Victoria Gray, a 34-year-old mother of four in Forest, Miss., had been going to the hospital seven times a year for transfusions to help with the severe pain brought on by her sickle cell disease. In July 2019, she volunteered for a radical new technology known as gene editing. She has been free of the pain and suffering since.
I chose to participate in this trial because of hopehope that it would change my life, Gray tells Barrons. And it has already in so many ways.
Her successful treatment gives hope to the 100,000 other Americans who suffer from sickle cell. It also illuminates the enormous potential for the companies that are pioneering genetic medicine to cure diseases with a one-time treatment.
Sickle cell is among their first targets. The companies include the sponsors of Victoria Grays clinical trial Crispr Therapeutics (ticker: CRSP) and Vertex Pharmaceuticals (VRTX)as well as biotechs like bluebird bio (BLUE), whose gene therapy for sickle cell is further along in testing and could be introduced by 2022.
For these companies, genetic therapies for sickle cell could fetch annual revenue of several billion dollars apiece. A recent Bank of America Securities report predicts that new treatments for sickle cell will surpass $6 billion in sales by 2028. That is meaningful for a company of any size, but particularly so for these biotechs. Crispr doesnt yet have sales. Bluebirds revenue last year was $45 million, and Vertexs, $4 billion.
More important, the sickle cell therapies will demonstrate how such genetic technology could open the door to curing dozens of other diseases.
Investors seem persuaded. They have lifted Crispr stock threefold since March to a recent high of $97, which values the development-stage company above $6 billion. Hitting a record high of $306, Vertexs value has topped $75 billion, while bluebirdwhose investors have waited nearly a decade for their paydaytrades at a more modest market cap of $4.2 billion. Biotech valuations may be hard to rationalize these days, but that reflects the radical changes that new technologies are bringing to the health-care business. One need look only at this years fourfold rise of the messenger RNA vaccine leader Moderna (MRNA).
The focus on sickle cell is a turnaround for the pharmaceutical industry, which had long ignored the inherited disorder. Sickle cell mainly afflicts Black Americans and residents of poor African nations. It is the most commonly diagnosed genetic disorder among newborn Americans. Yet it has not had as much funding as some less-common inherited conditions. Cystic fibrosis, for example, affects one-third as many Americans, but researchers at Duke University have shown that it has historically received more than seven times the federal and foundation research funding per patient.
This year, two new sickle cell drugs came on the market. And sometime next year, bluebird will ask the U.S. Food and Drug Administration to approve its sickle cell gene therapy. Crispr and Vertex hope that they will not be not far behind.
The starting prices of the new sickle cell treatments are expected to range from $100,000 to over $1 million. It will be a challenge to make them accessible to the millions of people in poor countries who have sickle cell.
The disease is caused by a single variation in a gene for hemoglobin, the protein that carries oxygen in our red blood cells. The genetic trait is prevalent among those whose descent traces to sub-Saharan Africa, because a single copy of the sickle cell gene protects you from developing malaria. Inherit a copy from each parent, however, and you become one of 300,000 babies born in the world each year with sickle cell disease. It causes hemoglobin molecules to form long chains that warp red blood cells into sickle shapes that get stuck in blood vessels and block the flow to vital organs.
The result is terrible pain, organ damage, infections, andwhen left untreateddeath before age 5, on average. In the U.S., where the disease occurs in one of every 365 Black babies, available treatments still leave many with a life of pain, disability, and death before age 50.
The first sickle cell treatment approved by the U.S. Food and Drug Administration was hydroxyurea, in 1998. For the half of sickle cell patients with moderate disease, treatment with hydroxyurea, antibiotics, and transfusions can allow productive lives. Hydroxyurea is off-patent and costs less than a dollar a day. But even that price is beyond reach of those who live in resource-poor countries, says Russell Ware, a pediatric hematology professor at the University of Cincinnati College of Medicine. Ware is working with medical colleagues in Uganda to get more children there on hydroxyurea.
Data as of 7/22/20
Bloomberg; company filings
The beauty is that its off-patent, says Ware, but its also a curse, because no one can make money off it.
Novartis (NVS) is supporting hydroxyurea availability in collaboration with the government of Ghana. The Swiss drug giant is also planning clinical trials in Ghana and Kenya for Adakveo, a monoclonal antibody approved by the FDA last November as one of the first novel treatments in decades for sickle cell disease. Adakveo dampens the inflammatory process that makes sickle cells clog blood vessels in cases that send some 50,000 Americans to the emergency room every year.
The intravenous drugs initial sales in the years first half were $36 million, but analysts hope that by the middle of this decade, Adakveos annual sales could reach $1 billion to $2 billion in the U.S. and Europe.
Just days after approving the Novartis drug, the FDA approved another sickle cell drug called Oxbryta, from Global Blood Therapeutics (GBT). Oxbryta is a pill that prevents defective hemoglobin from forming chains within red blood cells. The product is GBTs first, and it produced $14 million in sales for the March quarter, with a loss of $73 million.
But analysts like Yatin Suneja of Guggenheim Securities say that Oxbryta can hit sales of $1.7 billion in a few years, yielding some $13 a share in earnings for GBT. That makes Suneja think that GBT stock can rise from its current level of $72 to $115.
Successful sickle cell treatments could lift a number of biotech companies.
GBT CEO Ted Love says that Oxbrytas benign safety profile gives the company confidence that it will win approval to market the product for children, and in higher doses for adults. If other sickle cell treatments in the companys pipeline pan out, he imagines that sickle cell might one day become as well managed a disease as HIV.
Love is aware of the potentially curative gene therapies being tested by others, but he thinks that patients with milder cases of sickle cell might say, Just give me a pill.
For several decades, it has been possible to cure sickle cell with a bone-marrow transplant from a related donor. But the scarcity of matched donors and the risk of serious immune reactions have limited the number of such procedures to about 1,000. Recent breakthroughs in genetic technology promise to overcome those limitations by extracting a patients own cells, manipulating the cells genetic code, and then replacing the patients marrow with the amended cells.
The Cambridge, Mass.based bluebird bio is already in Phase 3 clinical trials of its beti-cel gene therapy for another inherited disorder of red blood cells called beta-thalassemia. Less common than sickle cell, thalassemia leaves patients with so few red blood cells that they can need more than a dozen transfusions a year. At a recent online gathering of hematologists, bluebird said that 60 children and adults with thalassemia had gone through its beti-cel procedure. About 90% had gone a year without needing a single transfusion.
Receive a regular newsletter highlighting our top stories, along with updates and special offers from Barron's.
With a similar treatment for sickle cell, which bluebird calls LentiGlobin, more than two dozen patients have been infused with their own modified cells. Among the 14 patients who were six months past their treatment, there has been a 99.5% decrease in the blood vessel jam-ups that the patients previously suffered.
That is fundamentally transformative, says bluebird CEO Nick Leschly, and far exceeds any and all expectations weve ever had, any of our investigators have ever had, or the patients that have been treated.
These potentially curative cell therapies are complex procedures that are expected to be priced at about $1 million a patient. The thalassemia treatment is already approved in Europe. After the patients in bluebirds U.S. trials for thalassemia and sickle cell have been followed up for 18 months, the company will seek FDA approvalhopefully next year.
RBC Capital Markets believes that the companys sickle cell treatment could reach sales of $2 billion a year and help lift bluebird stock from its recent price of $66 to $100.
It took bluebird a decade to get to this point, and its shares have sunk as low as $17 and soared as high as $236, as investors reacted to the companys dramatic successes against refractory cancers. With Buy recommendations all along Wall Street, bluebird will get the capital it needs to cross the finish line.
Hard on the heels of bluebird are companies that believe they have better genetic treatments. One of them is Crispr Therapeutics. The company takes its name from CRISPR, shorthand for a Nobel Prizewinning technology that homes in on a targeted stretch of DNA and snips the double-stranded molecular code with a kind of chemical scissors.
The way I describe it to my patients, says patient Grays doctor Haydar Frangoul, at the Sarah Cannon Research Institute in Nashville, is that you have a book with 500 pages of thousands of words, and we are finding one word and correcting it.
Crispr Therapeutics CEO Sam Kulkarni says that CRISPR technology should provide more durable and uniform results than earlier generation treatments like bluebirds. When Crispr reported Grays healthy progress last month, it said that a second patient with sickle cell has also been treated, as well as five patients with thalassemia. Kulkarni hopes to reach the market with his treatments not too far behind bluebird.
This years surge in Crispr Therapeutics stock allowed it to raise about $450 million in a June stock offering. Jefferies analyst Maury Raycroft has estimated that a successful sickle cell treatment could contribute a third of the $5 billion in annual revenue he projects for Crispr by 2030, with earnings above $30 a share. The stock has blasted through his last price target of $82.
Behind Crispr are still other gene-editing companies working on treatments for thalassemia and sickle cell, including Sangamo Therapeutics (SGMO), Editas Medicine (EDIT), and Intellia Therapeutics (NTLA).
One of this years most successful initial public offerings was the February debut of Beam Therapeutics (BEAM), which is in preclinical testing of sickle and thalassemia treatments that would use a next-generation editing technology that CEO John Evans believes will be even more effective than CRISPR.
If these other companies sickle cell treatments pan out, they may be scrapping for market share after bluebird and Crispr have established products. Still, as the pharmaceutical giants shop for gene-editing know-how, there may be buyouts.
Sickle cell has been a long-neglected illness, but many companies are now competing with treatments that each hopes will be best-in-class. This should be a dogfight, says bluebird CEO Leschly, because thats in the interest of patients.
Write to Bill Alpert at email@example.com
- Reducing barriers to mainstream gene therapy - BioPharma-Reporter.com - September 4th, 2020
- Mapping Genetic Diversity of Lung Tumors Over Time May Lead to More Effective Therapies - UCSF News Services - September 4th, 2020
- Multi-site study to evaluate the role of testing guidelines in ensuring access to genetic information for men with prostate cancer - PRNewswire - September 4th, 2020
- Global Prime Editing Market to Witness Heightened Growth During the Period 2020 2030 - The Daily Chronicle - September 4th, 2020
- Liquid biopsies to disrupt the oncology testing market - Medical Device Network - September 4th, 2020
- Global RNA-interference (RNAi) Market Growth, Trends and Forecasts to 2025: Focus on Key Players Alnylam Pharmaceuticals, Arrowhead, Quark... - September 4th, 2020
- Yale researchers find a cause and possible treatment for Fragile X - Yale News - September 4th, 2020
- 'Coming into their own': FDA approval of liquid biopsy tests puts early, less invasive cancer detection in broader reach - USA TODAY - September 4th, 2020
- Fusion Genes Associated With More Aggressive Papillary Thyroid Cancer in Pediatric Patients - Targeted Oncology - September 4th, 2020
- Existing Class of Drugs May Improve Neurological Function in Patients with Rare, Aggressive Genetic Disorder - Newswise - September 4th, 2020
- Genomic analysis reveals insights on virulent, emerging foodborne pathogen - UB Now: News and views for UB faculty and staff - University at Buffalo... - September 4th, 2020
- Hyperthyroidism is associated with breast cancer risk and mammographic and genetic risk predictors - 2 Minute Medicine - September 4th, 2020
- Health history platform launches to trace genetic conditions | Digital Healthcare - Healthcare Global - Healthcare News, Magazine and Website - September 4th, 2020
- New HIV Gene Therapy, CAR-T Treatments Could be on the Horizon for Patients - BioSpace - September 4th, 2020
- Cell Suicide Gene Further Linked to Immunotherapy Response - Technology Networks - September 2nd, 2020
- Genetic mutations may be linked to infertility, early menopause - Washington University School of Medicine in St. Louis - September 2nd, 2020
- How to use precision medicine to personalise COVID-19 treatment according to the patient's genes - Down To Earth Magazine - September 2nd, 2020
- UCT professors research offers hope of treatment for sickle cell anaemia - Daily Maverick - September 2nd, 2020
- Association of recent stressful life events with mental and physical health in the context of genomic and exposomic liability for schizophrenia - 2... - September 2nd, 2020
- Finding order in the chaos of cancer mutations - Drug Target Review - September 2nd, 2020
- Mustang Bio Announces Orphan Drug Designation for MB-107 for the Treatment of X-linked Severe Combined Immunodeficiency in Newly Diagnosed Infants -... - September 2nd, 2020
- Novavax Announces Publication of Phase 1 Data for COVID-19 Vaccine Candidate in The New England Journal of Medicine - GlobeNewswire - September 2nd, 2020
- Department of Genetic Medicine | Johns Hopkins Medicine - August 10th, 2020
- Genetic Medicine | Internal Medicine | Michigan Medicine ... - August 10th, 2020
- Genetic Medicine | Department of Medicine - August 10th, 2020
- Genomics and Medicine - Genome.gov - August 10th, 2020
- New Approach to Treating Osteoarthritis Advances | NYU Langone News - NYU Langone Health - August 10th, 2020
- Stoke Therapeutics Reports Second Quarter Financial Results and Provides Business Updates - Business Wire - August 10th, 2020
- Here's Why Shares of Editas Medicine and Beam Therapeutics Are Soaring Today - Motley Fool - August 10th, 2020
- Grant will fund study into COVID outcome disparities in NYC - Cornell Chronicle - August 10th, 2020
- A versatile genetic control system in mammalian cells and mice responsive to clinically licensed sodium ferulate - Science Advances - August 10th, 2020
- Spark Therapeutics Deepens Drug Development Expertise in Hematology and Rare Disease with Appointment of Gallia G. Levy, MD, Ph.D., as Chief Medical... - August 10th, 2020
- Chromosomal Rearrangements Associated with Chemotherapeutic Drug Resistance | McDonnell Boehnen Hulbert & Berghoff LLP - JD Supra - August 10th, 2020
- Jae Jung, Ph.D., Appointed as Chair of Cleveland Clinic Lerner Research Institute's Department of Cancer Biology - Health Essentials from Cleveland... - August 10th, 2020
- The UK and TCELS to jointly support COVID-19 research in Thailand - GOV.UK - August 10th, 2020
- Akouos Announces Expansion of Executive Team and Board of Directors - BioSpace - August 10th, 2020
- Medical and neurobehavioural phenotypes in male and female carriers of Xp22.31 duplications in the UK Biobank. - Physician's Weekly - August 10th, 2020
- Coronavirus vaccine breakthrough: New generation cure that stops virus developed - Express - August 10th, 2020
- Global Cell and Gene Therapy Market, Forecast to 2025 by Product, Disease, End-user and Region - COVID-19 Updated - PRNewswire - August 10th, 2020
- Not Everyone Needs 8 Hours of Sleep, New Research Reveals | Time - TIME - August 10th, 2020
- Lindsey Criswell Named Director of National Institute of Arthritis and Musculoskeletal and Skin Diseases - UCSF News Services - August 10th, 2020
- Pinpointing The Cells That Keep The Bodys Master Circadian Clock Ticking - Newswise - August 10th, 2020
- Kazia Therapeutics hits A$1 on grant of Rare Pediatric Disease Designation to paxalisib for DIPG - Proactive Investors USA & Canada - August 10th, 2020
- Treatment Considerations for Prostate Cancer Progressing After Combination Therapy for mCSPC - UroToday - August 10th, 2020
- Edited Transcript of PSNL.OQ earnings conference call or presentation 6-Aug-20 9:00pm GMT - Yahoo Finance - August 10th, 2020
- Ovid and Angelini partner on treating Angelman syndrome in Europe - Pharmaceutical Technology - August 10th, 2020
- Doctoral Student/Research Assistant in Mitochondrial Biology and Signalling job with UNIVERSITY OF HELSINKI | 218596 - Times Higher Education (THE) - August 10th, 2020
- Simpler COVID-19 test could provide results in hours from saliva - University of Wisconsin-Madison - August 10th, 2020
- This company has a better version of a simpler, faster Covid-19 test - STAT - August 7th, 2020
- Mental Notes: Music Cognition Lab is dedicated to the scientific study of how music affects the brain and behavior - Vanderbilt University News - August 6th, 2020
- Nasha Fitter Elected to Board of Directors of the ACMG Foundation for Genetic and Genomic Medicine - PRNewswire - August 5th, 2020
- HDAC6 Can Control Tumor Growth and Halt Metastasis in Triple-Negative Breast Cancer - Newswise - August 5th, 2020
- Will programming a cell ever be as easy as programming an app? - SynBioBeta - August 5th, 2020
- Penn Researchers Identify New Genetic Cause of a Form of Inherited Neuropathy - Newswise - August 5th, 2020
- Genetic Variant in Persons of African Descent Linked with Stroke: Analysis - DocWire News - August 5th, 2020
- Invitae Reports $46.2 Million in Revenue Driven by More Than 120000 Samples Accessioned in the Second Quarter of 2020 - Monterey County Weekly - August 5th, 2020
- Noel R. Rose, widely regarded as the father of autoimmune disease research, dies at 92 - The Hub at Johns Hopkins - August 5th, 2020
- Atsena Therapeutics acquires exclusive rights to Gene Therapy for GUCY2D-associated Leber Congenital Amaurosis - GlobeNewswire - August 5th, 2020
- Seragon Announces GenomeScore, the First AI Platform to Measure Rate of Aging and Physiological Changes - PRNewswire - August 5th, 2020
- Vaccine 'durability': COVID-19 immunizations coming soon but will they last? - Genetic Literacy Project - August 5th, 2020
- Aerpio Pharmaceuticals, Inc. Announces a Second Clinical Trial with Funding from MTEC to Evaluate Razuprotafib for the Prevention and Treatment of... - August 5th, 2020
- Stoke Therapeutics to Present at Upcoming Investor Conferences in August - Business Wire - August 4th, 2020
- The global cell and gene therapy market by revenue is expected to grow at a CAGR of over 30.90% during the period 20192025 - GlobeNewswire - August 4th, 2020
- Cochlear implant uses LEDs to tackle hearing loss - Optics.org - August 4th, 2020
- Rozlytrek, Roche's first tumour-agnostic therapy, approved in Europe for people with NTRK fusion-positive solid tumours and for people with... - August 4th, 2020
- Alnylam Pharmaceuticals : Submits CTA Application for ALN-HSD, an Investigational RNAi Therapeutic for the Treatment of Nonalcoholic Steatohepatitis -... - August 4th, 2020
- 'The younger the child, the likelier to find causative gene of infant epilepsy' - Korea Biomedical Review - Korea Biomedical Review - August 3rd, 2020
- Known genes associated with male infertility doubled - BioNews - August 3rd, 2020
- Alnylam Submits CTA Application for ALN-HSD, an Investigational RNAi Therapeutic for the Treatment of Nonalcoholic Steatohepatitis (NASH) - Business... - August 3rd, 2020
- Cancer drug is first therapy to emerge from 23andMe-GSK deal - STAT - STAT - August 3rd, 2020
- Dr. Rana on the Rationale for Video Genetic Counseling in Prostate Cancer - OncLive - August 3rd, 2020
- Metastatic Lung Cancer Study Finds That Bionano's Saphyr Outperforms NGS for the Detection of Structural Variants - GlobeNewswire - August 3rd, 2020
- Health Media in the COVID-19 Era: A mid-wave report - Features - MM&M - Medical Marketing and Media - August 3rd, 2020
- Cyberpunk 2077 shows off the ruined dreams district of Pacifica in new concept art - Critical Hit - August 2nd, 2020
- An unsupported American conspiracy theory found a foothold in Europe. New research shows how - NewsDio - August 2nd, 2020
- Study Suggests New Approach to Improve Radiation Therapy Resistance in Glioblastoma - Michigan Medicine - August 1st, 2020
- Atsena Therapeutics acquires exclusive rights to Gene Therapy for GUCY2D-associated Leber Congenital Amaurosis - BioSpace - August 1st, 2020
- Our Genes May Explain Severity of COVID-19 and Other Infections - Quanta Magazine - August 1st, 2020
- Omega Therapeutics Lands $85M to Tap Into Control Room of Biology - Xconomy - August 1st, 2020
- EarlyBird Study: Early Detection of Adult-Onset Type 2 Diabetes in Youth - Diabetes In Control - August 1st, 2020