Retinoblastoma

FDA-approved generic provides cost-effective option for treating cancer LAKE ZURICH, Ill.--(BUSINESS WIRE)-- Fresenius Kabi announced today it has introduced Cyclophosphamide for Injection, USP, a generic substitute for Cytoxan, for use in treating several forms of cancer. Now available in the U.S., Cyclophosphamide for Injection, USP is the newest addition to Fresenius Kabi’s broad portfolio of generic oncology injectables that help make cancer therapies more affordable and accessible. This press release features multimedia. View the full release here: Cyclophosphamide is now available from Fresenius Kabi. (Photo: Business Wire) “The introduction of Cyclophosphamide for Injection adds another critical treatment to our broad and leading oncology portfolio that offers lower-cost options for treating cancer,” said John Ducker, president and CEO of Fresenius Kabi USA. Supplied as a 500mg, 1g, and 2g single-dose vials of lyophilized powder, the drug can be administered intravenously or orally. Fresenius Kabi offers all lyophilized presentations of cyclophosphamide currently in the market. Cyclophosphamide for Injection, USP is available through distributors or direct from Fresenius Kabi. About Cyclophosphamide for Injection, USP Cyclophosphamide for Injection is an alkylating drug indicated for the treatment of: Malignant Diseases: malignant lymphomas: Hodgkin's disease, lymphocytic lymphoma, mixed-cell type lymphoma, histiocytic lymphoma, Burkitt's lymphoma; multiple myeloma, leukemias, mycosis fungoides, neuroblastoma, adenocarcinoma of ovary, retinoblastoma, breast carcinoma Minimal Change Nephrotic Syndrome in Pediatric Patients: biopsy proven minimal change nephrotic syndrome patients who failed to adequately respond to or are unable to tolerate adrenocorticosteroid therapy Limitations of Use: The safety and effectiveness for the treatment of nephrotic syndrome in adults or other renal disease has not been established. IMPORTANT SAFETY INFORMATION Cyclophosphamide for Injection is contraindicated in patients with hypersensitivity to cyclophosphamide and with urinary outflow obstruction. Myelosuppression, Immunosuppression, Bone Marrow Failure and Infections - Severe immunosuppression may lead to serious and sometimes fatal infections. Close hematological monitoring is required. Urinary Tract and Renal Toxicity - Hemorrhagic cystitis, pyelitis, ureteritis, and hematuria can occur. Exclude or correct any urinary tract obstructions prior to treatment. Cardiotoxicity - Myocarditis, myopericarditis, pericardial effusion, arrhythmias and congestive heart failure, which may be fatal, have been reported. Monitor patients, especially those with risk factors for cardiotoxicity or pre-existing cardiac disease. Pulmonary Toxicity - Pneumonitis, pulmonary fibrosis and pulmonary veno-occlusive disease leading to respiratory failure may occur. Monitor patients for signs and symptoms of pulmonary toxicity. Secondary malignancies have been reported in patients treated with cyclophosphamide-containing regimens. Veno-occlusive Liver Disease - Fatal outcome can occur. Embryo-Fetal Toxicity - Can cause fetal harm. Advise female patients of reproductive potential to avoid pregnancy. Adverse reactions reported most often include neutropenia, febrile neutropenia, fever, alopecia, nausea, vomiting, and diarrhea. To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Kabi USA, LLC at 1-800-551-7176, option 5, or FDA at 1-800-FDA-1088 or . Nursing Mothers: Discontinue drug or nursing. Females and males of reproductive potential: Counsel patients on pregnancy prevention and planning. Renal Patients: Monitor for toxicity in patients with moderate and severe renal impairment. This Important Safety Information does not include all the information needed to use Cyclophosphamide for Injection, USP safely and effectively. Please see the full prescribing information for Cyclophosphamide for Injection, USP at . About Fresenius Kabi Fresenius Kabi ( ) is a global health care company that specializes in injectable medicines, biosimilars, clinical nutrition and technologies for infusion and transfusion. The company’s products and services are used to help care for patients with critical and chronic conditions. The company’s U.S. headquarters is in Lake Zurich, Illinois. The company’s global headquarters is in Bad Homburg, Germany. To learn about U.S. career opportunities at Fresenius Kabi, visit us at and follow us on LinkedIn and Facebook.

Feb. 07, 2024 -- Theriva™ Biologics (NYSE American: TOVX), a diversified clinical-stage company developing therapeutics designed to treat cancer and related diseases in areas of high unmet need, today announced that the Independent Data Monitoring Committee (IDMC) recommended the continuation of enrollment as planned into VIRAGE, a multinational, Phase 2b, randomized, open-label, controlled clinical trial evaluating VCN-01 in combination with standard-of-care chemotherapy (gemcitabine/nab-paclitaxel) as a first-line therapy for patients with metastatic pancreatic ductal adenocarcinoma (PDAC). According to the IDMC's comprehensive assessment of clinical data from patients enrolled across 6 sites open in the U.S. and 9 sites open in Spain, the ongoing Phase 2b trial will continue without any changes to the protocol. No safety concerns were raised based on the evaluation of data presented at the IDMC meeting. Intravenous VCN-01 has been well tolerated and demonstrated a safety profile consistent with prior clinical trials. Importantly, no additional toxicities were observed in patients receiving a second dose of VCN-01, providing the first clinical evidence of the feasibility of repeated systemic dosing. VIRAGE remains on track to complete enrollment in the first half of 2024. "The positive IDMC review of VCN-01 safety following repeated systemic dosing marks a significant step forward for our lead program. VCN-01 is a highly differentiated, systemic, selective, stroma-degrading oncolytic adenovirus," said Steven A. Shallcross, Chief Executive Officer of Theriva Biologics. “With the IDMC’s recommendation, we will continue to drive forward the VIRAGE study and explore the potential of VCN-01 to improve outcomes in first-line metastatic PDAC patients treated with standard-of-care chemotherapy. We have shown that repeated systemic dosing of VCN-01 is feasible from a safety perspective, and can now focus on whether the repeated-dose VCN-01 regimen may lead to improved clinical outcomes for patients with PDAC and other solid cancers.” VIRAGE is a two-arm Phase 2b open-label, randomized, controlled, multicenter clinical trial in patients with histologically confirmed, newly-diagnosed metastatic PDAC. VIRAGE is expected to enroll up to 92 adult participants at up to 25 sites across the US and Spain. In both the control and treatment arms, patients will receive gemcitabine/nab-paclitaxel standard-of-care chemotherapy over 28-day cycles. In the treatment arm only, patients will also receive systemically administered VCN-01 seven-days prior to the first and fourth cycles of gemcitabine/nab-paclitaxel treatment. Primary endpoints for the trial include overall survival and VCN-01 safety/tolerability. Additional endpoints include progression free survival, objective response rate, and measures of biodistribution, VCN-01 replication, and immune response. Since this is an open-label trial, progress will be monitored very closely and steps to accelerate the clinical program may be implemented if supported by the emerging data. More information about the trial is available on Clinicaltrials.gov (NCT05673811), through the Spanish Clinical Trials Registry and European Union Drug Regulating Authorities Clinical Trials Database (EudraCT Number: 2022-000897-24). VCN-01 is a systemically administered oncolytic adenovirus designed to selectively and aggressively replicate within tumor cells and degrade the tumor stroma that serves as a significant physical and immunosuppressive barrier to cancer treatment. This unique mode-of-action enables VCN-01 to exert multiple antitumor effects by (i) selectively infecting and lysing tumor cells; (ii) enhancing the access and perfusion of co-administered chemotherapy products; and (iii) increasing tumor immunogenicity and exposing the tumor to the patient’s immune system and co-administered immunotherapy products. Systemic administration enables VCN-01 to exert its actions on both the primary tumor and metastases. VCN-01 has been administered to over 80 patients in Phase 1 and investigator-sponsored clinical trials of different cancers, including PDAC (in combination with chemotherapy), head and neck squamous cell carcinoma (with an immune checkpoint inhibitor), ovarian cancer (with CAR-T cell therapy), colorectal cancer, and retinoblastoma (by intravitreal injection). Theriva™ Biologics (NYSE American: TOVX), is a diversified clinical-stage company developing therapeutics designed to treat cancer and related diseases in areas of high unmet need. The Company is advancing a new oncolytic adenovirus platform designed for intravenous (IV), intravitreal and antitumoral delivery to trigger tumor cell death, improve access of co-administered cancer therapies to the tumor, and promote a robust and sustained anti-tumor response by the patient’s immune system. The Company’s lead candidates are: (1) VCN-01, an oncolytic adenovirus designed to replicate selectively and aggressively within tumor cells, and to degrade the tumor stroma barrier that serves as a significant physical and immunosuppressive barrier to cancer treatment; (2) SYN-004 (ribaxamase) which is designed to degrade certain commonly used IV beta-lactam antibiotics within the gastrointestinal (GI) tract to prevent microbiome damage, thereby limiting overgrowth of pathogenic organisms such as VRE (vancomycin resistant Enterococci) and reducing the incidence and severity of acute graft-versus-host-disease (aGVHD) in allogeneic hematopoietic cell transplant (HCT) recipients; and (3) SYN-020, a recombinant oral formulation of the enzyme intestinal alkaline phosphatase (IAP) produced under cGMP conditions and intended to treat both local GI and systemic diseases. For more information, please visit Theriva Biologics’ website at www.therivabio.com. 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While Daiichi Sankyo's DS-7300a has been shown to be effective in interim human data from early trials on the drug in castration-resistant prostate cancer, there’s reason to think that it might not work as well on its own in some subtypes. New preclinical research on Daiichi Sankyo’s antibody-drug conjugate DS-7300a suggests it might be more effective against hard-to-treat forms of prostate cancer when used alongside a long-standing chemotherapy drug. According to the results of a study published Nov. 15 in Science Translational Medicine, experiments assessing DS-7300a with and without the blood cancer chemo agent decitabine found that the combo was more effective in mice with neuroendocrine prostate cancer (NEPC) and a form where the tumor suppressor gene RB1 is mutated or lost. The research was sponsored in part by the Japanese pharma and performed by scientists at the Dana-Farber Cancer Institute. In general, prostate cancer is one of the most treatable if detected early. But some advanced types require castration, where hormones or surgery are used to lower testosterone levels and stop the cancer from growing. About 10% to 20% are resistant to treatment with castration—and, of these, a relatively high number have either changes to RB1 or have evolved into NEPC, both of which make them especially tough to treat. “RB1 genomic loss is uncommon at prostate cancer diagnosis but RB1 deletion or mutation is present in approximately 10 to 20% of castration-resistant prostate cancers,” lead author Himisha Beltran, M.D., a genitourinary oncologist and director of translational research within medical oncology at Dana-Farber, explained to Fierce Biotech Research via email. NEPC makes up another 15 to 20%, she added. Both scenarios make the prognosis far more dire. Beltran’s team had previously identified changes in DNA that distinguish NEPC from other forms of prostate cancer, including some that resulted in higher production of enzymes called DNA methyltransferases. Now, they wanted to find out how these DNA changes—also known as DNA methylation—made prostate cancer harder to treat and whether the most highly expressed DNA methyltransferases, DNMT1 and DNMT3A, might be a viable drug target. For that, they turned to decitabine, a chemotherapy drug that has been used for myelodysplastic cancers since the 1980s. Its anti-cancer activity stems from its ability to inhibit DNA methyltransferases, including DNMT1 and DNMT3A. Studies on NEPC patient-derived cell lines and organoids showed the drug could effectively kill cancer cells, findings that were validated in mouse models of the disease. They also saw differences in DNA markers between treated and untreated mouse models that indicated the drug was effectively preventing DNA methylation. These findings led the researchers to wonder whether the benefit from using decitabine to inhibit DNMT1 and DNMT3a could extend beyond NEPC to remedy other types of DNA changes found in advanced prostate cancer. They homed in on RB1, the deletion or mutation of which makes the disease more resistant to treatment as well as more likely to evolve into NEPC. Cell studies and experiments with a mouse model of prostate cancer without the RB1 gene showed that the drug was effective in inhibiting tumor progression, though it didn’t have an effect on cancer in models where the gene was intact. Additional analysis showed that, like in the case of NEPC, it worked by inhibiting the DNMTs. Knowing that DNMT inhibition could lead to the expression of other cancer cell genes, the researchers next focused on seeing whether any of them might make good targets for a combination treatment with decitabine. RNA and DNA sequencing analysis gave them 245 potential candidates, one of which stood out as having some ideal characteristics: the gene for a receptor called B7-H3, the target of prostate tumor treatments under investigation including DS-7300a. While DS-7300a has been shown to be effective in interim human data (PDF) from early trials on the drug in castration-resistant prostate cancer, there’s reason to think that it might not work as well in NEPC or RB1-mutated tumors. That’s because those forms have lower expression of B7-H3 than other types, research shows, which could make them less vulnerable to the drug. Beltran’s lab reasoned that treating NEPC and RB1-mutated tumors with decitabine might make them more susceptible to DS-7300a by raising levels of B7-H3. After showing through cell studies that the combination of decitabine and DS-7300a was indeed synergistic—and that DS-7300a alone wasn’t as effective against cancer cells where B7-H3 expression was low—the researchers tested it out in mouse models. Just as they saw in vitro, DS-7300a had anti-tumor effects in mice with both high- and low-B7-H3-expressing tumors but was more effective against tumors with low levels of B7-H3 when combined with decitabine. The study comes with caveats. It only looked at a limited number of prostate cancer models, the researchers wrote in their report, so it couldn’t assess all the possible relationships between DNA methylation, gene expression and treatment response according to a prostate cancer’s specific genotype and phenotype. On top of that, it’s not clear what level of B7-H3 should be expressed by tumors for them to respond to therapy, Beltran noted. “This can be investigated further in ongoing trials,” she said. Beltran’s team plans to study whether NEPC and prostate cancers with the loss of RB1 respond to monotherapy with decitabine in clinical trials. They also hope to launch a study on the drug in combination with DS-7300a, the effectiveness of which will be assessed in part according to certain biomarkers, she said.