Clearly, CGTs have not taken the same development path as MAbs, and those paths are unlikely to converge unless one of the modalities shows differentiated benefits for productivity, purity, and applicability. However, manufacturing processes have improved dramatically since production of the worlds first CGT products, as has industry and regulatory understanding about the safety profiles and characterization requirements for such products. But the CGT industry has much further to go.
The State of the CGT Industry
A major question that lingers along the development path is whether gene therapies will continue addressing monogenic targets or expand to multigenic indications. Despite efforts to match the productivity of processes for other biopharmaceuticals, improvements to CGT-process productivity have been stepwise rather than transformative, and such changes generally have not met expectations. One result is that after 20 years, CGTs largely remain focused on treating small patient populations with specific medical needs. Small production volumes also have led to high prices, which have been justifiable for early entrants to the CGT space but will be unsustainable in the long term.
Until the past few years, suppliers of raw materials, cell-culture media, and bioprocess equipment largely have ignored the CGT space. The market had been perceived as too small and unproven to provide profitable opportunities. Luckily, commercial success has driven most suppliers to recognize the CGT industry as a viable market that needs special attention. Today, equipment is designed solely for cell therapy applications or viral vector manufacturing. Raw materials such as plasmids have increased both in quality and availability. Most suppliers have awakened to the potential of CGT commercial success, especially considering that clinical timelines for most such products are condensed compared with those for MAbs and other biologics.
The Story of Oxford Biomedica
My employer, Oxford Biomedica, also has been involved in gene therapy production for over 25 years. Oxford Biomedica has been a biotechnology company for much of its history, and weve built lentiviral (LV) manufacturing technology to support in-house production of our products. Like many other candidate therapies, our lead programs did not progress through clinical studies, and weve moved on to other indications. But our hard work in gene-therapy development, manufacturing, analytics, quality control (QC), and regulatory affairs has paid off nicely because other companies have recognized the depth of our expertise. Weve forged licensing partnerships so that our technology can be used by multiple companies rather than just one.
We capitalized on that business model in January 2022 when we worked with Homology Medicines to form a new entity called Oxford Biomedica Solutions to focus on adenoassociated virus (AAV) development and manufacturing. The hard work that was put into developing AAV manufacturing expertise now is readily available to partner organizations rather than held closely within one company. The decision to form Oxford Biomedica Solutions speaks to the importance of sharing lessons learned from taking products from early clinical phases through commercial manufacturing with partner companies that want to benefit from such experience.
Personal Reflections on CGT Development
From a business perspective, CGT companies have needed to navigate a series of ups and downs. Such a process isnt for the faint of heart.
Early in my career, only academic centers, a few biotechnology companies, and a large pharmaceutical company or two engaged with gene-therapy technologies. In 1999, the tragic death of Jesse Gelsinger, the first person to die during a clinical trial for gene therapy, dropped the industry to its knees. Most large pharmaceutical companies stopped funding gene therapy projects, but a small number of true believers persisted with the technology, developing safer and better vector systems and improving clinical trial design and support.
It was only 10 years ago that two fundamental technologies were found to be effective for gene therapy: AAV vectors were found to be effective in delivering therapeutic genes for certain monogenic rare diseases, and patients treated with CAR-T products showed spectacularly improved rates of complete responses to blood cancers. Companies and investors started to take notice. In 2019, when AveXis/Novartis began commercializing Zolgensma (onasemnogene abeparvovec-xioi) as a treatment for spinal muscular atrophy (SMA), I was among many scientists who felt that the drugs regulatory approval was just the validation that the CGT industry needed.
My work in CGT is personal. My 21-year-old daughter suffers from Rett syndrome (RTS, cerebroatrophic hyperammonemia), a rare, monogenic neurological disease. Sadly, a cure is not yet available but developers are still trying. The challenges that my family has encountered while seeking out RTS treatments mirror some of the obstacles that face the CGT industry. Manufacturing processes remain small and fragmented, although they have moved largely to mammalian cell cultures in suspension bioreactors, which will provide scalability advantages. AAV vectors work best when the serotype used matches to a target organ, but results have been inconsistent. Increasingly, the US Food and Drug Administration (FDA) insists on characterization of AAV products, even for early phase clinical trials. A number of clinical holds have occurred for AAV-based gene therapies. Thus, Oxford Biomedica believes, as do many drug companies, that AAV needs to be manufactured using a scalable process that can deliver high levels of full, infectious particles; that qualified analytics should be established at the earliest possible stage; and that impurities, including empty capsids, must be closely monitored and reduced.
Guarded Optimism for the CGT Industry
Ive worked for both drug developers and service providers within the CGT industry, so I am in the novel position of having been on both sides of the table. The macrodynamics of outsourcing have changed dramatically over the past five years. What had been a largely underserved marketplace now has become inundated with large multinational pharmaceutical companies, specialty providers, and academic centers. Companies that suffered through 1824 months of waiting in a manufacturers queue have decided to build their own capacity. And the few manufacturing specialists with CGT capabilities have found themselves becoming critically important as the talent pool has thinned out among the industrys many offerings. This current situation, when combined with our uncertain economic environment, is putting internal and external manufacturing capacity under renewed focus.
I am hopeful but realistic about the next 10 years of the CGT industry. The COVID-19 pandemic has shown us that under certain circumstances, new technologies such as mRNA can be developed and scaled rapidly. Cell therapies are likely to improve in quality and scale through automation of production processes. Improvements also might come from transitions from autologous to allogeneic processes or from novel applications such as in vivo delivery of CAR T cells. I hope that gene therapies will move to even more scalable processes, with well-considered regulatory guidelines particularly for AAV-based therapies established to help minimize patient and manufacturing risks. And just maybe, we can treat not only rare diseases such as what my daughter has, but also larger indications. Doing so will support the future of the industry.
David Backer is chief commercial officer at Oxford Biomedica in Oxford, UK; d.backer@oxb.com; https://www.oxb.com.
See the article here:
Taking a Distinctive Path Reflections on the History of Gene Therapy Development - BioProcess Insider
- Stem Cell Therapy for Kidney Failure [Last Updated On: April 1st, 2011] [Originally Added On: April 1st, 2011]
- Dogged by pain -- stem cell therapy for dogs [Last Updated On: June 24th, 2013] [Originally Added On: April 3rd, 2011]
- Dogs now getting stem cell therapy [Last Updated On: April 8th, 2011] [Originally Added On: April 8th, 2011]
- Stem Cells for Spinal Cord Injury: Community Outreach San Diego 2011 - Trish Stressman [Last Updated On: April 11th, 2011] [Originally Added On: April 11th, 2011]
- Stem Cell Treatment Doing Wonders For Autistic Boy [Last Updated On: April 14th, 2011] [Originally Added On: April 14th, 2011]
- Is Stem Cell Therapy right for your pet [Last Updated On: April 14th, 2011] [Originally Added On: April 14th, 2011]
- Regenerative Medicines [Last Updated On: May 19th, 2011] [Originally Added On: May 19th, 2011]
- Stem Cell Therapy for Multiple Sclerosis [Last Updated On: June 24th, 2013] [Originally Added On: May 20th, 2011]
- Adult Stem Cell Therapy for Multiple Sclerosis [Last Updated On: May 23rd, 2011] [Originally Added On: May 23rd, 2011]
- Heart Failure Patient After Adult Stem Cell Therapy [Last Updated On: June 24th, 2013] [Originally Added On: May 30th, 2011]
- Stem Cell Therapy For Alzheimer's/Dementia [Last Updated On: June 24th, 2013] [Originally Added On: June 2nd, 2011]
- Stem Cell Therapy For Alzheimer's/Dementia [Last Updated On: June 7th, 2011] [Originally Added On: June 7th, 2011]
- Stem Cell Therapy Injections [Last Updated On: June 24th, 2013] [Originally Added On: June 8th, 2011]
- Clinical Advances in Adult Stem Cell Therapy: Dr. Jorge Paz [Last Updated On: June 24th, 2013] [Originally Added On: June 11th, 2011]
- Stem Cell Therapy MS: Sam Harrell and The Superbowl [Last Updated On: June 12th, 2011] [Originally Added On: June 12th, 2011]
- Stem Cell Therapy MS: Sam Harrell and The Superbowl [Last Updated On: June 24th, 2013] [Originally Added On: June 14th, 2011]
- Lou Gehrig's Disease (ALS): UCSD Team's Stem Cell Therapy Rationale [Last Updated On: June 14th, 2011] [Originally Added On: June 14th, 2011]
- Stem Cell Injection Treatment - Stem Cell Therapy [Last Updated On: June 18th, 2011] [Originally Added On: June 18th, 2011]
- edivet America Dog Arthritis Stem Cell Therapy Stem Cell Therapy for Equine 1 [Last Updated On: June 24th, 2013] [Originally Added On: June 23rd, 2011]
- Lou Gehrig's Disease (ALS): UCSD Team's Stem Cell Therapy Approach [Last Updated On: June 25th, 2011] [Originally Added On: June 25th, 2011]
- Adult Stem Cell Therapy Clinical Advances - Dr. Jorge Paz in San Diego, CA March 2011 [Last Updated On: July 3rd, 2011] [Originally Added On: July 3rd, 2011]
- Adult Stem Cell Therapy Clinical Advances - Dr. Jorge Paz in San Diego, CA March 2011 [Last Updated On: June 24th, 2013] [Originally Added On: July 15th, 2011]
- Duffy Gets Stem Cell Therapy [Last Updated On: June 24th, 2013] [Originally Added On: July 15th, 2011]
- WAVE3 News Adipose Stem Cell Therapy [Last Updated On: June 24th, 2013] [Originally Added On: July 16th, 2011]
- Lou Gehrig's Disease (ALS): UCSD Team's Stem Cell Therapy Approach [Last Updated On: June 24th, 2013] [Originally Added On: July 16th, 2011]
- Clinical Advances in Adult Stem Cell Therapy - Dr. Jorge Paz Rodriguez (Miami) [Last Updated On: June 24th, 2013] [Originally Added On: July 21st, 2011]
- Stem Cell Therapy for Cerebral Palsy - Holly Catalano [Last Updated On: June 24th, 2013] [Originally Added On: August 2nd, 2011]
- Bone Marrow Aspiration - Stem Cell Therapy [Last Updated On: August 5th, 2011] [Originally Added On: August 5th, 2011]
- Dr. Chein discusses Autologous Stem Cell Therapy - Palm Springs [Last Updated On: June 24th, 2013] [Originally Added On: August 12th, 2011]
- Stroke Victim Improved With Stem Cell Therapy. More at http://www.stemcellfusion.com [Last Updated On: June 24th, 2013] [Originally Added On: August 14th, 2011]
- Dr. Craig Saunders Adult Stem Cell Therapy [Last Updated On: August 15th, 2011] [Originally Added On: August 15th, 2011]
- Embryonic stem cell therapy in China (www.esctherapy.com) [Last Updated On: June 24th, 2013] [Originally Added On: August 16th, 2011]
- Ying Liu discusses IPS cell therapy for ALS [Last Updated On: June 24th, 2013] [Originally Added On: August 16th, 2011]
- Stem Cell Therapy: Healing Force of the future [Last Updated On: September 19th, 2011] [Originally Added On: September 19th, 2011]
- Benefits of STEM CELL THERAPY - Adipose Tissue [Last Updated On: September 22nd, 2011] [Originally Added On: September 22nd, 2011]
- Stem Cell Therapy Skin Repair and Anti-Wrinkle Cream [Last Updated On: June 24th, 2013] [Originally Added On: September 24th, 2011]
- Cardiac Stem Cell Therapy [Last Updated On: June 24th, 2013] [Originally Added On: September 24th, 2011]
- Holly Huber on Recovery: Stem Cell Therapy for Multiple Sclerosis Community Outreach Dallas, TX 2011 [Last Updated On: June 24th, 2013] [Originally Added On: September 24th, 2011]
- Stroke Victim Improved With Stem Cell Therapy. More at http://www.stemcellfusion.com [Last Updated On: September 25th, 2011] [Originally Added On: September 25th, 2011]
- A Touch of Love® - Stem Cell Therapy for Pets-Dr. Danny DeRose-Part 3 [Last Updated On: September 27th, 2011] [Originally Added On: September 27th, 2011]
- Adult Stem Cell Therapy for Multiple Sclerosis [Last Updated On: June 24th, 2013] [Originally Added On: September 28th, 2011]
- Multiple Sclerosis Stem Cell Therapy News Coverage [Last Updated On: June 24th, 2013] [Originally Added On: October 1st, 2011]
- The Spinal Cord Journey - Stem cell therapy stories from three spinal cord injury patients [Last Updated On: October 6th, 2011] [Originally Added On: October 6th, 2011]
- Peyton Manning Stem Cell Therapy: Some Doctors Cry Foul Over European Treatment - Video [Last Updated On: October 13th, 2011] [Originally Added On: October 13th, 2011]
- Stem-Cell-Therapy-in-China.wmv - Video [Last Updated On: October 13th, 2011] [Originally Added On: October 13th, 2011]
- Randolph veterinarian uses new stem cell therapy on ailing pets - Video [Last Updated On: June 24th, 2013] [Originally Added On: October 13th, 2011]
- Stem Cell Therapy for Rheumatoid Arthritis - Video [Last Updated On: June 24th, 2013] [Originally Added On: October 14th, 2011]
- Holly Huber on Recovery: Stem Cell Therapy for Multiple Sclerosis Community Outreach Dallas, TX 2011 - Video [Last Updated On: October 14th, 2011] [Originally Added On: October 14th, 2011]
- Affordable Stem Cell Therapy in Guatemala (2hrs from Miami) - Video [Last Updated On: June 24th, 2013] [Originally Added On: October 15th, 2011]
- Stem Cell Research: Macular Degeneration - Video [Last Updated On: October 18th, 2011] [Originally Added On: October 18th, 2011]
- Duffy Gets Stem Cell Therapy - Video [Last Updated On: October 18th, 2011] [Originally Added On: October 18th, 2011]
- VetCell's StemRegen - the original and best stem cell therapy for equine tendon injuries - Video [Last Updated On: October 20th, 2011] [Originally Added On: October 20th, 2011]
- Macular degeneration - Stem Cell therapy (English subtitles) - Video [Last Updated On: October 20th, 2011] [Originally Added On: October 20th, 2011]
- Stem Cell Therapy for Rheumatoid Arthritis - Community Outreach Dallas - Darnell Morris - Video [Last Updated On: June 24th, 2013] [Originally Added On: October 21st, 2011]
- Adult Stem Cell Therapy for Congestive Heart Failure [Last Updated On: June 24th, 2013] [Originally Added On: October 21st, 2011]
- Stem Cell Therapy for Critical Limb Ischemia: First Choice or Last Ditch? - Video [Last Updated On: October 22nd, 2011] [Originally Added On: October 22nd, 2011]
- WAVE3News Adipose Stem Cell Therapy - Video [Last Updated On: October 22nd, 2011] [Originally Added On: October 22nd, 2011]
- Stem Cell Therapy in Cardiac Disease - Video [Last Updated On: June 24th, 2013] [Originally Added On: October 24th, 2011]
- Stem Cell Treatment for Autism: Community Outreach Miami, Florida - May 2011 - Video [Last Updated On: June 24th, 2013] [Originally Added On: October 24th, 2011]
- Pre Post n 6 Months Post Stem Cell Therapy of Dystonic Cerebral Palsy - Video [Last Updated On: June 24th, 2013] [Originally Added On: October 24th, 2011]
- Stem Cell Treatment for Rheumatoid Arthritis - "I am basically pain free." - Video [Last Updated On: October 26th, 2011] [Originally Added On: October 26th, 2011]
- UMBILICAL CORD STEM CELL THERAPY - Video [Last Updated On: June 24th, 2013] [Originally Added On: October 26th, 2011]
- Stem Cell Therapy for Peripheral Artery Disease - Video [Last Updated On: June 24th, 2013] [Originally Added On: October 26th, 2011]
- Multiple Sclerosis Adult Stem Cell Therapy - Video [Last Updated On: June 24th, 2013] [Originally Added On: October 26th, 2011]
- Stem Cell Therapy for Multiple Sclerosis Stimulates IDO - Video [Last Updated On: June 24th, 2013] [Originally Added On: October 26th, 2011]
- HIV/AIDS: Spotlight on Stem Cell Research - John Zaia - Video [Last Updated On: October 26th, 2011] [Originally Added On: October 26th, 2011]
- Stem cell treatment by Adiva Health Care India after Spinal Cord Injury - Video [Last Updated On: October 27th, 2011] [Originally Added On: October 27th, 2011]
- Stem Cell Treatment for Spinal Cord Injury - Video [Last Updated On: October 28th, 2011] [Originally Added On: October 28th, 2011]
- Lou Gehrig's Disease: Stem Cell Therapy Pre-Clinical Studies - Video [Last Updated On: October 28th, 2011] [Originally Added On: October 28th, 2011]
- Stem Cell Treatment for Spinal Cord Injury - Video [Last Updated On: June 24th, 2013] [Originally Added On: October 28th, 2011]
- Holly Huber on Recovery: Stem Cell Therapy for Multiple Sclerosis Community Outreach San Diego CA - Video [Last Updated On: June 24th, 2013] [Originally Added On: October 28th, 2011]
- Stem Cell Treatment for Rheumatoid Arthritis - "I got my life back" - Video [Last Updated On: October 28th, 2011] [Originally Added On: October 28th, 2011]
- Adult Stem Cell Therapy Following Heart Attack and Stroke - Video [Last Updated On: October 28th, 2011] [Originally Added On: October 28th, 2011]
- Stem Cells - Treatment for Autism - Video [Last Updated On: November 2nd, 2011] [Originally Added On: November 2nd, 2011]
- Stem Cell Treatment Diabetes - Video [Last Updated On: November 7th, 2011] [Originally Added On: November 7th, 2011]
- Stem Cell Therapy: Psoriatic Arthritis Treatment - Video [Last Updated On: June 24th, 2013] [Originally Added On: November 8th, 2011]
- Stem Cell Therapy Cure Hair Loss. More at http://www.stemcellfusion.com - Video [Last Updated On: June 24th, 2013] [Originally Added On: November 10th, 2011]
- BioLogic Stem Cell Therapy - Video [Last Updated On: November 16th, 2011] [Originally Added On: November 16th, 2011]
- BioLogic Stem Cell Therapy - Video [Last Updated On: June 24th, 2013] [Originally Added On: November 16th, 2011]
- AVS Stem Cell Therapy - Video [Last Updated On: June 24th, 2013] [Originally Added On: November 17th, 2011]