As activity in this space grows, so do the hurdles in moving these products forward.
Cell and gene therapy (CGT)its risks and promisesare succinctly summarized in this description of clinical trial number NCT01129544, a Phase I/II study in children born with X-linked severe combined immunodeficiency (SCID-X1), an inherited, rare, and life-threatening disease. The eight-person trial, which began in May 2010, continues today. The following paragraph has been edited.1
Gene transfer is still research for two reasons. One, not enough children have been studied to tell if the procedure is consistently successful. [And] we are still learning about its side effects and doing gene transfer safely. In previous trials, five children developed gene transfer-related leukemia; four are in remission; one died.
If the above information has stifled the research communitys scientific curiosity about CGT, it is not evident. Evidence from numerous sourcesClinicalTrials.gov, the Alliance for Regenerative Medicine (ARM), FDAare chock-a-block with studies, trials, and figures showing these therapies popularity. In the second quarter of 2022, 3,633 such treatments were in development, up from 1,745 in May 2021. The vast majority are in the preclinical stage.2,3
Some sources are revealing more.
Most indicate that academics now have a remarkable presence in the CGT development space, including sponsorship. Last year, for the first time, ARM included sponsorship figures in its twice-annual industry report.4 Academic- and government-sponsored trials far exceeded industry for sponsored trials in CGT. Stephen Majors, senior director for public affairs, ARM, says the alliance knew of academias presence for the past few years, but only was able to get data this year from its partner, Global Data.
Less reliable, but still noteworthy, are data from ClinicalTrials.gov: for active Phase I trials, industry has 89; others, which covers academia and government, have 50. Industry enrollment for Phase I is 172; others, 116.Phase III is one for others, eight for industry.
A little disruption in pharmas corner of the world? It seems that way. While basic bench to preclinical to clinical trial has long been the traditional route to FDA approvaland no one interviewed for this article suggested a reroutewhat it does imply is that pharma members have some competition from the spin-offs and academic biotechs that historically they have absorbed.
There are suspected trends that we are watching, says Majors.As to whether academias presence in this spot can be called a trend depends on ones definition of what a trend is. The Centers for Disease Control and Prevention (CDC) considers changes over a number years to determine a trend; financial investment firms typically evaluate over a two-year period.Considering that CGT companies raised $23.1 billion in 2021, 16% more than 2020,3 the answer to the above question could be, maybe.
The CGT space is still immature, according to Mike Rea, founder of Protodigm, a self-described exploratory research organization that partners with biopharma clients on alternative development and commercial solutions. Physicians need time to be comfortable with these therapies, notes Rea, so they may not be used on a regular basis.
For example, physicians have to understand how to deliver the gene, agrees cardiologist Arthur M. Feldman, MD, PhD, whose lab worked on a heart failure-related mutation in BAG3 for decades.
Last month, the company he founded, Renovacor, agreed to be acquired by Rocket Pharmaceuticals.5 We are asking physicians to do something they never did before and to understand a very different set of information, including risk/benefit discussions that they didnt learn about in medical school, he says. Feldman is a Laura H. Carnell Professor of Medicine, Division of Cardiology, and a member of the Center for Neurovirology and Gene Editing at the Lewis Katz School of Medicine at Temple University.
Chris Learn, Parexels vice president of cell and gene therapy, is unequivocal regarding academias increased presence in the drug development space focused around these treatments. He cites MD Anderson and Moffitt Cancer Center as two institutions that are sponsoring their own trials. The lines are really blurring here, he tells Applied Clinical Trials. It is indisputable.
The following is a look at how academia is showing up in various reports.
In its 2022 report4, ARM separated sponsorship, type of therapygene, cell-based, and tissue engineeringand trial phase. What these data show are industry far exceeding academic and government sponsored trials for gene therapy, while for cell therapy alone, the reverse is true: 656 cell therapy trials for academic and government, and 424 for industry. For gene therapy, there are 84 for the academics and government, and 222 for industry. In a later report, ARM found non-industry trials dropped.
Pharma Intelligences Pharma R&D Annual Review does not break down trials by their sponsors. It does, however, break down whats in the pipeline in various categories, including by the number of therapies per company, and by disease type.6 In numbers captured prior to March 2020, the analysis reported 1,849 companies with asingle drug in its pipeline, up from 1,633 in 2019, comprising more than half of all drug companies. As for types of therapies, gene therapy was in third place, the same spot it occupied in 2019. (Cancer-related therapies occupy the top spots.) Overall, biotech therapies in the pipeline increased by 13.2% in 2020 over 20196,135 vs. 5,422. Cellular therapy, the field in which academia is dominating, rose to 14th place, up from 33.
In 1982, Feldman was a resident in the cardiac care unit at the Johns Hopkins Hospital in Baltimore when he took care of a 22-year-old woman, a native Pennsylvanian, who was dying of heart failure. Sadly, we didnt have drugs with which to treat her, he recalls. Feldmans involvement with the case and the womans family led to his career as a cardiologist, he says. Twenty years later in Philadelphia, he was asked to see a heart-failure patient in consult, who turned out to be the aunt of the younger woman. It would take almost another 10 years until the technology became available to identify the genomic anomaly in this family. Here, a genetic variant that is produced by one of two alleles causes the protein product to be unstable. The result: the cell removes it, so the person with the variant has just half the amount of required protein.
BAG3 is an interesting protein that is found in the heart, the skeletal muscles, and the nervous system, including the brain. Its function is to help remove degraded and misfolded proteins, stop apoptosis or programmed cell death, and maintain the structure of the skeletal muscles. A missing allele isnt the only genetic cause for heart failure, Feldman said. Other patients, while having the correct amount of DNA, have a point mutationa single amino acidin half of the produced DNA. That single letter is the wrong amino acid in the specific site in the protein.
Around this time, Kamel Khalili, PhD, Laura H. Carnell Professor, and chair of the department of microbiology, immunology, and inflammation; director of the Center for Neurovirology and Gene Editing; and director of the Comprehensive NeuroAIDS Center, Lewis Katz School of Medicine, Temple University, had created a method by which he could excise the HIV virus from patients using the new technique of CRISPR-Cas9.
Khalili believes that BAG3 may be involved in the pathogenesis of HIV-1 in brain diseases and protein quality control caused by viral infection as well as several other disorders, including Alzheimers disease and dementia. BAG3 changes the homeostasis of the cell, he says. The only solution is to fix the cell. Khalili has used CRISPR technology to excise the viral genome in both small and large investigational animals and has recently started a Phase I trial to test the safety of the new gene-editing treatment. Khalili, too, started a company, but Temple holds the license. In the case of Renovacor, it was granted the license by Temple.
As a scientist, when you are doing something in biomed research, [the] goal is to translate bench work to the clinic for [the] wellness of people. We are doing long hours and long days because we want to help. We are trying to see if discovery can help people, says Khalili. I know my limit, I stop at business aspects. My interest is to discover research which can help populations.
Was Feldman happy with his business experience? As a company gets bigger, others join the team who fulfill other roles, like acquiring funding or developing the actual product, he says. Releasing the control reins are difficult. But if it speeds up the timeline to get an approved product into the clinic, then its all worth it, he adds.
Researchers such as Feldman and Khalili, says Kaspar Mossman, PhD, director of communications and marketing at QB3, a University of California biotech accelerator, are normally not deeply interested in business. He notes the new flagship space in UC Berkeley called Bakar Lab. So far, it has 25 companies, one-third from university labs. They collaborate, they share equipment, [at times] they merge, Mossman tells Applied Clinical Trials.
And, he adds, Academics tend to be very smart individuals. The more time they spend in business, they learn stuff and become serial founders, says Mossman. They are honest about not wanting to be a CEO.
In terms of business, the academics employers are also pretty smart. The huge bugaboo with CGT commercialization is the manufacturing processthe need for an apheresis unit, ultra-cold storage, and regulated cell processing facilities.
Some institutions are building their own manufacturing facilities to more easily meet the increasingly complicated standards pertaining to regenerative medicine production. Harvard, MD Anderson, Moffitt, the University of Pennsylvania, and the University Hospital of Liege in Belgium8 all have or are planning to build their own facilities.
As for how academias presence impacts the traditional pharma space, those interviewed cited pros and cons. More research is better, more companies vying for venture capital funding is not. But more trials mean more competition among similar therapies, which, says Majors, is a good thing.
We need experimentation, adds Rea. If left to pharma, he says, the research wouldnt happen. Smaller biotechs are taking the risk. Over the last 10 years, Rea believes pharma has been slow in the risk-taking department. Once upon a time, pharma didnt have many competitors. Now, with many numerous smaller companies with viable assets, willing to accept a smaller net profit, the competition is creating some angst. Pharma cant project everyones movement, says Rea. The gene/cell therapy landscape [for products] is huge.
Likely adding to the angst: Those smaller biotechs are getting financial help. Between April 4, 2021, and June 24, 2021, of 23 start-up financing deals, 19 involved academics.2
Learns viewpoint is different. He says there are too many players out there, and while large pharma may be averse to risk, I really do believe what we are witnessing are simply market forces that have played into this. There is so much cash coming in, he continues, that people can be blinded by the pitfalls. The CGT area, he adds, is bloated and he says the industry needs an overall strategy.
Learn doesnt think that academias presence in the CGT space is a flash in the proverbial pan. The enthusiasm to find cures is real, and some research institutions have the endowments to see the trials through. I think it is just the beginning, says Learn. Academia will put their futures in front of them. Why put all your sweat equity into it and not have any fiduciary benefit of the approved product?
In Pharma Intelligences 2020 Pharma R&D Review, its author questioned the wisdom of so many drugs, overall, in the pipeline4,001 added in 2018 and 4,730 added in 2019, for a total of 17,737 drug candidates. [A]re the industrys eyes getting too big for its belly? Unless it can continue to provide [approved therapies] then a certain degree of control in the pipeline might be advisable, the report stated.6
And now to costs. While no one doubts these cures change lives, the question of access persists. FDAs approval of Bluebird Bios second therapy this year, branded as Skysona, for early but active cerebral adrenoleukodystrophy, is expected to cost $3 million. Learn doubts that payers are jumping up and down to get Skysona on their formularies.
Its still a fairly dicey business proposition for companies to invest in this field, Steven Pearson, MD, president of the Institute for Clinical and Economic Review (ICER), said recently.8Theres still a risk that next-generation therapies will not flourish even in developed countries health systems, he added.
One positive development in the US, however, occurred late last month when Congress reauthorized the Prescription Drug User Fee Act (PDUFA) for the next five years, 2023-2027. The action maintained FDAs authority to collect fees from manufacturers and keep and recruit agency staff to review the increased number of CGT applications. Majors says most of FDAs review of CGT products involves scalability and consistent reproducibility in the manufacturing process, which, of course, means traveling.
According to a Senate press release9, FDA is seeking to hire at least 320 new staff members. In a statement, Pharmaceutical Research and Manufacturers of America (PhRMA) said a modern regulatory framework supported by PDUFA helps ensure patients have timely access to lifesaving medicines.
PDUFA reauthorization aside, there is little argument that the field of CGT, from research and drug discovery through commercialization, is advancing rapidly. In turn, so are the unique operational and manufacturing challenges that these therapies present. This reality may thin the currently crowded playing field in CGT going forward, with those sponsors and partners best prepared to deliver on the numerous touchpoints required separating from the pack.
Christine Bahls, Freelance Writer for Medical, Clinical Trials, and Pharma Information
Continue reading here:
The Risk-Reward Proposition for CGT Clinical Trials - Applied Clinical Trials Online
- BENITEC BIOPHARMA INC. Management's Discussion and Analysis of Financial Condition and Results of Operations (form 10-Q) - Marketscreener.com - February 13th, 2023 [February 13th, 2023]
- CENTOGENE to Participate in Upcoming Conferences in February in the Lead Up to Rare Disease Day - Marketscreener.com - February 7th, 2023 [February 7th, 2023]
- Gene | Definition, Structure, Expression, & Facts | Britannica - January 27th, 2023 [January 27th, 2023]
- New gene therapy delivers treatment directly to brain - January 27th, 2023 [January 27th, 2023]
- Indian Pharma Congress: Gene-cell therapy, preventive medicine future of health care, says expert - Economic Times - January 25th, 2023 [January 25th, 2023]
- A blood test that identifies people at higher risk of miscarriage? Thats the goal of this award-winning Rutgers med student. - The Philadelphia... - January 19th, 2023 [January 19th, 2023]
- Gene Therapy: Genes As Medicine | Pfizer - January 6th, 2023 [January 6th, 2023]
- How Genomics will ensure a risk-free and beneficial treatment for good health and well-being - The Financial Express - December 28th, 2022 [December 28th, 2022]
- Regenerative Medicine Advanced Therapy Designation | FDA - December 18th, 2022 [December 18th, 2022]
- 3576 - Gene ResultCXCL8 C-X-C motif chemokine ligand 8 [ (human)] - November 23rd, 2022 [November 23rd, 2022]
- Study identifies new gene that drives colon cancer - EurekAlert - October 17th, 2022 [October 17th, 2022]
- Updated Stroke Gene Panels: Rapid evolution of knowledge on monogenic causes of stroke | European Journal of Human Genetics - Nature.com - October 17th, 2022 [October 17th, 2022]
- The challenges of translating CRISPR to the clinic - Labiotech.eu - October 17th, 2022 [October 17th, 2022]
- Editas Medicine Presents Preclinical Data on EDIT-103 for Rhodopsin-associated Autosomal Dominant Retinitis Pigmentosa at the European Society of Gene... - October 17th, 2022 [October 17th, 2022]
- 'We have to find a way': FDA seeks solutions to aid bespoke gene therapy - BioPharma Dive - October 17th, 2022 [October 17th, 2022]
- Mathematical model could bring us closer to effective stem cell therapies - Michigan Medicine - October 17th, 2022 [October 17th, 2022]
- Approval, Commercialization Highlighted at Cell & Gene Meeting on the Mesa - Genetic Engineering & Biotechnology News - October 17th, 2022 [October 17th, 2022]
- CANbridge-UMass Chan Medical School Gene Therapy Research in Oral Presentation at the European Society of Gene and Cell Therapy (ESGCT) 29th Annual... - October 17th, 2022 [October 17th, 2022]
- Depression Treatment: How Genetic Testing Can Help Find the Right Medication - Dunya News - October 17th, 2022 [October 17th, 2022]
- Precision Medicine Could Get Even More Precise With Allarity Therapeutics Next-Generation Diagnostics - Benzinga - October 17th, 2022 [October 17th, 2022]
- Decibel Therapeutics Receives FDA Clearance of IND Application for DB-OTO, a Gene Therapy Product Candidate Designed to Provide Hearing to Individuals... - October 17th, 2022 [October 17th, 2022]
- Time for your medicine: unlocking the power of our body clocks - The Guardian - October 17th, 2022 [October 17th, 2022]
- Replay establishes distinguished Scientific Advisory Board of genomic medicine and cell therapy experts - Yahoo Finance - October 17th, 2022 [October 17th, 2022]
- Scientists Reappraise the Role of Zombie Cells That Anti-aging Medicine Has Sought to Eliminate - Neuroscience News - October 17th, 2022 [October 17th, 2022]
- Forge Biologics Announces Updated Positive Clinical Data in RESKUE, a Novel Phase 1/2 Gene Therapy Trial for Patients with Krabbe Disease - Business... - October 17th, 2022 [October 17th, 2022]
- Gene Expression Signatures Are Analyzed for Biomarkers of Response in HCC - Targeted Oncology - October 17th, 2022 [October 17th, 2022]
- NHS England World-first national genetic testing service to deliver rapid life-saving checks for babies and kids - NHS England - October 17th, 2022 [October 17th, 2022]
- The proteinprotein relationship that could mend a broken heart - RegMedNet - October 17th, 2022 [October 17th, 2022]
- Study finds microprotein correlated to Alzheimers risk - Daily Trojan Online - October 11th, 2022 [October 11th, 2022]
- Passage Bio Announces Appointment of William Chou, M.D. as Chief Executive Officer - Yahoo Finance - October 11th, 2022 [October 11th, 2022]
- Gene Therapy Rapidly Improves Night Vision in Adults with Congenital Blindness - Newswise - October 11th, 2022 [October 11th, 2022]
- Scientists Discover Protein Partners that Could Heal Heart Muscle | Newsroom - UNC Health and UNC School of Medicine - October 11th, 2022 [October 11th, 2022]
- The Pros and Cons of Lentiviral and Adeno-Associated Viral Vectors - The Medicine Maker - October 11th, 2022 [October 11th, 2022]
- Insights & Outcomes: Foreign DNA, quantum potholes and relapsing fever - Yale News - October 11th, 2022 [October 11th, 2022]
- Expediting IND applications with drug master files - BioPharma Dive - October 11th, 2022 [October 11th, 2022]
- UNC School of Medicine Awarded $3 Million to Lead Study to Reduce PTSD Frequency, Severity | Newsroom - UNC Health and UNC School of Medicine - October 11th, 2022 [October 11th, 2022]
- Lineage to Present at Alliance for Regenerative Medicine 2022 Cell & Gene Meeting on the Mesa - businesswire.com - October 8th, 2022 [October 8th, 2022]
- The Next Crispr Gene Editing IPO Could Be Near - Henry Herald - October 8th, 2022 [October 8th, 2022]
- 10-year CRISPR anniversary: How gene editing revolutionized medicine, and what lies ahead - Genetic Literacy Project - October 8th, 2022 [October 8th, 2022]
- Blood from a baby at birth can be gene sequenced to prevent diseases - USA TODAY - October 8th, 2022 [October 8th, 2022]
- What doctors wish patients knew about breast-cancer prevention - American Medical Association - October 8th, 2022 [October 8th, 2022]
- Growth in Cell and Gene Therapy Market - Pharmaceutical Technology Magazine - October 8th, 2022 [October 8th, 2022]
- Gene Editing Service Market 2022 : Top Players to Reflect Impressive Growth Rate till 2029: Caribou Biosciences, CRISPR Therapeutics, Merck KGaA,... - October 8th, 2022 [October 8th, 2022]
- Tip Sheet: $78 million to support new precision oncology institute, update on experimental gene therapy for herpes and the launch of Fred Hutch's new... - October 8th, 2022 [October 8th, 2022]
- Cell and Gene Therapy: Rewriting the Future of Medicine - Technology Networks - October 2nd, 2022 [October 2nd, 2022]
- Growth in Cell and Gene Therapy Market - BioPharm International - October 2nd, 2022 [October 2nd, 2022]
- CRISPR Therapeutics Announces FDA Regenerative Medicine Advanced Therapy (RMAT) Designation Granted to CTX130 for the Treatment of Cutaneous T-Cell... - October 2nd, 2022 [October 2nd, 2022]
- BioMarin Resubmits Biologics License Application (BLA) for Valoctocogene Roxaparvovec AAV Gene Therapy for Severe Hemophilia A to the FDA - PR... - October 2nd, 2022 [October 2nd, 2022]
- Fighting Breast and Ovarian Cancer With a Lupus Antibody - Yale School of Medicine - October 2nd, 2022 [October 2nd, 2022]
- This gene therapy company is testing new tech to 'switch off' diabetes and obesity with a pill - Euronews - October 2nd, 2022 [October 2nd, 2022]
- Tenaya Therapeutics to Participate in Inaugural Hypertrophic Cardiomyopathy Medical Societys 2022 Scientific Sessions - Yahoo Finance - October 2nd, 2022 [October 2nd, 2022]
- Risk of Alzheimer's dementia may be predicted with help of new tool Washington University School of Medicine in St. Louis - Washington University... - October 2nd, 2022 [October 2nd, 2022]
- Tiny Sea Creature's Genes Shed Light on Evolution of Immunity - UPMC - October 2nd, 2022 [October 2nd, 2022]
- Who will get the call from Stockholm? It's time for STAT's 2022 Nobel Prize predictions - STAT - October 2nd, 2022 [October 2nd, 2022]
- Excision BioTherapeutics Awarded California Institute for Regenerative Medicine (CIRM) Grant to Support Ongoing Phase 1/2 Trial Evaluating EBT-101 as... - October 2nd, 2022 [October 2nd, 2022]
- NeuroVoices: Emma Ciafaloni, MD, on the Vast Expansion of Innovative Approaches to Duchenne Muscular Dystrophy - Neurology Live - October 2nd, 2022 [October 2nd, 2022]
- COVID mRNA Jabs and Testing Kicked Off This Industry of Drug Development: Here's What You Need to Know - The Epoch Times - October 2nd, 2022 [October 2nd, 2022]
- Kidney resident macrophages have distinct subpopulations and occupy distinct microenvironments - University of Alabama at Birmingham - October 2nd, 2022 [October 2nd, 2022]
- Nobel Prize for medicine: the full list of winners - The National - October 2nd, 2022 [October 2nd, 2022]
- The surprising link between circadian disruption and cancer may have to do with temperature - EurekAlert - October 2nd, 2022 [October 2nd, 2022]
- The global live cell imaging market is expected to grow at a CAGR of 8.44% during 2022-2027 - Yahoo Finance - October 2nd, 2022 [October 2nd, 2022]
- Chroma Medicine Announces Formation of Scientific Advisory Board of Global Experts in Gene Editing and Cell and Gene Therapy - PR Newswire - September 20th, 2022 [September 20th, 2022]
- Ring Therapeutics Announces Issuance of U.S. Patent for its Anellovector Compositions - Yahoo Finance - September 20th, 2022 [September 20th, 2022]
- Cholesterol gene mutation: Why would a healthy 27-year-old have severe heart problems? - 69News WFMZ-TV - September 20th, 2022 [September 20th, 2022]
- Gene Therapy for Severe Hemophilia B Could Be More Cost Effective Than Current Treatments - Managed Healthcare Executive - September 20th, 2022 [September 20th, 2022]
- AVROBIO Receives Rare Pediatric Disease Designation from U.S. Food and Drug Administration (FDA) for First Gene Therapy in Development for Cystinosis... - September 20th, 2022 [September 20th, 2022]
- The Biggest CGT Breakthroughs Through the Eyes of Our 2022 Power List - The Medicine Maker - September 20th, 2022 [September 20th, 2022]
- Leading Virus Researcher to Chair UVA's Department of Microbiology, Immunology and Cancer Biology - UVA Health Newsroom - September 20th, 2022 [September 20th, 2022]
- Work remains on Tay-Sachs and other Ashkenazi genetic disorders J. - The Jewish News of Northern California - September 20th, 2022 [September 20th, 2022]
- Study Shows Genetic Link to Moving to the Beat of Music - Newswise - September 20th, 2022 [September 20th, 2022]
- Viewpoint: In the post Roe v Wade world, what changes should a biology textbook writer make to address the medical repercussions of Dobbs? - Genetic... - September 20th, 2022 [September 20th, 2022]
- Alnylam Receives Approval in Europe for AMVUTTRA (vutrisiran) for the Treatment of Hereditary Transthyretin-mediated (hATTR) Amyloidosis in Adult... - September 20th, 2022 [September 20th, 2022]
- CSL flexes gene therapy muscle with latest drug - Sydney Morning Herald - September 20th, 2022 [September 20th, 2022]
- The MIT Press releases new book on the science of the heart from cardiac expert Dr. Sian Harding - EurekAlert - September 20th, 2022 [September 20th, 2022]
- Global Pharmaceutical Contract Manufacturing Market is projected to reach a market value of US$329.7 Billion in 2032: Visiongain Reports Ltd - Yahoo... - September 20th, 2022 [September 20th, 2022]
- Alzheon Reports Industry-Leading Biomarker, Brain Preservation and Clinical Effects Following 12 Months of Treatment in Phase 2 Trial of Oral ALZ-801... - September 20th, 2022 [September 20th, 2022]
- Do You Have Lung Cancer With An EGFR Mutation? If So, The Drug Tagrisso Might Be Right For You Based On New Results From A 'Practice Changing' Trial -... - September 20th, 2022 [September 20th, 2022]
- Getting rid of unwanted transformed cells: Possible new directions in cancer therapy - EurekAlert - September 20th, 2022 [September 20th, 2022]
- Sven Kili on reconvening with the ISCT - The Medicine Maker - September 14th, 2022 [September 14th, 2022]
- Study refutes long-held belief that the Corin gene causes hypertension in African Americans - University of Alabama at Birmingham - September 14th, 2022 [September 14th, 2022]