Editor's note: BioPharma Dive, as part of our gene therapy coverage, is taking a closer look at inherited diseases for which researchers are developing genetic medicines. We aim to give a brief overview of the pipeline and lay out what could come next for such drugs. This, on sickle cell disease, is our latest.
Sickle cell disease is one of the world's most common inherited blood disorders, though that isn't reflected in the number of treatments for it. Three new drugs hit the market between 2017 and 2019. But before those additions, nearly two decades had passed since the Food and Drug Administration last approved a sickle cell medicine.
Now, a handful of companies are looking to not just treat the disease, but potentially cure it. Their goal, broadly, is to fix the mutations that cause sickle cell through the use of cutting-edge gene editing technologies. One of these treatments has already advanced to the final stage of human testing, and is expected to be submitted for approval late next year or early in 2023.
A one-time, possibly curative treatment would be momentous, as the median life expectancy for someone living with sickle cell is estimated to be between 45 to 55 years in the U.S. The disease also causes strokes, organ damage and episodes of severe pain known as vaso-occlusive crises. Genetic medicines developed by Bluebird bio and by CRISPR Therapeutics and Vertex Pharmaceuticals have shown promising signs that they can mostly eliminate vaso-occlusive crises, although further testing is needed to better understand if they have limitations or if their effects might wear off over time.
Such treatments raise tough questions, though. Gene-based treatments are very expensive and fairly difficult to make, which presents a major problem in sickle cell given that many people with the disease live in lower-income countries. Drug developers like Novartis say they're tailoring their work to address some of these issues, but it's unclear how well they'll be able to remedy long-standing problems of access and equity.
Sickle cell is caused by mutations in the gene that creates hemoglobin, the protein on red blood cells responsible for carrying oxygen.
Patients therefore experience the disease differently depending on their genetic make-up. Those with two copies of the mutated gene have more serious symptoms, like anemia, which happens because sickled red blood cells die much sooner than their healthy counterparts.
Sickled cells are also hard, sticky and misshapen, so they pose the threat of clumping together and causing a stroke.
In more severe cases, the symptoms require patients to get blood transfusions. There are also a few medications available specifically for complications of the disease, in particular the painful episodes that happen when sickled cells clog a blood vessel. The FDA approved a drug called hydroxyurea in the late 1990s for adults experiencing these vaso-occlusive crises. Then it approved another, an oral powder, in 2017.
In 2019, the FDA cleared two more medicines for market: Novartis' Adakveo, which helps reduce the frequency of vaso-occlusive crises, and Global Blood Therapeutics' Oxbryta, which is meant to inhibit red blood cells from sickling and breaking down. Novartis and Global Blood set the monthly list prices for their drugs between $7,000 and $10,400.
Additionally, a cure for sickle cell exists in the form of bone marrow transplants, though the treatments can cause life-threatening side effects and even death.
As with other diseases, genetic medicines for sickle cell are being positioned as long-lasting and, potentially, curative treatments.
If the therapies now showing promise continue to prove effective over time, they could eliminate the long-term symptoms of sickle cell, allowing patients to go without blood transfusions. Lessening or removing the need for blood transfusions would both lower the cost of care as well as avoid the related buildup of iron in the blood, which can require separate treatment.
Gene-based treatments could also prevent vaso-occlusive crises a main reason for hospitalization among sickle cell patients, who sometimes need strong painkillers like opioids.
Some clinical studies of sickle cell gene therapies are enrolling children. However, should any therapy come to market, older children or adults would likely be the first recipients, given the risks and uncertainties.
A handful of companies have ushered genetic medicines for sickle cell into clinical trials, with the majority still in earlier stages. The farthest along is Bluebird's LentiGlobin, which is designed to deliver an engineered version of the gene that codes for hemoglobin.
SOURCE: Companies, clinicaltrials.gov
To make LentiGlobin, Bluebird takes a patient's stem cells, uses special viruses to outfit them with the corrected gene and then reinfuses them.
This is different from the gene-editing approach favored by several other main developers. At least two sets of partners CRISPR and Vertex, and Novartis and Intellia Therapeutics are using the Nobel Prize-winning CRISPR-cas9 technology to get stem cells to produce high levels of what's known as fetal hemoglobin. Fetal hemoglobin is a form of the vital protein, but it stops being produced roughly six months after a person is born. Gene editing, in theory, keeps the switch for this protein on, helping remedy the main problems associated with sickle cell.
Genetic medicines have already shown promise treating sickle cell. A small study of Bluebird's found that, after treatment, hemoglobin levels were close to what's considered normal, and almost no patients experienced vaso-occlusive crises or acute chest syndrome, another symptom of the disease.
CRISPR and Vertex gave a similarly positive update on their program last month. The companies' said that the small group of sickle cell patients given their therapy, named CTX001, had yet to experience vaso-occlusive crises following treatment. Data also suggest their therapy can have a long-lasting effect.
The breakthroughs didn't come without setbacks, however. Bluebird's LentiGlobin program has faced multiple delays tied to manufacturing and safety concerns. In February, the company halted two of its sickle cell studies after one participant developed leukemia and another appeared to have a disease of the bone marrow. Bluebird has since conducted an investigation and determined its therapy was "very unlikely" to be related to the cancer case.
In April, Bluebird said the bone marrow diagnosis had been revised to a condition known as transfusion-dependent anemia.
Bluebird was allowed to resume its sickle cell studies in June. Prior to the study halt, the company had said it planned to ask for approval in late 2022, although that may now be delayed.
Sticking to that timeline would put Bluebird well ahead of rival therapies, according to an analysis by the investment bank Raymond James. The next closest is CRISPR and Vertex's treatment, which Raymond James analysts think could be submitted for approval in two to three years. Testing, after a slower start, is now moving quickly, however.
Behind that, genetic medicines from Aruvant Sciences and partners Sanofi and Sangamo Therapeutics are on track to be filed in three to five years, according to Raymond James.
In the meantime, there are many uncertainties to contend with. Researchers are still trying to understand whether genetic medicine will work for all sickle cell patients, or whether it'll live up to its potential as a lifelong fix for the disease.
Even if these treatments do reach the market, they'll likely still face challenges. For example, therapies currently in development use toxic conditioning regimens to prepare patients' bodies for cell reinfusion, and that may restrict who's able or willing to receive them.
In a recent note, analysts at Stifel wrote that they see the toxic regimens as "limiting the commercial opportunity" for the kinds of treatments being developed by Bluebird, Vertex and CRISPR. "We of course view these events in the context of profound efficacy," the analysts wrote, "but even so, we don't expect the risk/benefit of these agents to resonate with younger, more mild patients."
Read the original:
Gene therapy for sickle cell disease: progress and competition - BioPharma Dive
- SUM Hospital conducts Odishas first stem cell transplantation - The Times of India - April 24th, 2024
- Cancer treatment: What is stem cell therapy, and how does it work? - Moneycontrol - April 24th, 2024
- The murky, unregulated world of anti-ageing stem cell therapy - The Telegraph - April 24th, 2024
- Drug Prototype Promising in Treatment of Pulmonary Disease - Medscape - April 20th, 2024
- Man Paralyzed In Surfing Accident Regains Ability to Walk After Stem Cell Treatment - The Inertia - April 20th, 2024
- Medical breakthrough: 8-year-old boy first in New York to receive FDA-approved gene therapy for rare inherited blood disorder - WABC-TV - April 20th, 2024
- Stem Cell Treatment Helped A Man Who Was Paralyzed From The Neck Down To Stand On His Own - Bored Panda - April 20th, 2024
- UM, CUHK jointly hold symposium on stem cells and regenerative medicine - gcs.gov.mo - April 20th, 2024
- Paralysed patient now able to walk as stem cell therapy shows promising results - WION - April 15th, 2024
- Andrew Steele Sees Aging as the Root of Disease - Worth - Worth Magazine - April 15th, 2024
- The astonishing effect of stem cell implants - as groundbreaking treatment 'transforms' life for those with brain damage ... - Daily Mail - April 15th, 2024
- Consumer Alert on Regenerative Medicine Products Including Stem Cells - FDA.gov - April 13th, 2024
- This Startup Wants To Be OpenAI Of Stem Cell Therapy, Targets $250B Market - Forbes - April 13th, 2024
- Brain-cell transplants are the newest experimental epilepsy treatment - MIT Technology Review - April 3rd, 2024
- Global Regenerative Medicine Market to Touch Valuation of USD 472.95 Billion by 2032, at 25.86% CAGR: Astute ... - Yahoo Finance - April 1st, 2024
- Explosive Growth Projected for Stem Cell Market, Expected to Surpass $37 Billion by 2030 As Revealed In New... - WhaTech - April 1st, 2024
- Integrating New Therapies With Autologous Stem Cell Transplant in Myeloma - Targeted Oncology - April 1st, 2024
- New tool provides researchers with improved understanding of stem cell aging in the brain - Medical Xpress - March 30th, 2024
- The ISSCR announces 2024 election results - EurekAlert - March 28th, 2024
- Exosomes and Stem Cells Are the Future of Anti-Aging - NewBeauty Magazine - March 28th, 2024
- Charles River Extends Gene Therapy Alliance with NUS Medicine - Contract Pharma - March 22nd, 2024
- Exciting opportunities in stem cell technology and regenerative biology in Indian healthcare industry - Express Healthcare - March 22nd, 2024
- Charles River Announces Extension of Gene Therapy Manufacturing Alliance with NUS Yong Loo Lin School of Medicine - Yahoo Finance - March 22nd, 2024
- Opinion: The revolutionary sickle cell therapies - MSN - March 22nd, 2024
- 10 Years of Kansas Regenerative Medicine Center - KSAL - March 22nd, 2024
- BioCardia and StemCardia Announce Biotherapeutic Delivery Partnership - Diagnostic and Interventional Cardiology - March 17th, 2024
- Cynata Therapeutics' breakthrough in regenerative medicine - Finance News Network - March 17th, 2024
- New Positive Data Presented on Briquilimab Conditioning in Patients with Fanconi Anemia - GlobeNewswire - March 17th, 2024
- Novel 3D stem cell therapy to treat critical limb ischaemia - Drug Target Review - March 15th, 2024
- Breaking Boundaries: Pharmicell's Bold Vision for Healthcare Transformation and Monumental Growth - The Worldfolio - March 15th, 2024
- CuSTOM Organoid Research Evolving From Tool to Treatment - Research Horizons - Research Horizons - March 15th, 2024
- BioCardia and StemCardia Announce Partnership to Deliver Cell-Gene Therapy for Remuscularization of Heart - Cath Lab Digest - March 15th, 2024
- Calidi Biotherapeutics and City of Hope Announce Funding from the California Institute for Regenerative Medicine ... - Business Wire - March 13th, 2024
- Iron restriction keeps blood stem cells young, researchers find - Phys.org - March 13th, 2024
- Vitamin A could have a key role in both stem cell biology and wound healing: Study - Medical Dialogues - March 9th, 2024
- Trends in Stem Cell Transplantation Refusal for Myeloma Treatment - Targeted Oncology - March 7th, 2024
- Stem Cell Therapy Market (CAGR) of 31.1%, Future of Market Size Emerging Technologies and their Impact on ... - Taiwan News - March 7th, 2024
- This Swedish startup wants to reduce the cost, and controversy, around stem cell production - TechCrunch - March 6th, 2024
- Advancing stem cell therapy: The regulatory process to get to clinical trials - The Economic Times - March 6th, 2024
- Transitioning from traditional surgical methods to the innovative use of stem cells - pharmaphorum - March 6th, 2024
- 'Mini organs' are grown from human stem cells taken during the late stages of pregnancy for the first time - m - Daily Mail - March 6th, 2024
- Stem cell transplant cures man of HIV and leukemia, one of five to achieve full remission - Fox 28 - March 3rd, 2024
- Stem Cell Therapy Market to Boost USD 137.5 Billion by 2034 and Projected to grow at 32.10% CAGR with increasing ... - Yahoo Finance - March 1st, 2024
- Studies expand use of stem cell therapies - WPLG Local 10 - March 1st, 2024
- Innovative therapy targets and destroys leukemia stem cells - News-Medical.Net - February 27th, 2024
- Unlocking the Potential of Stem Cells: The Medical Revolution of the Century - EIN News - February 27th, 2024
- Pelage Pharmaceuticals Announces $16.75M Series A Financing led by GV to Revolutionize Regenerative Medicine ... - Yahoo Finance - February 27th, 2024
- Say Her Name - Henrietta Lacks, The Real Mother Of Stem - Her Campus - February 27th, 2024
- California Man Free of HIV And Cancer in Astonishing Medical Recovery - ScienceAlert - February 25th, 2024
- $93 million for research into improved health for children, young people and the aged, medical devices, mental health ... - Department of Health - February 25th, 2024
- Stem Cells in Regenerative Medicine - PMC - National Center for ... - February 24th, 2024
- The Promise and Reality of Stem Cell Therapy: What You Need to Know - Corporate Wellness Magazine - February 22nd, 2024
- Stem Cell Therapy: A Beacon of Hope for Patients with Untreatable Conditions - Corporate Wellness Magazine - February 22nd, 2024
- Leading Experts in Stem Cell Therapy: A Global Overview - Corporate Wellness Magazine - February 22nd, 2024
- Can Stem Cells Help Reverse the Effects of Aging? - Corporate Wellness Magazine - February 22nd, 2024
- Stem Cell Therapy for Cancer: Hope on the Horizon? - Corporate Wellness Magazine - February 22nd, 2024
- Stem Cells and Autism: A Closer Look at Innovative Treatments - Corporate Wellness Magazine - February 22nd, 2024
- Regrowth and Restoration: The Science Behind Stem Cell Therapy for Hair - Corporate Wellness Magazine - February 22nd, 2024
- Brain Recovery: The Role of Stem Cells in Stroke and Cerebral Palsy Treatments - Corporate Wellness Magazine - February 22nd, 2024
- Turning Back the Clock: The Science of Stem Cells in Anti-Aging - Corporate Wellness Magazine - February 22nd, 2024
- Insights into cellular therapies for cancer treatment - Drug Target Review - February 22nd, 2024
- The Role of Stem Cells in Rheumatoid Arthritis Recovery - Corporate Wellness Magazine - February 22nd, 2024
- Dr Ernesto Romeros vision transforms immunotherapy regenerative medicine into a global leader in stem cell treatment - Khaleej Times - February 22nd, 2024
- World-Renowned Doctors Leading the Way in Stem Cell Research and Treatment - Medical Tourism Magazine - February 20th, 2024
- Choosing the Best: A Guide to America's Premier Stem Cell Therapy Providers - Medical Tourism Magazine - February 20th, 2024
- Navigating Through the Possibilities of Stem Cell Treatment for Eye Disorders - Medical Tourism Magazine - February 20th, 2024
- Global Leaders in Stem Cell Therapy: Where Excellence Meets Innovation - Medical Tourism Magazine - February 20th, 2024
- Excellence in Stem Cell Treatment: How the US is Pioneering Global Healthcare Solutions - Medical Tourism Magazine - February 20th, 2024
- Clarifying Memory Loss Treatments: The Role of Stem Cells - Medical Tourism Magazine - February 20th, 2024
- Battling Inflammation: Stem Cell Therapy for Rheumatoid Arthritis - Medical Tourism Magazine - February 20th, 2024
- Digestive Health and Stem Cells: Treating Ulcerative Colitis and Crohn's Disease - Medical Tourism Magazine - February 20th, 2024
- Top Stem Cell Clinics in the USA: Pioneering Treatments for Chronic Conditions - Medical Tourism Magazine - February 20th, 2024
- Stem Cells and Autism: Understanding the Potential for Innovative Treatments - Medical Tourism Magazine - February 20th, 2024
- Stopping the awakening of sleeping Acute Myeloid Leukaemia stem cells to prevent disease relapse - University of Birmingham - February 20th, 2024
- City of Hope Achieves Ground Breaking Treatment for Blood Cancer and HIV - Medriva - February 18th, 2024
- Regenerative Medicine Market Size to Worth USD 95 Billion by 2032 - InvestorsObserver - February 18th, 2024
- North America Organoids Market Projected to Reach US$ 5.35 Billion by 2030, Riding on a CAGR of 21.5% - GlobeNewswire - February 18th, 2024
- Chinese team tests lung treatment that may be first to reverse COPD damage - South China Morning Post - February 15th, 2024
- Why leukemic stem cells not harmed by chemotherapy begin to grow and produce AML cells after treatment - Medical Xpress - February 15th, 2024
- Regenerative Medicine Market is Expected to Reach $49.0 Billion | MarketsandMarkets - Yahoo Finance - February 15th, 2024
Recent Comments