Category Archives: Stem Cell Therapy

Long-term clinical trial data continues to support the use of axi-cel (axicabtagene ciloleucel) in treating patients with relapsed/refractory large B-cell lymphoma (LBCL), according to data presented at the 2022 Tandem Meeting.

Researchers presented five-year data from the phase 2 ZUMA-1 clinical trial, including the one- and two-year event-free survival findings.

In this updated five-year analysis, axi-cel induced long-term (overall survival) ... among treated patients, according to Dr. Caron A. Jacobson, the medical director of the Immune Effector Cell Therapy Program and senior physician at Dana-Farber Cancer Institute and an assistant professor of medicine at Harvard Medical School. She continued, Between the four- and five-year analysis, the time to next therapy curve remains stable and 92% of patients remained alive without a need for subsequent therapy, which may be suggestive of a cure in these patients.

Investigators reported a five-year overall survival rate of 42.6% following treatment with axi-cel. In the population of patients who experienced a complete response, the five-year overall survival rate was 64.4% and the median overall survival was not reached. Additionally, 63% of complete responders were alive at the five-year data cut off. At the four-year data cutoff, one patient died at month 63 and one experienced progressive disease at month 54.

To be considered for treatment, patients were required to have LBCL, including diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma or transformed follicular lymphoma. Patients were also required to have not responded to their last chemotherapeutic treatment or have relapsed 12 months or less following autologous stem cell transplant, which is a stem cell transplant using the patients own healthy cells. Treatment with a previous anti-CD20 monoclonal antibody and anthracycline was also necessary.

Those who underwent treatment received a conditioning regimen of cyclophosphamide and fludarabine for three days to get them ready for the main line of treatment. This was followed by axi-cel.

The main goal of the study was overall response rate with first response assessment four weeks following infusion. Key secondary end points included overall survival, safety and translational evaluations.

A total of 111 patients were enrolled on the study, eight of whom did not undergo treatment for one of the follow reasons: side effects (four patients), no measurable disease (two patients), death due to disease progression (one patient), and manufacturing failure (one patient); this left 103 patients to undergo conditioning. Of these patients, two were not treated due to side effects and death, respectively.

The data cutoff was Aug. 11, 2021 and the median follow-up was 63.1 months.

Additional findings from the trial highlighted a median time to next anticancer therapy of 8.7 months following infusion. A total of 34% of patients were alive at cutoff with no subsequent therapy or retreatment with axi-cel. Two patients who had prior progression underwent new anticancer therapy.

The five-year overall survival rates among those who had or had not experienced an event-free survival at month 12 were 5.3% vs 90.9%, respectively.

Events were classified as instances when the cancer recurred or became worse.

The median overall survival was 8.3 months among those who experienced an event and was not reached in those who did not experience an event. Additionally, the five-year overall survival rates among those who did or did not have an event at month 24 were 11.3% and 92.3%, respectively. Moreover, the median overall survival in both respective groups was 9.2 months and not reached.

Investigators also determined that early CAR-T cell expansion was associated with ongoing response at 60 months. The median peak CAR T levels appeared to be numerically higher in those who had an ongoing response at month 60 and lower in those who relapsed or did not respond to treatment. Similarly, another trend was observed in those who experienced CAR-T cell expansion by area under the curve from day 0 to 28.

A total of 58% of patients had died by the cutoff date. No new safety signals had been observed as of the five-year data cutoff, including serious side effects or secondary malignancies related to treatment.

Patients most commonly died due to progressive disease (45 patients), side effects (four patients), secondary malignancies (one patient) or other reasons (nine patients).

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Long-Term Axi-Cel Data 'May Be Suggestive of a Cure' in Patients With Large B-Cell Lymphoma - Curetoday.com

Cell therapy using induced pluripotent stem cell (iPSC) derivatives may result in abnormal tissue generation because the cells undergo numerous cycles of mitosis before clinical application, potentially increasing the accumulation of genetic abnormalities. Therefore, genetic tests may predict abnormal tissue formation after transplantation. Here, we administered iPSC derivatives with or without single-nucleotide variants (SNVs) and deletions in cancer-related genes with various genomic copy number variant (CNV) profiles into immunodeficient mice and examined the relationships between mutations and abnormal tissue formation after transplantation. No positive correlations were found between the presence of SNVs/deletions and the formation of abnormal tissues; the overall predictivity was 29%. However, a copy number higher than 3 was correlated, with an overall predictivity of 86%. Furthermore, we found CNV hotspots at 14q32.33 and 17q12 loci. Thus, CNV analysis may predict abnormal tissue formation after transplantation of iPSC derivatives and reduce the number of tumorigenicity tests.

Excerpt from:
Correlation Between Genetic Abnormalities in Induced Pluripotent Stem Cell-Derivatives and Abnormal Tissue Formation in Tumorigenicity Tests -...

Pooled data from 137 patients show Orca-T high-precision cell therapy improved overall survival and reduced chronic graft versus host disease compared to standard of care

Orca-T was well-tolerated and resulted in engraftment with regression of marrow fibrosis in patients with myelofibrosis

Manufacturing reliability analysis found vein-to-vein times for all grafts were under 72 hours regardless of donor collection site and transplant center locations

The Precision-T Phase 3 randomized registrational study of Orca-T versus standard of care is now open

MENLO PARK, Calif., April 25, 2022--(BUSINESS WIRE)--Orca Bio, a clinical-stage biotechnology company developing purified, high-precision cell therapies for the treatment of cancer, genetic blood disorders and autoimmune diseases, today announced that positive new data were presented at the 2022 Transplantation & Cellular Therapy ASTCT and CIBMTR Tandem Meetings in Salt Lake City, Utah.

The new data on Orca Bios lead investigational high-precision cell therapy, Orca-T, include updated results from 137 patients with hematologic malignancies, which continued to show an increase in overall survival rates and a reduction of acute and chronic graft versus host disease (GvHD) compared to standard of care; positive outcomes in a subset of patients with myelofibrosis who received Orca-T; and new analyses demonstrating Orca Bios manufacturing platform is reliable, robust and scalable.

"These data from an expanded group of patients are very encouraging and demonstrate that Orca-T appears to improve survival while reducing GvHD. This could be a compelling option for patients battling serious hematological malignancies who currently face devastating transplant-related risks," said Everett Meyer, M.D., Ph.D., primary investigator. "These results, combined with the reliable and centralized Orca-T manufacturing, could potentially transform treatment options for patients and physicians."

Story continues

Orca Bio presented pooled data from 137 patients in the single-center Phase 2 and multi-center Phase 1b trials of Orca-T with acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL) and myelodysplastic syndromes (MDS), with at least 100 days of follow-up and a median of 341 days. For comparison purposes, an independent CIBMTR-based control arm was identified, consisting of similar patients with hematologic malignancies who received a standard of care allogeneic hematopoietic stem cell transplant ("alloHSCT") over a similar timeframe. Results demonstrated that:

Rates of moderate-to-severe chronic GvHD were low among Orca-T recipients, occurring in only 5% of patients at one year compared to 38% who received a standard alloHSCT.

GvHD-free, relapse-free survival (GRFS) was 71% at one year for Orca-T patients compared to 21% in the CIBMTR-based control arm.

The overall survival for patients who received Orca-T was 90% at one year compared to 68% in the CIBMTR-based control arm.

Additionally, Orca Bio presented findings from a manufacturing reliability analysis of 100 Orca-T products in the Phase 1b trial. All investigational cell therapies were manufactured at Orca Bios cGMP facility in Sacramento, CA, and transplant centers and donor sites were located across the U.S. All products were successfully delivered and infused to patients within 72 hours or less.

"We produce a unique batch of drug for each patient who receives an Orca-T product, and this drug is made up of fresh, living cells that need to be infused on an extremely rapid timeline," said Nate Fernhoff, Ph.D., co-founder and chief scientific officer at Orca Bio. "Reliable and scalable manufacturing have been integral to the development of our therapies since day one. These results not only show that Orca-T continues to reduce GvHD and improve survival rates over time, but that we have maintained the ability to reliably manufacture, deliver and infuse all patients in a timely manner regardless of donor and patient location. This is an important indication of our ability to potentially deliver this therapy urgently and seamlessly to patients in need."

In a separate poster, Orca Bio presented updated data on the treatment impact of Orca-T in 12 patients with myelofibrosis compared to nine patients who received a standard of care alloHSCT. Orca-T recipients had lower incidence of acute and chronic GvHD (33% with Orca-T versus 100% with alloHSCT) and the data suggest Orca-T was well-tolerated. Treatment with Orca-T resulted in engraftment with regression of marrow fibrosis, indicating potential efficacy for the treatment of myelofibrosis.

Based on the favorable results of the Phase 1b and 2 clinical trials, a randomized registrational Phase 3 trial evaluating Orca-T against standard of care alloHSCT, named Precision-T, is now open. More details will be announced in the coming weeks.

Links to the abstracts follow:

Title: Orca-T Demonstrates Encouraging Overall Survival, Gvhd Reduction, and Tolerability in Patients with Hematologic Malignancies Poster Number: 412

Title: Outcomes for Myelofibrosis Patients Following Myeloablative Allogeneic Stem Cell Transplantation Using the Orca-T Graft from HLA-Matched Related and Unrelated Donors Poster Number: 413

Title: Manufacture and Distribution of High-Precision Orca-T Is Reliable, Robust, and Scalable Poster Number: 415

About Orca-TOrca-T is an investigational high-precision allogeneic cellular therapy consisting of infusions containing regulatory T-cells, conventional T-cells and CD34+ stem cells derived from peripheral blood from either related or unrelated matched donors. Orca-T has received Regenerative Medicine Advanced Therapy (RMAT) designation from the U.S. Food and Drug Administration and is being studied to treat multiple hematologic malignancies.

About Orca BioOrca Bio is a clinical-stage biotechnology company developing purified, high-precision cell therapies for the treatment of cancer, genetic blood disorders and autoimmune diseases. Our investigational therapies are designed to deliver better survival rates with dramatically fewer risks than standard allogeneic stem cell transplants, like graft versus host disease and other debilitating transplant-related toxicities. At Orca Bio, we hope to not only replace patients' blood and immune systems with healthy ones, but restore their quality of life. For more information, visit http://www.orcabio.com and follow Orca Bio on Twitter: @orcabio.

View source version on businesswire.com: https://www.businesswire.com/news/home/20220425005162/en/

Contacts

Corporate CommunicationsKelsey Grossmanmedia@orcabio.com

Investor RelationsJoshua Murrayir@orcabio.com

Excerpt from:
Orca Bio Presents Positive Data Reinforcing Clinical Profile and Manufacturing Reliability of Orca-T at 2022 Transplantation & Cellular Therapy...

Chronic myeloid leukemia (CML) blast crisis phase is the last stage of the condition where there are large clusters of immature white blood cells, or blasts, in the bone marrow, organs, and tissue.

CML progresses in phases, starting with the chronic phase, accelerated phase, and the blast crisis phase, the last stage of this condition.

Doctors define which phase a person has by the number of blasts in the bone marrow and blood. In the blast crisis phase, blood or bone marrow samples show 20% or more blasts. In this phase, large clusters of blasts present in the bone marrow, organs, and tissue.

This article discusses what CML blast crisis is, its symptoms, and treatment options. It also looks at the outlook for a person with this phase of CML and provides a brief overview of other phases of this condition.

CML is a form of cancer that affects blood-forming cells in the bone marrow. The blood-forming cells will normally become red and white blood cells and platelets. If a person has CML, immature white blood cells, or blasts, grow uncontrollably in the bone marrow at a higher rate than other types of blood cells.

Learn more about how doctors diagnose CML.

Healthy bone marrow contains 5% blasts, meaning a person will have five blasts for every 100 blood cells. During the first phase of CML, the chronic phase, the number of blasts increases but remains at less than 15%. CML progresses slowly and can take months or years to progress to the next phase.

During the accelerated phase of CML, the second phase, the number of blasts is higher. There may also be more white blood cells and fewer platelets. During the accelerated phase of CML, CML cells may grow quickly, and there may be mutations within other cells.

Blast crisis is the third and final stage of CML. This phase can occur after resistance to targeted therapy and due to additional gene mutations.

During this phase, the number of blasts is very high, at around 30%, meaning three in every 10 cells are blast cells. Blasts may also be present in organs and tissues outside the blood and bone marrow.

The blast crisis phase of CML is more difficult to treat and can be life threatening.

There are various symptoms of CML. A person may experience any of the following:

However, these symptoms may also be a result of several conditions, including other cancers.

Several symptoms can indicate a shortage of blood cells. People with CML may experience these symptoms as the blasts replace red and white blood cells and platelets:

If a person experiences any symptoms of CML, they should contact a doctor as soon as possible.

A person with blast crisis phase CML will likely receive treatment at a specialized center with experts in treating this condition.

Healthcare professionals will order two tests before deciding on treatment for blast crisis CML.

Doctors will need to determine whether the blast phase involves myeloid or lymphoid blast cells, which will influence the method of treatment they offer.

Additionally, people will need to undergo a CBR-ABL1 kinase domain mutation analysis, which checks for mutations in the gene that tyrosine kinase inhibitor (TKI) therapy targets. Certain mutations can make the protein in the gene more or less resistant to TKI therapy.

Treatment may include:

Learn more about treatment for CML.

Without treatment, CML can be fatal in the blast crisis phase, with a median survival rate of approximately 23 years. However, research suggests that new therapies mean that, on average, people with CML will die 3 years earlier than those without CML.

According to the American Cancer Society, several factors can negatively affect a persons outlook, such as:

Doctors will consider these factors when using the Sokal system, which develops a score to help predict a persons outlook. This system can categorize people into low, intermediate, or high risk groups.

Healthcare professionals may also use the Euro score system, which considers the percentage of eosinophils and basophils in the blood. More of these cells can indicate a worse outlook.

There are two other phases of CML: the chronic phase and the accelerated phase.

Learn more about the phases of CML.

The chronic phase is the first stage of CML.

A person may experience mild symptoms or none at all. People with this phase of CML will have a blast content under 10%. Most individuals in this stage respond well to treatments.

The accelerated phase is the second stage of CML.

A doctor is likely to diagnose a person with this stage of CML if:

People with the accelerated phase of CML may experience symptoms such as fever, weight loss, and loss of appetite. Individuals typically do not respond as well to treatment as those with chronic phase CML.

Blast crisis phase is the third and final stage of chronic myeloid leukemia, a form of cancer where large amounts of immature white blood cells grow in the bone marrow, blood, organs, and tissue.

Without treatment for blast crisis CML, this condition is fatal, with a survival rate of around 23 years. Doctors will consider several factors, such as a persons age and the phase of cancer, when calculating the outlook.

Treatment options include targeted therapy, stem cell transplants, and chemotherapy. Healthcare professionals will conduct tests to determine which treatment best suits each individual.

Excerpt from:
CML blast crisis phase: Definition, symptoms, and more - Medical News Today

Primary endpoint is the reduction in hemorrhoidal symptoms

CRANFORD, N.J., April 26, 2022 /PRNewswire/ -- Citius Pharmaceuticals, Inc. ("Citius" or the "Company") (Nasdaq: CTXR), a late-stage biopharmaceutical company developing and commercializing first-in-class critical care products,today announced that the first patient has been enrolled in the Company's Phase 2b clinical study of Halo-Lido for the treatment of hemorrhoids. If approved, Halo-Lido would be the first FDA-approved prescription product indicated for the treatment of hemorrhoids.

The Phase 2b study is a multi-center, randomized, dose-ranging, double-blind, parallel group comparison clinical trial. Five cohorts of adults with a clinical diagnosis of symptomatic Goligher's classification Grade II or Grade III hemorrhoids will be dosed. Approximately 60 patients per cohort are expected to be enrolled, for a total of 300 patients.

The key objective of the study is to evaluate the ability of the formulations used in each cohort to provide relief for patients with acute flare ups. The study will evaluate reduction in hemorrhoidal symptoms (including: pain, burning, itching, and swelling) following treatment and is expected to provide the foundation for development of the Phase 3 study. The FDA has guided Citius in developing a Patient Reported Outcome (ePRO) instrument which patients will use to record and report important safety and efficacy data in real time. The instrument has been adapted for use on an electronic platform and will be loaded on patients' hand-held smart devices. The study will also be used to validate the ePRO. Results of this trial are expected in the second half of 2023.

"We are pleased to have initiated the Halo-Lido study and expect to complete enrollment later this year. Currently, there are no FDA-approved prescription-strength treatments available to the millions of adults who suffer from hemorrhoid discomfort each year. If approved, Halo-Lido would be the first prescription product indicated for the treatment of hemorrhoids. As such, we believe there is a substantial worldwide market opportunity for this drug candidate. Assuming study results are positive, and in order to realize the full potential of Halo-Lido, we intend to seek strategic or financial partners for this asset at the appropriate time," stated Leonard Mazur, Executive Chairman of Citius.

About Halo-Lido

Halo-Lido is a proprietary topical formulation of halobetasol and lidocaine that is intended to provide symptomatic relief to individuals suffering from hemorrhoids. Hemorrhoids are a gastrointestinal disorder characterized by pain, swelling, itching, tenderness, and bleeding. Although hemorrhoids are not life-threatening, individual patients often suffer painful symptoms that can limit social activities and have a negative impact on the quality of life. More than half of the U.S. population will experience hemorrhoidal disease at least once in their life. Each year, nearly 10 million patients in the U.S. report symptoms.

About Citius Pharmaceuticals, Inc.

Citius is a late-stage biopharmaceutical company dedicated to the development and commercialization of first-in-class critical care products, with a focus on oncology, anti-infectives in adjunct cancer care, unique prescription products, and stem cell therapies. The Company has two late-stage product candidates, Mino-Lok, an antibiotic lock solution for the treatment of patients with catheter-related bloodstream infections (CRBSIs), which is currently enrolling patients in a Phase 3 Pivotal superiority trial, and I/ONTAK (E7777), a novel IL-2R immunotherapy for an initial indication in cutaneous T-cell lymphoma (CTCL), which has completed enrollment in its Pivotal Phase 3 trial. Mino-Lokwas granted Fast Track designation by the U.S. Food and Drug Administration (FDA). I/ONTAK has received orphan drug designation by the FDA for the treatment of CTCL and peripheral T-cell lymphoma (PTCL). Through its subsidiary, NoveCite, Inc., Citius is developing a novel proprietary mesenchymal stem cell treatment derived from induced pluripotent stem cells (iPSCs) for acute respiratory conditions, with a near-term focus on acute respiratory distress syndrome (ARDS) associated with COVID-19. For more information, please visit http://www.citiuspharma.com.

Safe Harbor

This press release may contain "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Such statements are made based on our expectations and beliefs concerning future events impacting Citius. You can identify these statements by the fact that they use words such as "believe," "anticipate," "estimate," "expect," "plan," "should," and "may" and other words and terms of similar meaning or use of future dates. Forward-looking statements are based on management's current expectations and are subject to risks and uncertainties that could negatively affect our business, operating results, financial condition and stock price. Factors that could cause actual results to differ materially from those currently anticipated are: our ability to successfully undertake and complete clinical trials and the results from those trials for our product candidates; the estimated markets for our product candidates and the acceptance thereof by any market; the ability of our product candidates to impact the quality of life of our target patient populations; risks relating to the results of research and development activities, including those from existing and new pipeline assets; uncertainties relating to preclinical and clinical testing; our need for substantial additional funds; the early stage of products under development; our dependence on third-party suppliers; our ability to commercialize our products if approved by the FDA; market and other conditions; our ability to attract, integrate, and retain key personnel; risks related to our growth strategy; patent and intellectual property matters; our ability to obtain, perform under and maintain financing and strategic agreements and relationships; our ability to identify, acquire, close and integrate product candidates and companies successfully and on a timely basis; our ability to procure cGMP commercial-scale supply; government regulation; competition; as well as other risks described in our SEC filings. These risks have been and may be further impacted by Covid-19. Accordingly, these forward-looking statements do not constitute guarantees of future performance, and you are cautioned not to place undue reliance on these forward-looking statements. Risks regarding our business are described in detail in our Securities and Exchange Commission ("SEC") filings which are available on the SEC's website at http://www.sec.gov, including in our Annual Report on Form 10-K for the year ended September 30, 2021, filed with the SEC on December 15, 2021 and updated by our subsequent filings with the SEC. These forward-looking statements speak only as of the date hereof, and we expressly disclaim any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in our expectations or any changes in events, conditions or circumstances on which any such statement is based, except as required by law.

Investor Relations for Citius Pharmaceuticals:

Ilanit AllenVice President, Investor Relations and Corporate CommunicationsT: 908-967-6677 x113E: [emailprotected]

SOURCE Citius Pharmaceuticals, Inc.

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Citius Pharmaceuticals Enrolls First Patient in Phase 2b Study of Halo-Lido for the Prescription Treatment of Hemorrhoids - PR Newswire

NEW YORK and HONG KONG, April 26, 2022 /PRNewswire/ --Treadwell Therapeutics, a clinical-stage biotechnology company developing novel medicines for unmet needs in cancer, announced today that the U.S. Food and Drug Administration (FDA) has granted Fast Track Designation to CFI-400945, a first in class inhibitor of Polo-like kinase 4 (PLK4), for the treatment of adult patients with relapsed or refractory Acute Myeloid Leukemia (AML).

"Although several exciting new classes of medicines have emerged in the past decade for patients with AML, there still remains an unmet need for certain patient segments, where survival rates remain low," said Dr. Michael Tusche, Treadwell co-CEO. "CFI-400945, has shown encouraging signs of monotherapy activity in AML patients with adverse cytogenetics. We are grateful for the Fast Track Designation for this exciting program, and look forward to frequent interactions with the FDA to chart our regulatory path forward, as we continue the development of '945 in leukemia."

Fast Track designation seeks to streamline the development and accelerate the review of new agents with potential to treat serious or life-threatening diseases and that potentially address an unmet medical need. Drugs that are granted this designation can have more frequent interactions with the FDA, as well as potential pathways for expedited approval.

About AML

AML is a disease characterized by uncontrolled proliferation of malignant clonal hematopoietic stem cells which can lead to anemia, neutropenia, and thrombocytopenia. If left untreated, AML can lead to death within weeks. In the US, an estimated 19,940 new cases of AML were expected to be diagnosed and approximately 11,180 deaths attributed to AML, nearly all in adults. AML is generally a disease of the elderly with an average age of 68 years at the time of diagnosis and is more common in men than women. For adults <65 years of age, the 5-year survival is approximately 33%, but drops dramatically to 4% in adults >65 years of age.

About Treadwell TherapeuticsTreadwell Therapeutics is a clinical-stage multi-modality oncology company developing novel medicines to address unmet needs in patients with cancer. The Company's robust, internally developed clinical pipeline includes CFI-400945, CFI-402257 (TTK inhibitor) and CFI-402411 (HPK1 inhibitor). Treadwell also has a robust pre-clinical pipeline with multiple biologic and next generation TCR based autologous cell therapy programs. For more information, please visit http://www.treadwelltx.com.

Contact[emailprotected]

SOURCE Treadwell Therapeutics

Link:
Treadwell Therapeutics Announces Fast Track Designation Granted by the FDA to CFI-400945 for the Treatment of Acute Myeloid Leukemia - PR Newswire