(This roundup of reports from the ASH 2024 convention first appeared in STAT’s “ASH in 30” e-newsletter. To get future editions, enroll right here.)
Greetings from the always-lovely San Diego. Adam Feuerstein, right here, and as you may see from the dawn photograph above, I’m nonetheless very a lot on East Coast time. (Good view from my lodge room, nevertheless.) I’ve traveled an ideal distance to deliver you information and evaluation from the annual assembly of the American Society of Hematology. And I’m not alone! Becoming a member of me are fellow STAT reporters (and West Coast denizens, all) Jonathan Wosen, Angus Chen, and Meghana Keshavan. Let’s roll.
Sanofi advances a brand new remedy for a uncommon, platelet-destroying illness
An oral remedy developed by the French pharma big Sanofi raised platelet counts and lowered bleeding episodes in sufferers with a uncommon autoimmune dysfunction that causes the physique to assault and destroy its personal blood-clotting platelets.
In a randomized, Part 3 examine, the Sanofi drug, known as rilzabrutinib, achieved an improved platelet response in 65% of members with persistent or continual immune thrombocytopenia (ITP) in comparison with 33% of members on a placebo. A sturdy platelet response was reported in 23% of the rilzabrutinib group in comparison with no sufferers within the management arm. The drug additionally confirmed reductions in bleeding episodes and enhancements in fatigue.
Rilzabrutinib is a bruton’s kinase (Btk) inhibitor, a sort of drug that’s accredited to be used in treating types of blood most cancers. However rilzabrutinib seems to be safer and higher tolerated than present medicines within the class, stated David Kuter, a doctor and director of hematology at Massachusetts Common Hospital, and an investigator within the Sanofi examine.
Many sufferers with extreme ITP obtain transient advantages from presently accessible remedies or don’t reply in any respect. The sturdiness of platelet responses seen with rilzabrutinib, he added, may assist set up the drug as a brand new commonplace remedy, Kuter added.
Sanofi has submitted rilzabrutinib to regulators within the U.S. and Europe, with a choice on a possible U.S. approval anticipated subsequent August.
A Novo Nordisk tablet appears to scale back extreme sickle cell ache crises
An oral drug from Novo Nordisk appeared to enhance the oxygen-carrying capability of pink blood cells and cut back the frequency of extreme ache crises skilled by sufferers with sickle cell illness. The Part 2 examine outcomes, if confirmed in a bigger examine, may result in a brand new approach of treating the debilitating blood illness that largely impacts individuals of African descent, together with Black Individuals.
Sixty members entered the examine experiencing a mean of three.3 extreme ache crises per yr. After one yr within the examine, the annualized fee of ache crises fell to only over one for members handled with Novo’s once-daily tablet, known as etavopivat, in comparison with just below two for members on a placebo.
‘What’s your ache proper now?’ Sickle cell, loss, and survival in America
Statistically, etavopivat lowered the prevalence of ache crises by 46% in comparison with a placebo, though the advance didn’t attain statistical significance. Etavopivat additionally elevated ranges of hemoglobin, the protein that helps pink blood cells carrying oxygen and improved a measure of fatigue, each relative to placebo. Complications, abdomen discomfort, and elevated liver enzymes had been essentially the most generally reported unwanted effects.
Etavopivat belongs to a category of medicine that activate an enzyme known as pyruvate kinase that pink blood cells use to transform sugars into vitality. The drug improves the well being of pink blood cells and slows their destruction.
“These outcomes are encouraging,” stated Julie Kanter, a doctor and director of the grownup sickle cell program on the College of Alabama at Birmingham. Kanter was an investigator within the etavopivat examine, and sees the drug, if finally accredited, as having the potential to turn into a normal remedy for the illness, alongside mainstay medicines like hydroxyurea.
Novo is conducting a bigger Part 3 examine of etavopivat in sickle cell illness with outcomes anticipated in 2026. Agios Prescription drugs is growing an analogous drug, known as mitapivat, additionally in a late-stage medical trial.
The regulatory bar within the U.S. for the approval of latest medication to deal with sickle cell illness has possible been raised after the current market withdrawal of Oxbrytra, a sickle cell drug from Pfizer, as a result of security issues. With Oxbryta, the FDA loosened its commonplace and granted approval based mostly on an enchancment in hemoglobin, alone.
Kanter stated she want to see drugmakers design research in sickle cell illness that use patient-reported outcomes, together with however not solely targeted on extreme ache crises, as a extra significant measure of total affected person profit.
Assessing a drug based mostly solely on the frequency of extreme ache crises that sends an individual to the hospital is tough to standardize as a result of people have completely different ranges of ache tolerance or entry to drugs and hospitals to deal with ache, Kanter stated.
Beam’s CRISPR remedy for sickle cell yields constant outcomes with extra sufferers
In additional sickle cell information, seven sufferers handled with a CRISPR-based remedy from Beam Therapeutics have all produced greater than 60% fetal hemoglobin, a wholesome, usually functioning type of the oxygen-carrying molecule. Corresponding ranges of sickled, or disease-causing, hemoglobin within the blood of all seven sufferers fell under 40%, Beam reported right now.
No sufferers have reported extreme ache crises since remedy with the Beam remedy, known as BEAM-101, though follow-up time stays comparatively brief.
Affected person dies in Beam Therapeutics trial of CRISPR sickle cell remedy
The up to date examine outcomes are in step with an evaluation performed on 4 sufferers that was reported in November.
BEAM-101 makes use of a more recent, gentler type of CRISPR, known as base enhancing. Base enhancing solely “nicks” DNA and adjustments a single letter, slightly than breaking a whole gene. The bottom-editing method may result in more healthy cells and better ranges of fetal hemoglobin, in comparison with an older model of CRISPR utilized by Vertex Prescription drugs in its accredited remedy, known as Casgevy.
As beforehand reported, a participant within the Beam examine died as a result of respiratory failure that was attributable to the poisonous chemotherapy routine required to arrange the bone marrow earlier than BEAM-101 could be administered.
Many sickle cell sufferers with extreme illness wrestle with a heart-wrenching dilemma : doubtlessly healing therapies carry the chance of infertility as a result of remedy regimens that precede these therapies. New analysis offered at ASH underscores that, within the fingers of skilled well being care suppliers, fertility preservation earlier than healing remedy is a viable choice for sufferers — supplied that they’ve entry to the process.
Researchers reviewed medical data on sickle cell sufferers throughout 5 remedy facilities who sought oocyte cryopreservation, during which a health care provider makes use of hormones to coax ovaries to launch immature eggs, or oocytes, that are then extracted and frozen. Out of 45 sufferers, 36 wanted solely a single cycle, whereas 5 wanted not less than two cycles of hormones due to a low cell yield the primary time.
The researchers additionally noticed that, basically, sufferers wanted increased ranges of the hormone gonadotropin to stimulate their ovaries in comparison with different younger adults present process the process, and but the ovaries of these with sickle cell nonetheless responded much less to the hormone. However the variety of oocytes retrieved and preserved was comparable between individuals with and with out the illness.
Almost half of the cryopreservation cycles had been related to a complication, together with 19 circumstances of ache crises after oocytes had been retrieved. Researchers discovered that having a complication was considerably extra possible amongst sufferers who’d had not less than three ache crises the yr earlier than.
“We are able to make this a secure process, and to not say that there received’t be issues equivalent to ache and repeat cycles,” stated Marti Goldenberg, a pediatric hematologist at Johns Hopkins and the examine’s first writer. “This is usually a nice choice for sufferers, so long as they’re recommended.”
A larger problem, she added, is that solely 21 states have legal guidelines requiring insurers to cowl fertility providers. Extra sickle cell sufferers are more likely to search these providers with the arrival of gene therapies from Vertex and CRISPR Therapeutics in addition to Bluebird Bio. Vertex filed a lawsuit in opposition to the U.S. authorities earlier this yr to permit the corporate to pay for fertility preservation providers for individuals receiving its remedy, a step that presently dangers violating federal regulation.
