As more and more gene therapies are approved, the elements that determine their success depend, increasingly, on the business decisions made early on.
There is nuance to every program but, (across-the-board) the cost of production is a big challenge, Mike Clayman, M.D., CEO and co-founder of Flexion, told BioSpace.
Flexions lead candidate, FX201 (humantakinogene hadenovec), is a case in point. This is an intra-articular gene therapy product for osteoarthritis (OA). It uses a helper-dependent adenovirus (HDAd) vector whose genetic construct the payload is a gene that expresses the interleukin-1 receptor antagonist (IL-1Ra) in the joint to control inflammation.
Inflammation is a known cause of pain, and chronic inflammation is believed to play a key role in the progression of OA, he explained.
FX201 is taken up rapidly by cells lining the joint, converting them into factories to make IL-1Ra. It quells the inflammation and then turns off the gene construct, Clayman said. It has the potential to provide long-term pain relief, functional improvement, and to actually delay the progression of the disease.
By injecting the product directly into the approximately 5 ml volume of the knee joint, he continued, The absolute amount of protein you need to create an effective intra-articular concentration is far less than that which would be needed to achieve systemic therapeutic levels. That translates into what we expect will be much lower doses of FX201, which would reduce manufacturing cost and give us flexibility to charge a price that would still be proportional to value delivered.
The product entered Phase I, a single ascending dose study, this year. Preclinical work suggests that once injected, there is no significant distribution outside the joint.
It is a non-integrating, non-replicating vector, Clayman said. There is preclinical evidence that it delivers meaningful improvement for at least one year, with the slowing of disease progression.
Company scientists believe a single injection FX201 has the potential to provide at least 6 to 12 months of pain relief and functional improvement in addition to possibly slowing disease progression, Clayman said. We believe this product profile, if realized, would represent a transformative new treatment for knee OA.
Currently, Flexion is actively pursuing the possibility of identifying sub-populations of OA patients who may differentially benefit, Clayman said.
The initial study is open broadly to OA patients to evaluate safety and tolerability. Once those data are analyzed, he said subsequent studies will consider and, if possible, incorporate biomarker, phenotypic or genotypic criteria to focus on a more restricted population.
There may be a marker perhaps a serum marker to identify a patient subset that may most benefit from the therapy, Clayman said. With 15 million patients in the U.S. with knee symptoms of OA, and 8 million annual injections to relieve knee pain, it behooves companies to identify a focal population that can most benefit.
But, he acknowledged, The genetics of OA are very complex. Its clearly a multigene disease with additional contributions from environmental and other external factors. Its not as though there are clearly defined genetic subtypes of the disease.
FX201 isnt the first OA product Flexion has developed. Zilretta (triamcinolone acetonide extended-release injectable suspension), an extended-release, intra-articular corticosteroid, was approved by the FDA in 2017 to relieve OA-related knee pain. In Phase III trials, it significantly reduced knee pain for 12 weeks and, for some patients, 16 weeks or more. Since approval, it has completed a Phase IIIb trial for synovitis.
Flexion also is developing FX301 (funapide, a selective sodium channel blocker, formulated in a thermosensitive gel) for acute post-operative pain.
This isnt a gene therapy, Clayman said. This is a peripheral nerve block that is expected to enter the clinic in 2021. The preclinical data so far suggest it may durably prevent post-op pain while preserving motor function.
The FDA and EMA are up-to-speed on gene therapy now. At Claymans meetings with the FDA, We had very robust scientific exchanges. I left impressed with the sophistication that was applied to the discussion. The EMA was similarly sophisticated, he said.
Coincidentally, the criteria for RMAT designation comparable to breakthrough designation for other products illustrating the points for clinical conditions, used OA as the example.
This indicates the FDA is thinking about creative approaches to complex diseases, Clayman said. If we have compelling data, we would not hesitate to pursue RMAT designation.
Flexion already has begun its health economics and outcomes research, modeling this therapeutic in terms of its ability to delay the need for knee replacement (which costs $25,000 to $50,000), and quality of life.
Whether payers will reimburse for gene therapies often depends as much on the price as on delivered value.
Our dose likely will give us manufacturing costs that will allow us to price FX201 much lower than a systemic therapy, which puts us in a better position, Clayman said. Of course, We still must generate compelling data.
Read more from the original source:
Bringing Flexion's OA Gene Therapy to Market Starts with Cost and Benefits in Mind - BioSpace
- Krystal Biotech Inc (KRYS) Reports Strong Q4 and Full Year 2023 Financial Results - Yahoo Finance - February 27th, 2024
- New sickle cell gene therapies are a breakthrough, but solving how to pay their high prices is a struggle - CNBC - February 27th, 2024
- 10 gene therapy companies you should know about - Labiotech.eu - February 27th, 2024
- Former Penn employee sues Gene Therapy Program director, alleging 'unethical and illegal conduct' - The Daily Pennsylvanian - February 27th, 2024
- Gene therapy can't cure deafness because it doesn't need to be cured - The Philadelphia Inquirer - February 27th, 2024
- Fetal surgery expert Tippi MacKenzie shifts to in-utero gene therapy - STAT - February 27th, 2024
- Therapeutic Solutions International Files Patent on Facilitating Effects of JadiCells on Gene Therapy Mediated Cell ... - Business Wire - February 27th, 2024
- CU Anschutz Set to Launch Gene Therapy Trials for Heart Disorder - University of Colorado Anschutz Medical Campus - February 27th, 2024
- ICH targets cell and gene therapies, real-world data as topics ripe for harmonization - Regulatory Focus - February 27th, 2024
- Encoded Therapeutics Announces UK CTA Approval for Dravet Syndrome Gene Therapy Candidate ETX101 - Business Wire - February 27th, 2024
- Voyager Therapeutics Announces Selection of Gene Therapy Development Candidate for Friedreich's Ataxia in ... - GlobeNewswire - February 27th, 2024
- Therapeutic Solutions International Files Patent on Facilitating Effects of JadiCells on Gene Therapy Mediated Cell ... - The Bakersfield Californian - February 27th, 2024
- Ring Therapeutics, a Flagship gene therapy startup, lays off 20% of staff - STAT - February 27th, 2024
- Ed Silverman on new gene therapies, biosimilars, coffee, and more - STAT - STAT - February 27th, 2024
- Combatting HIV using gene therapy - Drug Target Review - February 27th, 2024
- NCDHHS working with federal government on increasing access to sickle cell disease treatment - WECT - February 27th, 2024
- Cell Therapy Weekly: FDA Approves First Cell Therapy For Solid Tumors - RegMedNet - February 27th, 2024
- Rejuvenate Bio Announces Gene Therapy-Mediated Partial Reprogramming Extends Lifespan and Reverses Age ... - Business Wire - February 27th, 2024
- New sickle cell therapy uses gene editing at MUSC | Health | postandcourier.com - The Post and Courier - February 27th, 2024
- Long-term and real-world safety and efficacy of retroviral gene therapy for adenosine deaminase deficiency - Nature.com - February 18th, 2024
- Gene therapy, blood transfusions, stool monitoring: The Sydneysiders trying to escape death - Sydney Morning Herald - February 18th, 2024
- Not too late to repair: gene therapy improves advanced heart failure in animal model - Baylor College of Medicine | BCM - February 18th, 2024
- Direct Administration of CRISPR-Cas9: Tools for Cell and Gene Therapy - Forbes - February 18th, 2024
- Gene therapy's promise seen in its success for AADC deficiency - AADC News - February 18th, 2024
- First Patient Randomized in AskBio Phase II Gene Therapy Trial for Congestive Heart Failure Treatment - Diagnostic and Interventional Cardiology - February 18th, 2024
- FDA to review expanded use of Sarepta Duchenne gene therapy - Yahoo Finance - February 18th, 2024
- How gene therapy can help treat a rare blood disorder - KUTV 2News - February 18th, 2024
- CRISPR gene therapy Casgevy secures approval in Europe - Pharmaceutical Technology - February 18th, 2024
- FDA Updates for the Week of Feb. 12, 2024: New Approvals, an Extended Review and Goal Dates Set - Managed Healthcare Executive - February 18th, 2024
- First Patient Randomized in AskBio Phase II Gene Therapy Trial for Congestive Heart Failure - Business Wire - February 18th, 2024
- Lisa Jarvis: A cure for some kinds of hearing loss? Gene therapies are getting closer - St. Paul Pioneer Press - February 18th, 2024
- Spinal Muscular Atrophy Market: Navigating Therapeutic Advances towards USD 5.6 Billion by 2034, with a CAGR of ... - Yahoo Finance - February 18th, 2024
- Crispr Therapeutics' Gene Therapy Wins EU Approval - TipRanks.com - TipRanks - February 18th, 2024
- Revolutionizing Gene Therapy: A Novel Technique for In Vivo CAR T Cells - Medriva - February 18th, 2024
- How Stella Vnook is 'infusing innovation' into cell therapies with Likarda's technology - BioPharma-Reporter.com - February 18th, 2024
- Using cancer's 'superpower' to boost T-cell therapies in mice - FierceBiotech - February 18th, 2024
- Parkinson's Disease Patient Identification and Education Will Need to Improve When New Disease Modifying ... - Yahoo Finance - February 18th, 2024
- CRISPR (CRSP) to Report Q4 Earnings: What's in the Cards? - Yahoo Finance - February 18th, 2024
- Gene Therapy: A Ray of Hope for Heart Failure Treatment | Health News - Medriva - February 18th, 2024
- Gene therapy trials restore hearing to children born deaf - The Hill - February 2nd, 2024
- Early Trial Success for Inherited Deafness Gene-Therapy - RegMedNet - February 2nd, 2024
- Sickle cell gene therapy first focus of Medicaid pay model - Modern Healthcare - February 2nd, 2024
- Beyond chemotherapy: Navigating the promise and perils of CAR-T therapy in pediatric cancer - BioPharma-Reporter.com - February 2nd, 2024
- Angiodema: Gene therapy blocks painful hereditary disorder - BBC - February 2nd, 2024
- FDA: Genome editing therapies may use accelerated approval pathway - Regulatory Focus - February 2nd, 2024
- CRISPR tech treats severe hereditary condition successfully - Interesting Engineering - February 2nd, 2024
- Gene Therapy Restores Hearing in Small Trial for Kids With Hereditary Deafness - Technology Networks - February 2nd, 2024
- Gene-based therapy may slow development of life-threatening heart condition - Medical Xpress - February 2nd, 2024
- Jaguar Gene Therapy Announces FDA Clearance of IND to Study JAG201 in a Genetic Form of Autism Spectrum ... - Business Wire - February 2nd, 2024
- Replacing the PKP2 gene prolongs survival in ARVC patients - Drug Target Review - February 2nd, 2024
- Cell and gene therapies top pharmaceutical industry trend to watch for 2024 - Pharmaceutical Technology - February 2nd, 2024
- Gene Therapy Restores Hearing in Children with Hereditary Deafness - The Hearing Review - February 2nd, 2024
- 2 Dutch among 10 "functionally cured" of hereditary swelling disease by new gene therapy - NL Times - February 2nd, 2024
- FDA publishes final industry guidance for CAR-T and gene therapies - PMLiVE - February 2nd, 2024
- Gene therapy cures hereditary deafness in two people - Advanced Science News - February 2nd, 2024
- Hearing Restored in Deaf Children in Gene Therapy Clinical Trial - Securities.io - February 2nd, 2024
- Vivet Therapeutics Receive 4.9 Million to Advance Development of Gene Therapy - European Pharmaceutical Manufacturer - February 2nd, 2024
- Adverum Biotechnologies will Host Webcast to Review LUNA Phase 2 Preliminary Efficacy and Safety Results on ... - GlobeNewswire - February 2nd, 2024
- Allogene parks Notch CARs, leaving one on the road - FierceBiotech - February 2nd, 2024
- Experimental gene therapy allows kids with inherited deafness to hear - The Associated Press - January 25th, 2024
- Gene-therapy breakthrough allows congenitally deaf children to hear Harvard Gazette - Harvard Gazette - January 25th, 2024
- Gene therapies restore hearing in several kids with inherited deafness - Livescience.com - January 25th, 2024
- Boy born deaf can hear for the first time thanks to a gene therapy procedure - NBC 6 South Florida - January 25th, 2024
- Gene therapy restores hearing in children with hereditary deafness - Medical Xpress - January 25th, 2024
- Children's Hospital of Philadelphia Performs First in U.S. Gene Therapy Procedure to Treat Genetic Hearing Loss - PR Newswire - January 25th, 2024
- Children's Hospital of Philadelphia uses gene therapy to help 11-year-old boy hear for 1st time - WPVI-TV - January 25th, 2024
- Breakthrough gene therapy treatment restores hearing in children born deaf - The Independent - January 25th, 2024
- Gene Therapy Administered Via Virus Cures Deafness in 11-Year-Old Boy - Futurism - January 25th, 2024
- 11-Year-Old Boy Hears For First Time Ever Thanks To Gene Therapy Breakthrough - IFLScience - January 25th, 2024
- Gene Therapy Deafness | National | caledonianrecord.com - The Caledonian-Record - January 25th, 2024
- Sickle cell gene therapy to be covered by Blue Cross insurers - Modern Healthcare - January 25th, 2024
- Experimental gene therapy allows kids with inherited deafness to hear - Jackson Hole News&Guide - January 25th, 2024
- Gene therapy allows 11-year-old boy to hear for the first time - Latest From ITV News - ITVX - January 25th, 2024
- Experimental Gene Therapy Allows Kids With Inherited Deafness To Hear - Southern Minnesota News - January 25th, 2024
- Joint US-China gene therapy trials restore hearing in 5 kids, a first - Interesting Engineering - January 25th, 2024
- Gene Therapy Deafness | Nation | The Daily News - Galveston County Daily News - January 25th, 2024
- In Draft Guidance for Cell and Gene Therapy Industry, FDA Broadens its Approach to Product Potency - Precision Medicine Online - January 25th, 2024
- Gene therapy helps restore hearing in children with hereditary deafness - Shropshire Star - January 25th, 2024
- Gene therapy breakthrough enables deaf boy to hear for the first time - The Week - January 25th, 2024
- FDA eyes collaborative review pilot for gene therapies - Regulatory Focus - January 17th, 2024