Chronic leukemia

Beckman Coulter Life Sciences has received 510(k) clearance from the Food and Drug Administration (FDA) to distribute its DxFLEX Clinical Flow Cytometer in the United States. Launched regionally in 2020, this brings the popular benchtop IVD flow cytometry system to American labs while expanding testing capabilities. Offering up to 13-colours, additional detectors can be activated as laboratory needs evolve without the need to purchase additional hardware. “This pioneering advancement puts high-complexity flow cytometry testing within reach to more laboratories without added expense,” said Carsten Lange, product manager. “The DxFLEX Clinical Flow Cytometer adds more colours without adding more concerns, and enables laboratory staff to have greater confidence in results, while streamlining workflows and reducing manual steps. With more fluorescence parameters, laboratories can get more out of specimens and avoid a tedious compensation process and the burden that places on lab staff.” The compact DxFLEX Flow Cytometer makes multicolour flow cytometry less complex by using avalanche photodiode (APD) detector technology instead of traditional photomultiplier tube (PMT) technology. The use of APD technology simplifies compensation procedures and delivers richer content analysis with higher sensitivity to find dim populations. The compensation library simplifies compensation setup, while easy-to-learn CytExpert software lowers labour time and enables work to begin right out of the box for novice users. The compact DxFLEX Flow Cytometer is available in two configurations, from a three-laser/10-colour system to a three-laser/13- colour configuration. The DxFLEX Flow Cytometer is validated as an in vitro diagnostic device for 10-colour immunophenotyping with the ClearLLab 10C Reagent System and delivers the only FDA cleared and CE marked integrated leukemia and lymphoma solution, which offers all components needed, from quality controls, sample preparation and antibody panels to analysis software and training material. This enables workflows for diseases such as chronic leukemia, myeloma, acute leukemia, non-Hodgkin lymphoma, myeloproliferative neoplasm, and myelodysplastic syndrome.

Ionis Pharmaceuticals is continuing to study sapablursen in polycythemia vera. Lackluster midphase efficacy data have pushed Ionis Pharmaceuticals to trim its pipeline. The antisense specialist tossed out acromegaly prospect cimdelirsen and abandoned hopes of developing sapablursen in beta thalassemia. Both safety profiles were “clean, pristine,” Ionis CEO Brett Monia, Ph.D., said on a conference call with investors, adding that the decisions were “all about efficacy.” In acromegaly, Monia said Ionis saw “some reductions” in IGF-1—a growth factor found at elevated levels in patients with the rare hormonal disorder—in recipients of the antisense medicine cimdelirsen, but they fell short of the biotech’s minimum target product profile. “It wasn't good enough and, considering the richness of our pipeline, it just didn't clear the bar,” Monia said.  The CEO went on to discuss sapablursen, a drug candidate he called “more interesting.” In 2019, Ionis moved the prospect into a phase 2 trial in non-transfusion-dependent beta thalassemia intermedia, a milder form of the blood disease, on the strength of data in healthy volunteers that dialed up expectations at the company. In phase 1, Monia saw “quite remarkable” target engagement plus “very significant elevations in hepcidin levels.” However, “in beta-thalassemia intermedia, we didn't see those changes,” the CEO said.  Researchers have linked low levels of hepcidin to iron overload in beta thalassemia and have shown the hormone is negatively regulated by TMPRSS6. As such, Ionis bet that lowering TMPRSS6 would up-regulate hepcidin, alter iron metabolism and improve symptoms. But something went awry in the move into patients.  “TMPRSS6 is a pathway target; it's not a genetically validated target, keep that in mind. And we didn't see the biology translate from preclinical to clinical in that setting, so it didn't meet the product profile,” the CEO said. Ionis is continuing to study sapablursen in polycythemia vera, a type of chronic leukemia characterized by dysregulated iron metabolism. A phase 2 study in that indication kicked off in 2021 and is scheduled to wrap up next year.

Dive Brief:Treatment with Bristol Myers Squibbs CAR-T cell therapy Breyanzi led to remission in adults with chronic lymphoyctic leukemia, meeting the goal of a yearslong clinical trial and suggesting the complex drugs potential for use in patients with the slow-growing blood cancer.Bristol Myers did not disclose any specific data in its Thursday announcement of the positive study results, noting only that Breyanzi achieved the studys primary endpoint comparing treatment response rates to historical controls among certain patients with relapsed or refractory chronic lymphocytic leukemia.The company, which in early 2021 won U.S. approval of Breyanzi for lymphoma, said it will present detailed results at an upcoming medical conference as well as discuss with them with regulators.Dive Insight:CAR-T cell therapy is now an established treatment option for certain types of lymphoma and for acute lymphoblastic leukemia that has returned or become resistant to other drugs. The approvals of Breyanzi and therapies from Gilead Sciences and Novartis followed years of clinical testing by academic centers like the University of Pennsylvania, smaller biotechnology companies and, most recently, the large drugmakers that now own them.While none of those therapies are approved for chronic lymphocytic leukemia, or CLL, the blood cancer was the setting for one of the earliest demonstrations of CAR-T therapys powerful potential. More than a decade ago, researchers at UPenn used CAR-T therapy to treat CLL patients, leading to remissions that, in two individuals, have lasted more than ten years.The study of Breyanzi in CLL began in 2017, started by the treatments original biotech owner Juno Therapeutics. Initial results, presented at the American Society of Hematologys annual meeting the next year, showed the treatment led to responses in 13 of 16 patients with CLL or small lymphocytic leukemia who had previously been given the drug Imbruvica.By that time, however, Juno had been acquired by Celgene, which was primarily interested in Breyanzis potential in lymphoma. Celgene was then absorbed by Bristol Myers Squibb in a 2019 acquisition worth $74 billion.Now, more than five years after the Phase 1/2 study began, Bristol Myers is reporting Breyanzi met the primary goal of the Phase 2 portion of the trial. The study was open-label, meaning patients knew the treatment they received, and didnt include a control arm of patients who received placebo or another comparator drug.Bristol Myers noted complete responses to Breyanzi in a prespecified subset of CLL patients who were refractory to drugs like Imbruvica and previously treated with another kind of therapy known as a BCL-2 inhibitor.The company said there were no new safety signals reported for Breyanzi, which can cause dangerous immune reactions and neurological toxicity.In a population that has limited options, the ... study represents the first multicenter trial evaluating a CAR-T cell therapy in heavily pre-treated patients with relapsed or refractory CLL or SLL, with results showing the potential of Breyanzi as a personalized one-time treatment approach for patients with this difficult-to-treat disease, said Anne Kerber, head of cell therapy development at Bristol Myers, in the companys statement.Elsewhere, Novartis is testing a new type of CAR-T cell therapy together with Imbruvica in a Phase 1 CLL study that began in 2019, while Gilead has discontinued a study of its drug Tecartus in CLL. '