Insights into the Rare Disease Drug Approval Landscape: Trends and Current Development

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1 Insights into the Rare Disease Drug Approval Landscape: Trends and Current Development Mike Lanthier Operations Research Analyst FDA Office of the Commissioner NORD Rare Diseases & Orphan Products Breakthrough Summit October 18, 2016

2 Measuring Trends in Drug Innovation: 2

3 Definition of Innovation Categories first in class a drug that demonstrates a new way to affect a physiologic change in a disease/condition advance in class an addition to an existing class of drugs which is granted a FDA priority review. Priority review is granted to drugs with the potential to deliver a significant improvement in safety or effectiveness over existing therapy for serious or life-threatening illnesses addition to class - an addition to an existing class of drugs that receives a standard FDA review and does not appear to be provide a significant advantage relative to existing therapies. 3

4 New Molecular Entities (NMEs) Approved by Innovation Category adapted from: Kathleen L. Miller, and Michael Lanthier Health Aff 2016;35:

5 New Molecular Entities (NMEs) Approved by Innovation Category 5

6 What do we know about the rare disease pipeline? past performance is no guarantee of future results What might we expect the orphan drug approval trend look like over the next few years? Perhaps taking a look at sponsor engagement with FDA regulatory programs aimed at expediting drug development can provide a glimpse into where developers are currently focusing their efforts. 6

7 Number of Orphan Designations Granted * Source: Office of Orphan Products Development database. September,

8 Fast Track and Breakthrough Designation Programs Fast Track (designation) for drugs intended to treat a serious condition where data demonstrate the potential to address an unmet medical need. Closer interaction with FDA on the drug development plan Portions of the Marketing Application can be submitted in advance of the entire application, on a rolling review basis Breakthrough (designation) - for drugs intended to treat a serious condition where preliminary clinical evidence indicates that the drug may demonstrate a substantial improvement over available therapies All program features of Fast Track designation, including intensive guidance from FDA, to help sponsors better tailor their drug development program Organizational commitment from FDA s senior managers and experienced review staff to collaborate in advancing the review of these potentially high-impact drugs 8 For further details, see Guidance for Industry Expedited Programs for Serious Conditions - Drugs and Biologics : 8

9 Utilization of Fast Track and Breakthrough Designations by Disease Prevalence CDER Novel Drugs Approved January 2013 June

10 How might sponsor engagement with these designation programs inform us about the rare disease development pipeline? Roughly two-thirds of novel orphan drugs approved in recent years received either a fast track or breakthrough designation. These designations are customarily occur around the end-of-phase 2 or beyond, and therefore generally reflect drugs advancing into later phases of clinical development. In order to receive FT or BT designation the sponsor must provide FDA with evidence demonstrating that the drug has potential to address an unmet medical need. Therefore, an analysis of products receiving these designations may provide a insights into potential new therapies for rare conditions that are currently under late stage development. 10

11 Analysis of CDER Fast Track and Breakthrough Designations Granted between Fast Track Designations granted letters issued between Jan 2006 and Dec Breakthrough Designations granted between Nov 2012 and December discrete designated drug/indication combinations (some products received both FT and BT designations) across 643 discrete drug products (some drug products have more than one indication for which FT or BT was granted) For all 671 products we identified whether the drug appears to be novel (a new molecular entity or novel biologic product), whether or not the drug s indication for which BT or FT was granted was indicated for a rare disorder, and whether or not the drug was for a cancer or non-cancer indication. For a subset of 260 products which were determined to be both novel and rare, we used FDA internal documentation, public information on product development, ClinicalTrials.gov and PharmaProjects databases to approximate the phase of development (or discontinuation) for each product + indication 11

12 CDER Novel Rare Disease Products Receiving Fast Track Designation by Therapeutic Area *Cancer therapeutic category includes both solid tumor and hematological malignancies, as well as drugs used in cancer supportive care. The Hematology category are non-oncology conditions, primarily inherited blood disorders. 12

13 CDER Novel Rare Disease Products Receiving Breakthrough Designation by Therapeutic Area *Cancer therapeutic category includes both solid tumor and hematological malignancies, as well as drugs used in cancer supportive care. The Hematology category includes non-oncology conditions, primarily inherited blood disorders. 13

14 Novel Rare Disease Products Receiving Fast Track and/or Breakthrough Designation Designated by Phase of Development 14

15 Novel Rare Disease Fast Track Designation Outcomes Designations Occurring January 2006 December 2010 Cancer (n = 34) Non-Cancer (n = 53) 15

16 Limitations and Caveats: These data represent an incomplete picture of the rare disease development pipeline. Not all sponsors seek (nor are granted) fast track designation for their products There are likely some products that have been in fast track development prior to 2006 that remain in active development Although this analysis focuses on novel orphan products, there are also numerous orphan drug development programs investigating potentially valuable new uses for existing drugs It is possible that the increase in Fast Track designations simply indicates greater utilization of FDAs expedited development tools, rather than an increase in the pipeline of orphan products However, these increases correspond with observed increases in orphan designations Such a dramatic increase in FT designations in the non-cancer space, while at the same time oncology fast track rates remain essentially unchanged, seems to indicate something more is going on than just simply increased designations Regardless, increased engagement with FDA on rare disease development programs would certainly appear to be an encouraging sign Increases in designations do not guarantee future increases in marketing approvals. There will always be considerable amount of uncertainty surrounding development success rates for groundbreaking drugs in new therapeutic areas 16

17 Parting thoughts: Orphan drugs are on average highly innovative products, often representing new an improved ways to treat serious conditions and address unmet medical needs. Orphan drugs, many of which have been innovative first-in-class treatments, have been played a major role in the recent observed increase in novel drug approvals Fast track designations for rare disease drugs in development have surged over the past two years, with a remarkable increase in designations for non-cancer indications. More than half of all Breakthrough Therapy designations granted by FDA have been for treatment of rare diseases, generally split evenly between cancer and non-cancer indications. Although the majority of novel orphan drug approvals in recent years have occurred in the oncology space, a large proportion of FT/BT-designated products in late-stage development are for indications other than cancer. These data may indicate a growing willingness by developers to build off the recent success of rare oncology approvals and expand their development programs into other non-cancer rare conditions. Given our finding that more than 1/3 of fast track designated drugs resulted a marketing approval, coupled with a recent increase in such designations, there appear to be many opportunities in the pipeline for novel drugs to address unmet medical needs for patients facing rare diseases. 17

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