The coming weekend’s meeting of the American Society of Hematology brings news of breakthroughs in treating blood cancers. But the virtual ASH conference will also highlight advances for patients who suffer from nonmalignant blood disorders, like sickle cell disease and hemophilia. These diseases have become important test cases for the curative potential of genetic therapies.
Treatments that introduce healthy genes to the cells of people with the bleeding disorder hemophilia are looking good in clinical trials by
(ticker: QURE) and by the team of
(SGMO). Other approaches that edit a patient’s troublesome genes are also showing good results against artery-clogging sickle cell disease in trials by
(BLUE) and by a team of
(CRSP). And there will be promising data on less complex treatments with drugs from
Global Blood Therapeutics
The Dutch gene therapy firm uniQure generated excitement last month with the appearance of a research abstract ahead of ASH, with results from the first Phase 3 clinical trial of a gene therapy for hemophilia B. The 54 patients who got uniQure’s EtranaDez gene transfers saw their levels of a blood-clotting factor rise from an average of about 2% of normal, to 37%. That was enough to stop bleeding in 72% of them, and reduce it in the others. Nearly all were able to stop taking the replacement clotting factors that maintain most hemophilia patients.
Raymond James analyst Danielle Brill said in a note that she was impressed that uniQure’s treatment worked even in patients that had pre-existing antibodies to the defused virus used to deliver a healthy gene to patients’ cells. This evidence should differentiate EtranaDez from other gene therapies, she says. Brill rates uniQure a Strong Buy and thinks that the success of its investigational gene therapies for hemophilia and illnesses like Huntington’s disease will lift its stock from a recent $50 to $75.
Inadequate levels of a different clotting factor result from the other bleeding disorder known as hemophilia A.
(BMRN) is furthest along in trials of a gene transfer therapy. It sought approval from the U.S. Food and Drug Administration for its Roctavian treatment, after a Phase 3 clinical trial showed dramatic control of bleeding in treated patients.
But the FDA demurred in August, telling BioMarin that it should follow the patients for two years, after signs that clotting factor production dipped when steroid drugs were reduced. From $131, BioMarin stock fell by a third, and remains around $79. At a Piper Sandler conference Wednesday, BioMarin’s research head Henry Fuchs told investors that Europe’s drug regulators seem willing to consider one year’s worth of follow-up data, which will be ready in the second quarter of 2021. Hoping to impress the FDA, BioMarin will show it the one-year data, too.
In October, Pfizer started its Phase 3 trial of a hemophilia A therapy developed by Sangamo. Researchers will tell ASH attendees about the treatment’s earlier phase trial, where the highest dose of the gene therapy brought the patients’ clotting factor to normal levels and eliminated bleeding episodes.
The durability of gene transfer cures remains an open question that only time will answer. Gene-editing approaches change a person’s flawed genes, instead of just supplementing them, and promise a longer-lasting fix. The red blood cell defect caused by sickle cell is a good target for these treatments, and the farthest advanced in clinical trials is the LentiGlobin treatment from bluebird bio. Researchers will present the follow-up data for patients in bluebird’s Phase 1 and 2 study. More than a dozen have been followed for six months, and the treatment eliminated the dangerous and painful artery-clogging crises they’d previously suffered.
Vertex and Crispr Therapeutics are testing another kind of gene editing to treat sickle cell and a different red cell defect called beta-thalassemia. The first few patients in their clinical trials have been free of sickle cell crises, as well as the transfusions required by patients with untreated thalassemia.
Baird analysts said in a November 30 note that bluebird’s head start will allow it to submit an approval application in mid-2021 for a beta-thalassemia treatment and in 2022 for sickle cell. But the good performance of the treatments from Vertex and Crispr could win some market share when those reach the market, Baird opined. The companies will host an investor webcast on their ASH data on December 9.
Other gene editing firms are pursuing the same illnesses.
(NTLA) started a Phase 1 trial this year against sickle cell, with the backing of
(NVS). While Baird analyst Madhu Kumar thinks Crispr Therapeutics is fairly valued at its recent level of $145, he rates Intellia’s $43 stock at Outperform, given its teaming with Novartis, which is a big seller of sickle cell drugs.
Genetic treatments are cumbersome and still proving themselves. Drugs that relieve sickle cell symptoms are the first step for patients, and researchers will update ASH attendees on the Global Blood Therapeutics drug Oxbryta. Higher doses reduce sickling crises, according to one study, and the drug works in patients as young as 12.
Global Blood’s stock has fallen by nearly half this year, to a recent $44, with the company blaming Covid-19 for slowing its growth in the last couple of quarters. But RBC Capital Markets analyst Gregory Renza launched coverage Thursday with an Outperform rating, arguing that Oxbryta sales could grow from their current level of $150 million in annualized sales, to as much as $1.6 billion by decade’s end. His price target is $75.
His RBC colleague Kennen MacKay has an Outperform rating on Agios Pharmaceuticals. The Phase 3 success of the company’s drug mitapivat against a transfusion-necessitating disorder called Pyruvate Kinase Deficiency bodes well for mitapivat’s potential for treating other red cell disorders, wrote MacKay in a December 1 note. At ASH, researchers will present Phase 1 data showing the safety and benefits of mitapivat in eight sickle cell patients, and Phase 2 results in thalassemia. MacKay thinks Agios stock can rise from $45 to $66.
Write to Bill Alpert at [email protected]