On November 18, 2022 Jazz Pharmaceuticals plc (Nasdaq: JAZZ) reported the U.S. Food and Drug Administration (FDA) approval of a supplemental Biologics License Application (sBLA) to add a Monday/Wednesday/Friday (MWF) intramuscular (IM) dosing schedule for Rylaze (asparaginase erwinia chrysanthemi (recombinant)-rywn) (Press release, Jazz Pharmaceuticals, NOV 18, 2022, View Source [SID1234624252]). Rylaze is approved for use in the U.S. as a component of a multi-agent chemotherapeutic regimen for the treatment of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) in adult and pediatric patients one month or older who have developed hypersensitivity to E. coli-derived asparaginase.

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Rylaze was first approved in the U.S. in June 2021 under the FDA Real-Time Oncology Review (RTOR) program. The approval with a dosing schedule of 25 mg/m2 administered IM every 48 hours met the immediate patient need for a non-E.coli-derived asparaginase treatment option while the clinical trial was still ongoing to evaluate additional dosing and administration options.

"With the addition of a Monday/Wednesday/Friday dosing schedule for Rylaze, patients will have another dosing option, which provides sustained asparaginase activity throughout the entire course of Rylaze treatment," said Rob Iannone, M.D., M.S.C.E., executive vice president, global head of research and development of Jazz Pharmaceuticals. "Jazz has been consistently committed to ensuring access to the reliable, high-quality supply of this important therapy so patients and healthcare providers have the opportunity to complete the full course of asparaginase therapy. As part of our efforts to improve patient and healthcare provider experience with Rylaze, we have evaluated additional dosing and administration options, and are also seeking approval for Rylaze globally."

"The expansion of the Rylaze label to include a Monday/Wednesday/Friday dosing schedule provides another option to support patients in completing their planned asparaginase treatment regimen. The benefit of completing the full course of asparaginase has been shown in various publications, and discontinuation of asparaginase has been associated with inferior disease-free survival," said Dr. Luke Maese, associate professor at the University of Utah, Primary Children’s Hospital and Huntsman Cancer Institute. "Rylaze is an effective and reliable treatment option for patients with ALL and LBL that have developed hypersensitivity to an E. coli-derived asparaginase."

The MWF dosing option was approved by the FDA under the RTOR program based on data from the intramuscular administration part of the Phase 2/3 trial (JZP458-201 or AALL1931), which was developed and conducted in close collaboration with the Children’s Oncology Group (COG) and was the basis for the initial approval of Rylaze in June 2021.

Results show that a dosing regimen of 25 mg/m2 administered intramuscularly on Monday morning and Wednesday morning, and 50 mg/m2 administered on Friday afternoon demonstrated a positive benefit-to-risk profile, with ≥90% of the patients achieving nadir serum asparaginase activity (NSAA) ≥0.1 U/mL by simulation.1

Overall, the safety profile of Rylaze was consistent with the reported safety information for patients with ALL/LBL receiving asparaginase with combination chemotherapy. There were no new safety signals observed in the trial.1

Rylaze was granted orphan drug designation for the treatment of ALL/LBL in June 2021 and was added to the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines) in July 2021. Jazz also completed the submission of an sBLA to the FDA seeking approval for an intravenous route of administration for Rylaze as well as the submission of a Marketing Authorisation Application (MAA) to the European Medicines Agency for JZP458.

About Rylaze (asparaginase erwinia chrysanthemi (recombinant)-rywn)
Rylaze, also known as JZP458, is approved in the U.S. for use as a component of a multi-agent chemotherapeutic regimen for the treatment of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) in adult and pediatric patients one month or older who have developed hypersensitivity to E. coli-derived asparaginase. Rylaze has orphan drug designation for the treatment of ALL/LBL in the United States. Rylaze is a distinct recombinant Erwinia asparaginase that uses a novel Pseudomonas fluorescens expression platform for production. JZP458 was granted Fast Track designation by the U.S. Food and Drug Administration (FDA) in October 2019 for the treatment of this patient population. Rylaze was approved as part of the Real-Time Oncology Review program, an initiative of the FDA’s Oncology Center of Excellence designed for efficient delivery of safe and effective cancer treatments to patients.

The full U.S. Prescribing Information for Rylaze is available at: <View Source>

Important Safety Information

Rylaze should not be given to people who have had:

Serious allergic reactions to Rylaze
Serious swelling of the pancreas (stomach pain), serious blood clots, or serious bleeding during previous asparaginase treatment
Rylaze may cause serious side effects, including:

Allergic reactions (a feeling of tightness in your throat, unusual swelling/redness in your throat and/or tongue, or trouble breathing), some of which may be life-threatening
Swelling of the pancreas (stomach pain)
Blood clots (may have a headache or pain in leg, arm, or chest)
Bleeding
Liver problems
Contact your doctor immediately if any of these side effects occur.

Some of the most common side effects with Rylaze include: liver problems, nausea, bone and muscle pain, infection, tiredness, headache, fever with low white blood cell count, fever, bleeding, mouth swelling (sometimes with sores), pain in the abdomen, decreased appetite, serious allergic reactions, a high blood sugar level, diarrhea, swelling of the pancreas and low levels of potassium in your blood.

Rylaze can harm your unborn baby. Inform your doctor if you are pregnant, planning to become pregnant, or nursing. Females of reproductive potential should use effective contraception (other than oral contraceptives) during treatment and for 3 months following the final dose. Do not breastfeed while receiving Rylaze and for 1 week after the final dose.

Tell your healthcare provider if there are any side effects that are bothersome or that do not go away.

These are not all the possible side effects of Rylaze. For more information, ask your healthcare provider.

Call your doctor for medical advice about any side effects.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088 (1-800-332-1088).

About Acute Lymphoblastic Leukemia
Acute lymphoblastic leukemia (ALL) is a cancer of the blood and bone marrow that can be fast growing.2 Leukemia is the most common cancer in children, and about three out of four of these cases are ALL.3 Although it is one of the most common cancers in children, ALL is among the most curable of the pediatric malignancies due to recent advancements in treatment.4 Adults can also develop ALL, and about four of every 10 cases of ALL diagnosed are in adults.5 The American Cancer Society estimates that about 6,600 new cases of ALL will be diagnosed in the United States in 2022.5

About Lymphoblastic Lymphoma
Lymphoblastic lymphoma (LBL) is a rare, fast-growing, aggressive subtype of non-Hodgkin’s lymphoma (NHL), most often seen in children and teenagers.6 In LBL, the abnormal lymphocytes are present in the lymph nodes or thymus gland, whereas in ALL, the abnormal lymphocytes are mainly in the blood and bone marrow.6

On November 18, 2022 DELBERT Laboratories reported the acquisition from Noventia Pharma Srl of the European MA of CEPLENE 0.5mg/0.5ml, solution for injection (histamine dihydrochloride) on September 12, 2022, and strengthens its commitment in hematology-oncology in Europe (Press release, Laboratoires DELBERT, NOV 18, 2022, View Source [SID1234624251]).

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Ceplene demonstrated a clinical interest in maintenance treatment of acute myeloid leukemia (AML) in patients below 60 years of age in first "complete remission" (symptom-free period of disease after initial treatment) in a clinical study published in Blood in 2006 and received orphan drug designation in 2005 1,2,3.

Acute myeloid leukemias are rare genetic diseases. In Europe, the incidence is estimated at 3.7/100,000 new cases per year. The prognosis for AML is unfavourable with a 5-year relative survival rate of 19%4.

DELBERT Laboratories (View Source) is a French pharmaceutical company specialized in the "renewal of essential medicines" frequently affected by marketing termination, stock shortages, particularly in times of crisis.

"We are focused on keeping essential medicines available to patients in 3 therapeutic areas (Antiinfectives, CNS and Oncology), with the mission of maintaining the therapeutic arsenal of doctors and preventing well-balanced patients from changing treatments.The acquisition of Ceplene’s MA in Europe is part of this strategy to maintain essential medicines and make available medicines with clinical benefit in rare diseases," said Eric Fidelin (Head of Strategy & Global Development).

With this acquisition, DELBERT Laboratories strengthens its presence in hematological oncology.

On November 18, 2022 Eczacıbaşı-Monrol Nuclear Products Co. (Monrol) reported that it has reached an agreement in principal with FutureChem based in Seoul, South Korea, a radiopharmaceutical company, for the clinical supply of radioisotope, Lu-177 n.c.a. (Lutetium-177 non-carrier-added), to support FutureChem’s Investigational New Drug IND-enabling Phase 2 clinical trial with Ludotadipep, 177Lu-FC705 to assess the efficacy and safety for repeated administration of the recommended Ludotadipep dose in patients with metastatic castration resistant prostate cancer (mCRPC) (Press release, Eczacıbaşı-Monrol Nuclear Products, NOV 18, 2022, View Source [SID1234624250]). Clinical supply contract signed by two parties on 18th of Oct 2022 in Barcelona. A new supply contract between Monrol and FutureChem will be signed following the commercialization of the product in South Korea and US.

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Monrol General Manager Aydın Küçük, added: "We are delighted to be working with FutureChem to have a clinical supply agreement to support clinical development program of an innovative radiopharmaceutical product Ludotadipep, 177Lu-FC705 to assess the efficacy and safety in patients with metastatic castration resistant prostate cancer (mCRPC). Collaboration with FutureChem is another example of we continue our mission to improve quality of life for cancer patients and transform patient care for the future."

Dae Yoon Chi, Chief Executive Officer, FutureChem said: "FutureChem is thrilled to be partnering with Monrol, a company with a broad set of offerings to support our development programs and pipeline. We look forward to rolling out the supply of high-quality radioisotopes to our Phase 2a clinical trial patients in US soon. We have a future prospect to expand this partnership, supply of radioisotope, Lu-177 n.c.a. by Monrol for the commercialization of the Ludotadipep, 177Lu-FC705".

On November 18, 2022 Delphinus Medical Technologies reported that it will host demonstrations of the commercially available SoftVue 3D Whole Breast Ultrasound Tomography System (SoftVue) in Booth #2969 in the South Hall of McCormick Place at the annual meeting of the Radiological Society of North America (RSNA) in Chicago Nov. 27 to Dec. 1, 2022 (Press release, Delphinus Medical Technologies, NOV 18, 2022, View Source [SID1234624249]). SoftVue, a 3D whole breast ultrasound tomography system for screening dense breasts, was approved by the U.S. Food & Drug Administration (FDA) in October 2021 and may be paired with a mammography screening at the same visit.

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When paired with the screening mammogram, SoftVue has been shown to identify up to 20 percent more cancers in women with dense breasts while also reducing false positives and decreasing unnecessary call-backs and biopsies.

"SoftVue is a game-changer that will transform clinical practice with a new and highly impactful whole breast ultrasound adjunctive screening modality that will help save lives by identifying cancer sooner for women with dense breasts," said Mark J. Forchette, president and chief executive officer at Delphinus. "We are seeing significant interest and enthusiasm from leading health centers across the country for SoftVue, who see the value of our technology can bring to delivering the best care for patients. To date, SoftVue has been installed at Detroit’s Barbara Ann Karmanos Cancer Institute, and at the East Alabama Medical Center. We are thrilled to be at RSNA this year and look forward to demonstrating SoftVue to radiologists attending the conference."

Also at the RSNA meeting, Dr. Mary Yamashita of the University of Southern California’s Keck School of Medicine will present the results of a study, "Density Awareness: Do Patients Know About Breast Density," showing that a large number of women are not aware of their breast density. Dr. Yamashita’s presentation is scheduled for Nov. 28 at 12:15 p.m. at the McCormick Place exhibition center.

Dense breast tissue (fibrous tissue that can hide cancerous lesions on mammogram) is common, affecting 40 percent of women and making them four times more likely to develop breast cancer. Compounding the increased risk, dense breast tissue, like cancer, typically appears white on a mammogram, making it more challenging to detect cancer early.

SoftVue was developed to address the unmet clinical need for early breast cancer detection in individuals with dense breast tissue and provides a new annual screening solution for this population. The system identifies more cancers, with fewer callbacks, using a proprietary TriAD (Triple Acoustic Detection) technology that effectively characterizes tissue by recording reflection, speed and direction of sound waves moving through breast tissue, unlike traditional ultrasound which utilizes only reflection.

On November 18, 2022 Adaptimmune Therapeutics plc (NASDAQ: ADAP), a leader in cell therapy to treat cancer, reported that clinical and translational data from the final analyses of the pivotal SPEARHEAD-1 trial (Cohort 1) with afamitresgene autoleucel (afami-cel) in patients with advanced synovial sarcoma or myxoid/round cell liposarcoma (MRCLS) at the Connective Tissue Oncology Society (CTOS) annual meeting taking place this week in Vancouver, BC (Press release, Adaptimmune, NOV 18, 2022, View Source [SID1234624248]). The data will be shared in an oral presentation by SPEARHEAD-1 investigator, Brian A. Van Tine, MD, PhD, Washington University School of Medicine in St. Louis, on Friday, November 18th, during Session 9: Immunology & Immunotherapy at 4:39 p.m. UTC/ 7:30 p.m. EST (Paper 61).​

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"With these results, we continue our excitement and optimism about the clear potential of afami-cel to address synovial sarcoma- a difficult-to-treat cancer with high unmet need," said Elliot Norry, Chief Medical Officer, Adaptimmune. "These data reaffirm our commitment to this therapy, and we are very pleased to be able to include these data in our upcoming BLA submission."

Data reinforce clinical efficacy and acceptable safety profile of Adaptimmune’s novel T-cell therapy, afami-cel (August 29, 2022 data cut)

Data continue to support BLA submission for afami-cel in heavily pre-treated patients with synovial sarcoma with an overall response rate of 38.6% by independent review (N=44)
Responses are durable with a median duration of 50 weeks (range: 11.7-122 weeks)
Toxicities include cytokine release syndrome and reversible hematologic toxicities, in line with previous findings indicating an acceptable safety profile
Responses were observed across all evaluated subpopulations​ with higher response rates observed in female patients and those who had higher MAGE-A4 expression, had lower disease burden at baseline, or did not require bridging therapy. Data are consistent with those presented earlier this year as ASCO (Free ASCO Whitepaper)
Translational data indicate that afami-cel drives tumor infiltration of activated and proliferative cytotoxic ("killer") T-cells, shifting the balance from immune-suppressive to a pro-immune in the tumor microenvironment which likely contributes to antitumor response
"We are on the cusp of an exciting and important time for people impacted by synovial sarcoma, a cancer that for much too long has not seen innovative treatment options," said Dr. Brian A. Van Tine, Professor of Medicine and Pediatrics at Washington University School of Medicine in St. Louis. "The SPEARHEAD-1 Trial results provide us a reason to be very optimistic about the game-changing potential to treat more people with this difficult cancer in the very near future."

As previously announced, Cohort 1 of the SPEARHEAD-1 trial has completed treatment and met the primary endpoint for efficacy. Data from Cohort 1 will be used to support Adaptimmune’s BLA submission. Cohort 2 of the SPEARHEAD-1 trial is ongoing with treatment 60% complete and an overall response rate nearly identical to Cohort 1. On September 28th, Adaptimmune received the Vision of Hope Award from the Sarcoma Foundation of America at its Annual Stand Up to Sarcoma Gala.

SPEARHEAD-1 trial design
SPEARHEAD-1 is a Phase 2, open-label trial for people with advanced synovial sarcoma or MRCLS to evaluate the efficacy, safety, and tolerability of afami-cel. Afami-cel SPEAR T-cells target MAGE-A4+ tumors. MAGE-A4 is highly expressed in synovial sarcoma and MRCLS in the context of HLA-A*02. Compelling clinical responses in patients with synovial sarcoma were previously reported with afami-cel in a Phase 1 trial (CTOS 2020). Approximately 90 patients are planned to be treated: 45 in Cohort 1 and 45 in Cohort 2. Enrollment in Cohort 1 is complete, and Cohort 2 is currently recruiting. The primary efficacy analysis will be for Cohort 1 only and will be used to support a BLA filing, which is expected to be initiated in Q4 2022.

No formal hypothesis testing is planned for Cohort 2. Cohort 2 will strengthen the efficacy and safety database and will aid in descriptive sub-group analyses. Key eligibility criteria: ECOG performance status of 0 or 1; HLA*02 positive with MAGE-A4 expression in ≥ 30% of tumor cells ≥ 2+ by immunohistochemistry; aged ≥ 16 and ≤ 75 years; and patients must have received either an anthracycline- or ifosfamide-containing regimen. Eligible patients received afami-cel doses between 1-10 × 109 transduced T-cells after receiving lymphodepleting chemotherapy.