Gene Therapy Pipeline and Portfolio Analysis

Report
109 Pages
April 2019
Region: Global
Citeline
ID: 4846149

Overview
Gene therapy has undergone transformative enhancements over the last 20 years, with improvements to technologies and advances in the pipeline that aim to invigorate the field in its second generation. A dozen products have made it to various markets worldwide, including several within the last few years, and more are expected to gain approval soon. The pipeline is dominated by oncology ex vivo targets, but there are many approaches being pursued by key players outside of this core area.

Gene therapy has overcome setbacks since its inception in the early 1970s

The death of a patient with partial ornithine transcarbamylase (OTC) deficiency in 1999, as well as reports of leukemia following delivery of gene therapy in the early 2000s, deterred development for some years; however, the current generation has benefited from improvements to technology and drug delivery.

Gene therapy developers have employed both viral and non-viral methods to deliver genes

There are several advantages to using either viral or non-viral vectors, with the former offering efficient gene transfer, and the latter leading to lower costs and greater biosafety. But both also come with drawbacks that are prompting evaluation of other delivery methods.

The EMA and FDA have both introduced regulations that foster regenerative medicine development

The EMA introduced a regulation in 2007 that created a regulatory framework for advanced therapy medicinal products (ATMPs), and the FDA established the regenerative medicine advanced therapy (RMAT) pathway in 2016 through the passage of the 21st Century Cures Act. Gene therapies are part of the scopes of both, and sponsors may take advantage of frequent interactions with regulators plus other benefits.

Hundreds of companies are involved in gene therapy development

There are approximately 427 unique companies – acting as originators or licensees – with development-stage candidates. These include very small players working on only one or two therapies, all the way up to more active companies with larger pipelines totaling around 20 programs.

Globally, there are 12 approved or launched gene therapies in the market

At the end of Q1 2019, there are 12 gene therapies approved or launched worldwide, including a nearly equal split of in vivo (seven) and ex vivo (five) therapies. All but two of the products are delivered by viral vectors, and most of the launches have been in Europe, followed by Asia.

Just over half of the pipeline is comprised of in vivo therapies

A slight majority (52%) of the pipeline is delivered in vivo. The rest of the candidates are cell and gene therapies, and within this group 57% are autologous as opposed to allogeneic. The approach taken – in vivo (gene therapy) or ex vivo (cell and gene therapy) – varies depending on many factors, including the site of the disease and how accessible those targets are.

Solid tumors are the major focus of oncology gene therapy development

The majority of oncology gene therapies (57%) are looking to address solid tumors, but hematological cancers also have a strong proportion (43%) of development in the area.

OVERVIEW

INTRODUCTION TO GENE THERAPY

The author's insights and recommendations
Gene therapy is the most active modality in regenerative medicine
Historically, gene therapy has been riddled with setbacks
Gene therapy involves in vivo and ex vivo approaches
Bibliography

INNOVATIONS IN GENE DELIVERY TECHNOLOGIES

The author's insights and recommendations
Gene therapy is enabled by viral and non-viral methods
Bibliography

REGULATORY ISSUES

The author's insights and recommendations
Regulatory pathways are providing incentives for gene therapy development
Bibliography

KEY COMPANIES IN GENE THERAPY

The author's insights and recommendations
Hundreds of companies are involved in gene therapy development
Regenxbio is building its internal pipeline and out-licensing its NAV platform
Now owned by Celgene, Juno is pushing ahead with a third-to-market CAR-T
Kite Pharma's cell therapy pipeline will become the foundation of Gilead's oncology offering
CAR-T therapy and directly administered gene therapy are both focuses for Novartis
Sarepta targets gene therapies for muscular dystrophies
Through collaborations and in-house development, bluebird bio is moving forward with ex vivo gene therapies in multiple diseases
Bibliography

TRENDS IN APPROVED GENE THERAPIES

The author's insig
A dozen gene therapies are approved worldwide
Key gene therapy approvals
Bibliography

GENE THERAPY PIPELINE TRENDS

The author's insights and recommendations
After plateauing, the gene therapy pipeline is picking up speed
The US leads ongoing clinical trial activity in gene therapies
Completed gene therapy trials have high success rates
Most terminated gene therapy trials are those that were planned but never initiated
Both gene therapy and cell and gene therapy approaches are on fairly equal ground
Across phases, in vivo and ex vivo therapies are split fairly equally
Viral vectors are used more than non-viral vectors for delivery
Most gene therapies in development aim to attack rare diseases and cancer
Outside of oncology, different diseases emerge in the lead among in vivo and ex vivo therapies
Bibliography

ONCOLOGY GENE THERAPY TRENDS

The author's insights and recommendations
The majority of gene therapies in the pipeline are for solid tumors
CAR therapies are dominant in ex vivo development

APPENDIX

Scope
Methodology

LIST OF FIGURES

Figure 1: Gene therapy defined: EMA and FDA definitions
Figure 2: Gene therapy delivery approaches, in vivo versus ex vivo
Figure 3: Viral and non-viral vectors – advantages and disadvantages
Figure 4: Key viral vector types – advantages and disadvantages
Figure 5: Product class inclusions in EU and US specialized regenerative medicine regulatory pathways
Figure 6: Most active gene therapy companies, by pipeline size
Figure 7: Most approved or launched gene therapies are available in Europe
Figure 8: Gene therapy pipeline volume, preclinical through pre-registration phase, 1995–2018
Figure 9: Gene therapy pipeline volume by phase, 1995–2018
Figure 10: Most gene therapy clinical trial activity is in the US
Figure 11: Completed gene therapy trials are largely successful; trials by outcomes
Figure 12: Top reasons why gene therapy trials are terminated
Figure 13: Gene therapy versus cell and gene therapy: breakdown of pipeline
Figure 14: Gene therapy pipeline, by in vivo or ex vivo approach and phase
Figure 15: Ex vivo gene therapy pipeline, by cell type and phase
Figure 16: Viral vector delivery is most prominent in gene therapy
Figure 17: In viral vector gene delivery, AAVs are most often used
Figure 18: Viral vector gene therapy pipeline, by vector and phase
Figure 19: In vivo gene therapies, viral versus non-viral delivery
Figure 20: In vivo gene therapies, by vector type
Figure 21: Ex vivo gene therapies, viral versus non-viral delivery
Figure 22: Ex vivo gene therapies, by vector type
Figure 23: Rare disease and oncology dominate gene therapy drug development
Figure 24: Gene therapy pipeline, by therapy area and phase
Figure 25: Cancer and non-oncologic rare disease diverge in ex vivo versus in vivo delivery
Figure 26: Viral vectors are largely used in both cancer and rare non-oncologic gene therapies
Figure 27: Other therapy areas are mostly being addressed by in vivo therapy
Figure 28: Viral vectors are also most prominent in other therapy areas
Figure 29: In vivo gene therapies, by therapy area and viral vector
Figure 30: Ex vivo gene therapies, by therapy area and viral vector
Figure 31: Lead molecular targets among in vivo therapies
Figure 32: Lead molecular targets among ex vivo therapies
Figure 33: Lead indications among non-oncology in vivo therapies
Figure 34: Lead indications among non-oncology ex vivo therapies
Figure 35: Oncology gene therapies are mainly addressing solid tumors
Figure 36: Developers focus on ex vivo therapy in cancer
Figure 37: Tumor type distribution between in vivo and ex vivo therapies in oncology
Figure 38: Top 20 oncology indications in gene therapy development, by approach
Figure 39: CAR therapies dominate: oncology ex vivo gene therapies, by approach
Figure 40: Ex vivo oncology approaches, by phase
Figure 41: Autologous versus allogeneic delivery in oncology ex vivo CAR therapies

LIST OF TABLES

Table 1: Summary of FDA guidance on cell and gene therapy
Table 2: REGENXBIO gene therapy pipeline
Table 3: Juno Therapeutics/Celgene gene therapy pipeline
Table 4: Kite Pharma/Gilead gene therapy pipeline
Table 5: Novartis gene therapy pipeline
Table 6: Sarepta gene therapy pipeline
Table 7: Bluebird bio gene therapy pipeline
Table 8: Approved gene therapies worldwide, as of Q1 2019

Table of Contents

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