --> 00:01:11.719
Yeah, thanks Mara.
00:01:11.721 --> 00:01:12.239
Me as well.
00:01:12.909 --> 00:01:19.000
Okay, I'm going to hand it right over to you, Alexis, to just explain in general what the Orphan Drug Designation Program is.
00:01:19.840 --> 00:01:20.329
Sure.
00:01:20.459 --> 00:01:32.489
So FDA's Orphan Drug Designation Program, which you will hear us referring to as O D D, is meant to provide incentives and support to encourage the development of treatment for rare diseases.
00:01:32.780 --> 00:01:47.930
So I don't think there's any argument that there have been incredible medical and scientific advances throughout the 20th and into the 21st centuries, but at some point in the seventies and eighties we began to realize that we were neglecting this smaller population of patients whose diseases just weren't that common.
00:01:48.500 --> 00:01:58.290
So this program gives FDA the authority to grant orphan drug status to a drug or a biologic that prevents diagnosis or treats an orphan or a rare disease.
00:01:58.620 --> 00:02:09.490
So some of these incentives that are included with this orphan drug designation are exemption of from user fees, potential for seven years of marketing exclusivity and tax credits for some clinical trials.
00:02:10.219 --> 00:02:11.319
And this is Ellen.
00:02:11.590 --> 00:02:19.479
I also wanted to add, you know, in order to be eligible for this designation, the disease must afflict less than 200,000 people in the us.
00:02:19.740 --> 00:02:32.680
One of the most common questions we get from sponsors seeking O D D is whether their population is appropriate, and in some cases, whether a chosen disease subgroup could be suitable for a successful O D D request.
00:02:33.560 --> 00:02:39.560
Ellen, could you expand on what would make a subgroup of a disease suitable or unsuitable for the request?
00:02:40.199 --> 00:02:49.560
Sometimes the population the sponsor is chosen is a disease subgroup that is not scientifically justified, so it doesn't qualify per the regulation.
00:02:50.069 --> 00:03:01.360
A broad example of this would be trying to request O D D for the pediatric population of a disease when your drug has the potential to safely and effectively treat patients of all ages.
00:03:02.400 --> 00:03:02.400
Okay.
00:03:02.401 --> 00:03:06.879
Can you elaborate a little more on what scientifically justified subgroups would be?
00:03:07.560 --> 00:03:08.050
Sure.
00:03:08.199 --> 00:03:15.449
Some diseases have subgroups which may exhibit different biological mechanisms, manifestations, disease severity, et cetera.
00:03:15.830 --> 00:03:25.129
For example, in oncology, these subgroups commonly include patients with a specific genetic aberration, which may not be present in the total disease population.
00:03:25.400 --> 00:03:36.930
What makes these groups scientifically justified in the eyes of the FDA is whether the subgroup is based on disease mechanisms which have a relationship to the drug or therapy which is intended to treat it.
00:03:36.949 --> 00:03:44.370
Essentially, the point is to prove that your drug will only work in these smaller groups and will likely not be effective for the broad indication.
00:03:44.969 --> 00:03:45.530
Right.
00:03:45.531 --> 00:03:58.849
So in situations where a sponsor has identified a subgroup of a specific indication, they need to carefully consider whether they have a scientifically justified subgroup or if they might really be guilty of what we refer to as salami slicing.
00:03:58.960 --> 00:04:11.050
Salami slicing is when we have a disease and we divide it into these artificial subgroups with the hope that each subgroup might be considered a rare disease, but really there's not scientific justification for that subgroup.
00:04:11.360 --> 00:04:13.370
Okay, thank you both for those explanations.
00:04:13.400 --> 00:04:22.170
I think it would be really helpful if we could get into some examples in order for folks to understand how a sponsor would scientifically justify an orphan subset.
00:04:22.579 --> 00:04:40.290
So I'll start, Let's assume that I'm the sponsor of a product intended to treat burn scars, which as a broad indication does not fall under the 200,000 prevalence requirement, but it looks like the prevalence for restrictive burn scars or scars that inhibit the range of motion around a joint is less than 200,000.
00:04:40.420 --> 00:04:47.569
So it seems like that could be a good target population for an O D D application and then we could later pursue the broader indication.
00:04:47.610 --> 00:04:48.569
Would that work?
00:04:48.860 --> 00:05:04.730
So Mara, that sounds like it might be an example of salami slicing unless you can provide an explanation for why the mechanism of your product is specific to restrictive burn scars as a subgroup rather than other types of burn scars or potentially all types of burn scars.
00:05:05.160 --> 00:05:05.649
Okay.
00:05:05.651 --> 00:05:14.329
So I would need to demonstrate as the sponsor that the mechanism of action of my drug is somehow specific to the restrictive or joint mobility scars as opposed to all scars.
00:05:14.480 --> 00:05:15.290
Yeah, Correct.
00:05:15.629 --> 00:05:16.170
Got it.
00:05:16.170 --> 00:05:16.610
Thank you.
00:05:16.829 --> 00:05:22.370
Can either of you share an example of a scientifically justified subgroup that would be appropriate for O D D?
00:05:23.120 --> 00:05:23.610
Sure.
00:05:23.660 --> 00:05:32.088
An example that Ellen actually alluded to earlier, and one that's becoming more common would be developing an oncology product to target a specific genetic variant.
00:05:32.338 --> 00:05:35.370
So let's take non-small cell lung cancer on its own.
00:05:35.370 --> 00:05:39.329
This type of cancer doesn't meet prevalence requirements for orphan drug designation.
00:05:39.699 --> 00:05:43.329
It actually accounts for like 80% of lung cancer diagnoses.
00:05:43.620 --> 00:05:49.810
However, there is a small percentage of non-small cell lung cancer patients who have an ALK mutation.
00:05:50.060 --> 00:05:54.730
So an ALK mutation causes cells in the lungs to grow up normally and behave like cancer cells.
00:05:55.060 --> 00:06:05.720
So this subgroup would meet prevalence requirements for orphan drug designation, but importantly in this example, my product's mechanism of action must be based on the presence of that ALK mutation.
00:06:06.170 --> 00:06:11.278
In that case, then my product wouldn't be effective in the larger non-small cell lung cancer indication.
00:06:11.449 --> 00:06:17.319
So this would be a good scientific justification for that ALK positive non-small cell lung cancer subgroup.
00:06:17.870 --> 00:06:19.519
Okay, thank you for that example.
00:06:19.540 --> 00:06:25.800
Can you expand a little on the type of data that would be needed to demonstrate that the drug is specific to that ALK mutation?
00:06:25.879 --> 00:06:27.600
Would that data need to be clinical?
00:06:28.189 --> 00:06:29.600
Yeah, that's a really good question.
00:06:29.850 --> 00:06:30.879
It could be clinical.
00:06:31.088 --> 00:06:38.160
It also could be data that a sponsor might generate earlier in product development, such as in vitro or in vivo non-clinical studies.
00:06:38.569 --> 00:06:49.720
As long as that data demonstrates that your product's mechanism of action is dependent on the presence of, for this example, that ALK mutation, then that uh, data would be supportive for your application.
00:06:50.480 --> 00:06:50.680
All right.
00:06:50.680 --> 00:06:51.360
Thanks a lot.
00:06:51.360 --> 00:06:51.759
Alexis.
00:06:51.949 --> 00:07:02.439
Have either of you seen examples of a product that received orphan designation where the applicability of the subgroup was not quite as straightforward as the non-small cell lung cancer example?
00:07:03.069 --> 00:07:03.560
Sure.
00:07:03.560 --> 00:07:11.240
One example I've seen, Mara, is a treatment to prevent recurrence of melanoma after resection, which was able to qualify for orphan drug.
00:07:11.259 --> 00:07:16.600
The treatment was designed to activate immune cells against the resurgence of cancerous melanoma cells.
00:07:16.839 --> 00:07:22.160
Therefore, it only really demonstrated efficacy against disease recurrence after surgical cure.
00:07:22.759 --> 00:07:29.879
Although melanoma overall does not qualify for orphan and it is actually one of the most commonly diagnosed cancers in the United States.
00:07:30.029 --> 00:07:42.800
A sponsor could justify exclusion of the early stage and pre resection patients from the target population using that understanding of the mechanism of the drug and likely lack of efficacy for other melanoma patients.
00:07:42.819 --> 00:07:48.000
The smaller subgroup was then justifies and then they had a successful O D D application.
00:07:48.430 --> 00:07:49.199
Okay, great.
00:07:49.389 --> 00:07:53.600
I really appreciate both of you attending today and giving us these examples.
00:07:53.740 --> 00:08:01.759
One, the Bern scar, one of a clearly artificial subgroup that wouldn't work for O D D and then to scientifically justified subgroup examples.
00:08:01.761 --> 00:08:04.000
I think that's really helpful for folks to understand.
00:08:04.009 --> 00:08:06.040
So thank you for providing that information.
00:08:06.350 --> 00:08:06.839
Sure.
00:08:06.841 --> 00:08:08.519
It was our pleasure to be here today.
00:08:08.750 --> 00:08:09.560
Yeah, definitely.
00:08:09.560 --> 00:08:10.319
Thank you, Mara.
00:08:10.449 --> 00:08:11.319
So we'll
00:08:11.319 --> 00:08:23.439
Leave our listeners with the recommendation that you leave the salami slicing for your charcuterie boards and make sure that you've carefully considered a scientifically supported rationale for your disease subgrouping for your orphaned drug designation request.
00:08:23.639 --> 00:08:24.199
Great.
00:08:24.201 --> 00:08:26.959
Thanks so much Alexis and Ellen for the discussion.
00:08:26.961 --> 00:08:30.360
I really appreciate you being here today to get your take on these topics.
00:08:30.930 --> 00:08:41.519
So just to wrap, Verta has a wealth of experience in all facets of clinical regulations and can help you develop a detailed strategic plan tailored to your product that will reduce your regulatory risk.
00:08:41.750 --> 00:08:49.440
I encourage you to listen to future episodes of our regulatory podcast series and to reach out through the links available on the various stat website.
00:08:49.620 --> 00:08:53.879
You can also subscribe to Art podcasts on your favorite podcast player.
00:08:54.450 --> 00:08:57.120
So thank you for listening, and until next time,
00:08:57.960 --> 00:08:59.360
Don't miss an episode.
00:09:00.000 --> 00:09:03.759
Subscribe to Art Podcasts on your favorite podcast player today.
