The first ever approval of a new kind of cancer immunotherapy called CAR-T is one step closer. A 10-member panel of doctors and researchers who advise the Food and Drug Administration recommended with a rare unanimous vote that the agency approve a treatment for kids and young adults with a severe form of leukemia who have run out of other options.
The therapy would involve genetically modifying a patients T cells to kill cancer and then infusing them back into the body. The dramatic effect of the treatment, known for years as CTL-019, was never questioned at the meeting. Of 68 young people receiving it, 52 of them had an excellent response almost immediately, with their cancer disappearing within the first three months. Three-quarters of those patients remained cancer-free six months after treatment.
Explaining their vote, many advisors were effusive. Its the most exciting thing Ive seen in my lifetime, said Timothy Cripe, a blood cancer and bone marrow transplant specialist at Nationwide Childrens Hospital in Columbus, OH.
Others had high praise for the drugs marketer, Novartis (NYSE: NVS), and its plans to keep a close eye on the potentially severe side effects of CAR-T if it becomes a commercial product. Those so-called risk mitigation plans were one of the main concerns that the FDA, in documents released Monday, asked its advisors to consider.
The main side effect of CTL-019 is cytokine release syndrome, a blistering immune reaction to the drug and the detritus of dying cancer cells. It can be deadly, with spiking fevers and other symptoms, if medical staff arent properly trained for it. Novartis said it would train staffers at 30 to 35 medical centers and take other measures, as well.
At the FDAs behest, the advisory panel spent much of the day discussing long-term side effects, toothe possibility that the T cell modification could go awry, and years down the road cause secondary cancers. Its a concern that stems from the early days of gene therapy, when the genetic tweaking of patients cells with a modified virus turned on cancer-causing genes.
Novartis officials said they would follow patients for at least 15 years and investigate any cases of secondary cancers. Committee member Catherine Bollard, who runs an immunotherapy center at the Childrens Research Institute in Washington, DC, said she would like Novartis also to investigate when patients relapse with altered forms of leukemia.
The committee members said it was hard to assess the long-term risk, but in patients with no other treatment options, the near-term benefits of CAR-T therapy more than tipped the scales. You have to be a long-term survivor to experience [long-term] toxicity, said Bruce Roth of the Washington University School of Medicine in St. Louis, MO. CTL-019 should give kids with ALL a chance for long-term survival, he said.
In a field that has plenty of pressing questions about severe, even deadly short-term side effects including brain swelling that was seen in trials of CAR-T therapies run by competing companies many observers were left wondering why the FDA highlighted the long-term risks of the CAR-T causing another cancer, perhaps years into the future. One possibility is that the agency is anticipating that CAR-T products will be developed for patients who arent at the end of the line. For example, the engineered T cells could be used as an adjuvant or additional therapy after a previous treatment has wiped out all but the last traces of cancer, said Richard Maziarz, a blood cancer specialist at Oregon Health and Science University in Portland.
In those settings, the downstream effect [of triggering a secondary cancer] is conceivable, said Maziarz. (Maziarz was not part of todays advisory committee. He has treated adult patients with CTL-019 as part of a different Novartis study.)
The news today buoyed Novartis stock, which was up $1.22, or nearly 1.5 percent. Based in Switzerland, but with much of its R&D in the U.S., Novartis was the first biopharma group to dive into the CAR-T field in a big way when in 2012 it launched a collaboration with the University of Pennsylvania. Much of the early work on CTL-019, now renamed tisagenlecleucel, took place in the universitys labs and clinics.
Novartis disbanded its cell and gene therapy group last year but vowed to press on with CTL-019. Approval in pediatric ALL now seems all but assured; the FDA rarely bucks the advice of its advisory committees. Novartis is also vying to have CTL-019 approved to treat adults with the most common forms of non-Hodgkin lymphoma. Beyond that, the companys plans with CAR-T are unclear. Penn has a next-generation CAR-T under development, dubbed CTL-119, which is not licensed to Novartis.
Novartis also convinced the advisory committee that its complicated manufacturing process could be fast and consistent. There are many links in the production chain, which requires extracting T cells from a patient, shipping them to a lab for genetic modification, making viral vectors that insert new DNA into the T cells, then shipping the cells back to be dripped through an IV back into the patient.
Such a complex system for making personalized treatments is likely to drive up their cost, and the next big hurdle (assuming an FDA approval this fall) is to win over insurers. The complexity can also introduce other kinds of risk, such as failure of the cells to repopulate the patients immune system. I think it will be important in the commercial phase to assess both failure rates and turnaround times for CAR-T production, said Krishna Komanduri, director of the Sylvester Comprehensive Cancer Center Adult Stem Cell Transplant Program at the University of Miami, who has treated patients with other experimental CAR-Ts, but not the one from Novartis. Either delays or failure of production will have clinical consequences for the highest risk patients.
Photo by Guido Van Nispen via Creative Commons 2.0 license.
Alex Lash is Xconomy's National Biotech Editor. He is based in San Francisco.
- Newborn in Japan receives first treatment with liver STEM cells - ZME Science - May 23rd, 2020
- Adult Stem Cells Market with Coronavirus (Covid-19) Impact Analysis | Industry Strong Development By Major Eminent Players, New Innovations, Key... - May 16th, 2020
- Stem Cell and Regenerative Therapy Market Covid-19 Impact Analysis, Size, Share & Trends Analysis Report by Component, By Enterprise Size, By End... - May 16th, 2020
- The RNA binding protein CPEB2 regulates hormone sensing in mammary gland development and luminal breast cancer - Science Advances - May 16th, 2020
- Stem Cells Market Market Developments and Analysis (impact of Covid-19) 2020-2026 - Herald Writeup - May 15th, 2020
- Takeda Pharmaceutical : China announces ADCETRIS (brentuximab vedotin) is approved for the treatment of adult patients with CD30-positive Lymphomas -... - May 15th, 2020
- New Data for Investigational CRISPR/Cas9 Gene-Editing Therapy CTX001 for Severe Hemoglobinopathies Accepted for Oral Presentation at the 25th European... - May 14th, 2020
- Dlp-mediated Hh and Wnt signaling interdependence is critical in the niche for germline stem cell progeny differentiation - Science Advances - May 14th, 2020
- Little Skates Could Hold the Key to Cartilage Therapy in Humans - Technology Networks - May 14th, 2020
- Strides in Medical Tourism Market Key Driver of Low-cost Patient Care in Globalized Healthcare Systems, Notes TMR - PR Newswire UK - May 14th, 2020
- Australia's Mesoblast raises $90M to scale up stem cell therapy manufacturing to treat COVID-19 ARDS - BioWorld Online - May 14th, 2020
- CTX001 for Treatment of Sickle Cell Disease and Other Blood Disorders - Sickle Cell Anemia News - May 14th, 2020
- Stem cells therapy A prospective treatment against coronavirus? - Daily Excelsior - May 14th, 2020
- Protocol Management, Off-the-Shelf Therapies Help Bring CAR T Into More Settings - Targeted Oncology - May 13th, 2020
- BrainStorm Leases a New Cleanroom Facility at The Tel Aviv Sourasky Medical Center to Manufacture NurOwn for The European Union - Yahoo Finance - May 13th, 2020
- CRISPR Therapeutics and Vertex Pharmaceuticals Announce FDA Regenerative Medicine Advanced Therapy (RMAT) Designation Granted to CTX001 for the... - May 13th, 2020
- Study: Want to lose weight? Get rid of that pesky nose - The Big Smoke Australia - May 13th, 2020
- Region 3: Immune and Cellular Tx, Part II - MedPage Today - May 9th, 2020
- Rituximab Offers No Extra Benefit to Induction Chemo in ALL - Medscape - May 9th, 2020
- ROCKET PHARMACEUTICALS : Management's Discussion and Analysis of Financial Condition and Results of Operations (form 10-Q) - marketscreener.com - May 9th, 2020
- BrainStorm Leases a New Cleanroom Facility at The Tel Aviv Sourasky Medical Center to Manufacture NurOwn for The European Union - BioSpace - May 7th, 2020
- Stem Cells Market 2020 Size, Global Trends, Comprehensive Research Study, Development Status, Opportunities, Future Plans, Competitive Landscape and... - May 7th, 2020
- Chinas scientists accused of playing God by creating monstrous cloned apes and primates with human organs - The Sun - May 7th, 2020
- Roeland Nusse receives Canada's Gairdner International Award | The Dish - Stanford University News - May 7th, 2020
- Broad Foundation brings together stem cell scientists, engineers and physicians at University of Southern - Mirage News - May 7th, 2020
- Schizophrenia drug points to improved brain cancer radiation therapy - New Atlas - May 7th, 2020
- Scientists finally explained one of the strangest coronavirus symptoms - BGR - May 5th, 2020
- What Do New Neurons in the Brains of Adults Actually Do? - The Scientist - May 5th, 2020
- Therapy Harnesses Immune System to Slow Progression of DIPG Brain Tumors - University of Michigan Health System News - May 5th, 2020
- Acute Myeloid Leukemia Therapeutics Market Latest Innovations, Drivers and Industry Key Events During Forecast 2017 2025 - Jewish Life News - May 5th, 2020
- Stemline Slated for Acquisition by Menarini in Deal Worth Up to $677M - Xconomy - May 4th, 2020
- Teva and Celltrion Healthcare Announce the Launch of TRUXIMA (rituximab-abbs) Injection for Rheumatoid Arthritis, the Only Biosimilar to Rituxan... - May 4th, 2020
- Genmab Announces U.S. FDA Approval of Subcutaneous Formulation of Daratumumab, DARZALEX FASPRO (daratumumab and hyaluronidase-fihj), for the Treatment... - May 4th, 2020
- Stem cell therapy shows 83% survival of Coronavirus patients on ventilators - International Business Times, Singapore Edition - April 26th, 2020
- There's no treatment for COVID-19, but Virginia researchers are ramping up clinical trials to try to find one - Richmond.com - April 26th, 2020
- Newest American Academy of Arts and Sciences members | Stanford News - Stanford University News - April 26th, 2020
- 'I Will Not Kill Children to Live' - Church Militant - April 24th, 2020
- Morning Update: Canadas data gaps are hurting our ability to fight the pandemic - The Globe and Mail - April 24th, 2020
- Adult Stem Cell - an overview | ScienceDirect Topics - April 12th, 2020
- Coronavirus updates: Masks required for take out; N.J. hospitalizations to peak within 3 weeks; Stimulus paym - NJ.com - April 12th, 2020
- 4 ways to promote neurogenesis in your brain - Big Think - April 9th, 2020
- Funding roundup: At-home medical exams and a Parkinson's treatment - MedCity News - April 9th, 2020
- Moderna: A $12 Billion Brand Built On Hope And mRNA - Seeking Alpha - April 9th, 2020
- BrainStorm Awarded $1.5 Million Non-Dilutive Grant for 2020 by the Israel Innovation Authority - Yahoo Finance - April 3rd, 2020
- Post-Remission Therapy For AML: Allogeneic Stem-Cell Transplant - SurvivorNet - April 3rd, 2020
- Intermittent fasting might boost the creation of new neurons in a key brain structure - PsyPost - April 3rd, 2020
- 4 relationship problems that can be linked back to early childhood - Big Think - March 28th, 2020
- Scientists Have 'Reset' The Cellular Age Of Cells Taken From A 114-Year-Old Woman - IFLScience - March 26th, 2020
- The Answer to the Coronavirus Is More Abortion? - Townhall - March 24th, 2020
- Mesoblast limited (NASDAQ:MESO) Given Consensus Rating of Buy by Brokerages - Redmond Register - March 21st, 2020
- Stem Cell And Regenerative Therapy Market 2019-2024 Chain Analysis, Upstream Raw Materials Sourcing and Downstream Buyers - Feed Road - March 15th, 2020
- Scientists Create Human 'Body-On-A-Chip' Featuring Tiny Replica Organs In The Lab - IFLScience - March 14th, 2020
- Adult Stem Cells - March 12th, 2020
- Australia's Mesoblast plans to evaluate its stem cell therapy in patients infected with COVID-19 - BioWorld Online - March 12th, 2020
- How to build a body from scratch, Altered Carbon-style - SYFY WIRE - March 12th, 2020
- Astronauts growing new organs on International Space Station - The Independent - March 12th, 2020
- The Inside Scoop on Northwest Biotherapeutics, Inc (OTCMKTS: NWBO) - MicroCap Daily - March 9th, 2020
- Adult Stem Cells: Market 2020 New Innovative Solutions to Boost Global Growth with New Technology, Key Business Strategies, Trend and Forecasts 2024 -... - March 6th, 2020
- Review Finds The Effects Of Obesity On The Body Mirror Those Of Aging - IFLScience - February 29th, 2020
- Stem Cells Market is expected to reach US$270.5 billion by 2025, TMR - BioSpace - February 24th, 2020
- Olive Oil Consumption Could Lead to a 'Younger Brain' in the Elderly, Researchers Say - Olive Oil Times - February 24th, 2020
- New sickle cell disease treatments are helping people live longer and giving them a higher quality of life - PhillyVoice.com - February 24th, 2020
- Proteostasis Therapeutics and CF Europe Announce Completion of Patient Enrollment for CHOICES, the First-Ever Personalized Medicine-Based Study in... - February 24th, 2020
- Transplant for Szary Syndrome is Patient's First Step in Returning to the Dance Floor - Dana-Farber Cancer Institute - February 22nd, 2020
- Eternal youth and good health from stem cells soon within reach? - Innovation Origins - February 22nd, 2020
- How do body parts grow to their right sizes? - The Week Magazine - February 22nd, 2020
- 8-year-old bone marrow recipient and donor celebrate in emotional reunion - WFAA.com - February 16th, 2020
- Singapore researchers discover Human Stem Cells and Cancer Origins in Stomach - BSA bureau - February 14th, 2020
- Stem Cell And Regenerative Therapy Market Sales Volume, Status, Growth, Opportunities and World - Instant Tech News - February 14th, 2020
- Astrocytes could be harnessed to protect motor neurons in MND - Drug Target Review - February 11th, 2020
- BrainStorm Cell Therapeutics and FDA Agree to Potential NurOwn Regulatory Pathway for Approval in ALS - Yahoo Finance - February 11th, 2020
- Mexico City Medical Congress to Showcase the Global Stem Cells Group's Latest Innovations - PRUnderground - February 11th, 2020
- Bone Therapeutics to present preclinical data on the osteogenic properties of ALLOB in bone repair at the Annual Meeting of the Orthopaedic Research... - February 11th, 2020
- Stopping Smoking Allows Healthy Lung Cells to Proliferate - Medscape - February 6th, 2020
- Biological robots, that is a thing now - 702 - February 6th, 2020
- How the next trip to the moon will get us ready for Mars - Deseret News - February 6th, 2020
- Knocking Down Levels Of These Proteins Could Reverse Type 2 Diabetes - International Business Times - February 6th, 2020
- Efficacy and Safety of Sonidegib in Adult Patients with Nevoid Basal C | CCID - Dove Medical Press - February 2nd, 2020
- People who develop Parkinson's before 50 may have been born with damaged brain cells, says study - MEAWW - February 2nd, 2020
- Single-cell analysis reveals different age-related somatic mutation profiles between stem and differentiated cells in human liver - Science Advances - January 31st, 2020