Akebia Therapeutics to Present at Upcoming Investor Conferences

On July 29, 2024 Akebia Therapeutics, Inc. (Nasdaq: AKBA), a biopharmaceutical company with the purpose to better the lives of people impacted by kidney disease, reported participation in two investor conferences in August: BTIG virtual Biotechnology Conference, August 5-6, 2024, and Canaccord Genuity (CG) 44th Annual Growth Conference, August 13-14, 2024 in Boston (Press release, Akebia, JUL 29, 2024, View Source/news-releases/news-release-details/akebia-therapeutics-present-upcoming-investor-conferences-1" target="_blank" title="View Source/news-releases/news-release-details/akebia-therapeutics-present-upcoming-investor-conferences-1" rel="nofollow">View Source [SID1234645139]).

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BTIG Biotechnology Conference
John Butler, Chief Executive Officer, will participate in a fireside chat on Tuesday, August 6, at 8:00 am EST.

CG 44th Annual Growth Conference
Mr. Butler will present on Wednesday, August 14 at 8:30 a.m. EST. A webcast of the presentation can be accessed through the "Investors" section of Akebia’s website at View Source following the conference.

Verastem Oncology Receives FDA Orphan Drug Designation for Avutometinib and Defactinib for the Treatment of Pancreatic Cancer

On July 29, 2024 Verastem Oncology (Nasdaq: VSTM), a biopharmaceutical company committed to advancing new medicines for patients, reported that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to avutometinib, a RAF/MEK clamp, in combination with defactinib, a selective FAK inhibitor, for the treatment of pancreatic cancer (Press release, Verastem, JUL 29, 2024, View Source [SID1234645138]).

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"At the ASCO (Free ASCO Whitepaper) 2024 Annual Meeting, we reported positive initial interim results from the ongoing RAMP 205 trial evaluating avutometinib and defactinib in combination with standard of care chemotherapy in first-line metastatic pancreatic cancer," said Dan Paterson, president and chief executive officer of Verastem Oncology. "The FDA Orphan Drug Designation for the combination of avutometinib and defactinib for the treatment of pancreatic cancer recognizes the substantial unmet treatment need for patients with pancreatic cancer. We believe avutometinib and defactinib in combination with standard of care has an opportunity to provide a different approach in treating this challenging cancer. We look forward to reporting updated data from across dose cohorts in the ongoing RAMP 205 trial in the first quarter of 2025."

At the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in June 2024, Verastem presented initial interim safety and efficacy results from the ongoing RAMP 205 trial of avutometinib and defactinib in combination with current standard of care gemcitabine and nab-paclitaxel in first-line metastatic pancreatic cancer. As of the data cutoff of May 14, 2024, 41 patients had been treated in one of four dose cohort regimens and only patients in dose cohort 1 had a minimum follow up of six months. In the dose level 1 cohort, 83% (5/6) of patients achieved a confirmed partial response with more than six months of follow up at the time of data cutoff. One dose-limiting toxicity (DLT) was observed in the dose level 1 cohort, and the dose level was subsequently cleared after additional patients were enrolled. Of the 26 patients in all cohorts who have had the opportunity to have their first scan while on treatment, 21 have experienced a reduction of the change in target lesion sum of diameters. Read the press release here.

FDA Orphan Drug Designation is granted to certain investigational treatments for diseases or conditions that affect fewer than 200,000 people in the United States. Orphan Drug Designation provides benefits to drug developers, including tax credits for qualified clinical trials, exemptions from certain FDA user fees and the potential for seven years of market exclusivity upon approval.

About Metastatic Pancreatic Cancer

Pancreatic cancer is the third leading cancer in the U.S. and seventh leading cause of cancer-associated mortality worldwide. Metastatic pancreatic cancer is defined as stage IV cancer, where the cancer spreads to other organs. In the U.S., over 30,000 patients are diagnosed with metastatic pancreatic cancer each year, for which the five-year survival rate is 3%. Globally, over 240,000 patients are diagnosed with metastatic pancreatic cancer each year. More than 90% of pancreatic cancers have a KRAS mutation. The standard of care consists of surgery, chemotherapy, radiation or a combination of these approaches.

About RAMP 205 Phase 1/2 Study

RAMP 205 is a multicenter, open-label, single arm Phase 1b/2a study designed to evaluate the safety, tolerability and efficacy of avutometinib and defactinib in combination with standard of care chemotherapy (gemcitabine and Nab-paclitaxel) in patients with previously untreated metastatic pancreatic ductal adenocarcinoma. Part A of the study will evaluate different dose and schedule combinations to determine the recommended Phase 2 dose for expansion into Part B. RAMP 205 is supported by a PanCAN Therapeutic Accelerator Award.

About the Avutometinib and Defactinib Combination

Avutometinib is a RAF/MEK clamp that induces inactive complexes of MEK with ARAF, BRAF and CRAF potentially creating a more complete and durable anti-tumor response through maximal RAS/MAPK pathway inhibition. In contrast to currently available MEK-only inhibitors, avutometinib blocks both MEK kinase activity and the ability of RAF to phosphorylate MEK. This unique mechanism allows avutometinib to block MEK signaling without the compensatory activation of MEK that appears to limit the efficacy of other MEK-only inhibitors. The U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation of the investigational combination of avutometinib and defactinib, a selective FAK inhibitor, for the treatment of all patients with recurrent low-grade serous ovarian cancer (LGSOC) regardless of KRAS status after one or more prior lines of therapy, including platinum-based chemotherapy. Avutometinib alone or in combination with defactinib was also granted Orphan Drug Designation by the FDA for the treatment of LGSOC.

Verastem Oncology is currently conducting clinical trials with avutometinib in RAS/MAPK driven tumors as part of its Raf And Mek Program or RAMP. RAMP 301 (NCT06072781) is an international Phase 3 confirmatory trial evaluating the combination of avutometinib and defactinib versus standard chemotherapy or hormonal therapy for the treatment of recurrent LGSOC. RAMP 201 (NCT04625270) is a Phase 2 registration-directed trial of avutometinib in combination with defactinib in patients with recurrent LGSOC and enrollment has been completed in each of the dose optimization and expansion phases and the low-dose evaluation. Verastem has initiated a rolling NDA submission for avutometinib and defactinib combination in adults with recurrent LGSOC and expects to complete its NDA submission in the second half of 2024 with a potential FDA decision in the first half of 2025.

Verastem Oncology has established clinical collaborations with Amgen and Mirati to evaluate LUMAKRAS (sotorasib) in combination with avutometinib and defactinib and KRAZATI (adagrasib) in combination with avutometinib in KRAS G12C mutant NSCLC as part of the RAMP 203 (NCT05074810) and RAMP 204 (NCT05375994) trials, respectively. The RAMP 205 (NCT05669482), a Phase 1b/2 clinical trial evaluating avutometinib and defactinib with gemcitabine/nab-paclitaxel in patients with front-line metastatic pancreatic cancer, is supported by the PanCAN Therapeutic Accelerator Award.

Syndax Announces PDUFA Action Date Extension for Revumenib NDA for Relapsed or Refractory KMT2Ar Acute Leukemia

On July 29, 2024 Syndax Pharmaceuticals (Nasdaq: SNDX), a clinical stage biopharmaceutical company developing an innovative pipeline of cancer therapies, reported that the U.S. Food and Drug Administration (FDA) has extended the Prescription Drug User Fee Act (PDUFA) action date for the New Drug Application (NDA) for revumenib for the treatment of adults and pediatric patients with relapsed or refractory (R/R) KMT2Ar acute leukemia (Press release, Syndax, JUL 29, 2024, View Source [SID1234645137]).

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The FDA notified Syndax on July 26, 2024 that they required additional time to conduct a full review of supplemental information provided to the FDA in response to their requests. The submission of additional information to the FDA was determined to constitute a Major Amendment to the NDA and resulted in a standard three-month extension to the original PDUFA action date of September 26, 2024. No additional trials or manufacturing information have been requested by the FDA.

"Revumenib, upon approval, will be the first drug indicated to treat patients with KMT2A-rearranged acute leukemia, a population with significant unmet need," said Michael A. Metzger, Chief Executive Officer. "We are confident that the data from the AUGMENT-101 trial, as well as the additional information provided to the FDA, support approval and continue to demonstrate the meaningful benefit revumenib brings to patients with this devastating disease. We look forward to continuing our engagement with the FDA as they complete their review of the NDA by December 26, 2024."

The NDA for revumenib was granted Priority Review and is being reviewed under the FDA’s Real-Time Oncology Review (RTOR) program. The FDA previously granted Breakthrough Therapy, Fast Track and Orphan Drug designations for revumenib.

About Revumenib
Revumenib is a potent, selective, small molecule inhibitor of the menin-KMT2A binding interaction that is being developed for the treatment of KMT2A-rearranged (KMT2Ar), also known as mixed lineage leukemia rearranged or MLLr, acute leukemias including ALL and AML, and mutant nucleophosmin (mNPM1) AML. Positive topline results from the Phase 2 AUGMENT-101 trial in R/R KMT2Ar acute leukemia showing the trial met its primary endpoint were presented at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, and data from the Phase 1 portion of AUGMENT-101 in acute leukemia was published in Nature. Revumenib was granted Orphan Drug Designation for the treatment of AML and ALL by the FDA and for the treatment of AML by the European Commission, and Fast Track designation by the FDA for the treatment of adult and pediatric patients with R/R acute leukemias harboring a KMT2A rearrangement or NPM1 mutation. Revumenib was granted Breakthrough Therapy Designation by the FDA for the treatment of adult and pediatric patients with R/R acute leukemia harboring a KMT2A rearrangement.

About the Real-Time Oncology Review Program (RTOR)

RTOR provides a more efficient review process for oncology drugs to ensure that safe and effective treatments are available to patients as early as possible, while improving review quality and engaging in early iterative communication with the applicant. Specifically, it allows for close engagement between the sponsor and the FDA throughout the submission process and it enables the FDA to review individual sections of modules of a drug application rather than requiring the submission of complete modules or a complete application prior to initiating review. Additional information about RTOR can be found at: View Source

Haystack Oncology and Université de Montréal’s affiliated hospital research centre, the CRCHUM, to Deploy Haystack MRD™ Technology in Research Study for Metastatic Colorectal Cancer

On July 29, 2024 Haystack Oncology, a Quest Diagnostics (NYSE: DGX) company, reported a research collaboration with Dr. Simon Turcotte, hepatopancreatobiliary surgeon and scientist at Université de Montréal’s affiliated hospital research centre, the CRCHUM, to utilize Haystack Oncology’s personalized MRD technology (Haystack MRD) to evaluate treatment effectiveness in patients with metastatic colorectal cancer (mCRC) with metastases confined to the liver (Press release, Quest Diagnostics, JUL 29, 2024, View Source,-the-CRCHUM,-to-Deploy-Haystack-MRD-TM-Technology-in-Research-Study-for-Metastatic-Colorectal-Cancer [SID1234645136]).

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This prospective, observational study, Early Detection of Treatment Failure in Metastatic Colorectal Cancer Patients (eDetect), will use Haystack MRD to assess circulating tumor DNA (ctDNA) as an early biological marker of treatment response and disease recurrence in patients with mCRC undergoing systemic treatment and liver surgery with curative intent. Haystack MRD is a blood-based liquid biopsy test that measures ctDNA shed into circulation by solid tumors in order to identify residual, recurrent, or resistant cancer, at the earliest possible stage.

"Our collaboration with the CRCHUM presents a valuable opportunity to leverage the performance of our Haystack MRD technology in a population of mCRC patients for whom cure is possible," said Dan Edelstein, Vice President and General Manager of Haystack Oncology. "Designed for detecting ctDNA with exceptional sensitivity, Haystack MRD is well-suited to measure treatment response in oligometastatic CRC patients to better understand how ctDNA can guide the sequence and intensity of therapy in the future."

Université de Montréal’s affiliated hospital research centre, the CRCHUM, is one of North America’s leading hospital research centres. Located in the heart of Montreal, the CRCHUM is a major centre for creation, knowledge generation and training.

"mCRC is a challenging disease in need of improved biomarkers to guide optimal patient care," said Dr. Simon Turcotte, hepatopancreatobiliary surgeon and scientist at the CRCHUM, also principal investigator of the eDetect study. "By teaming up with Haystack, we will be able to understand the best use of the MRD technology to inform treatment decisions. This will guide the design of future interventional trials to assess impact on patient survival."

Colorectal cancer is the second leading cause of cancer death in Canada and the United States, representing approximately 62,310 related deaths in 2023.1,2 While early-stage CRC can frequently be cured by surgery (with or without adjuvant chemotherapy), mCRC is often treatment-resistant and can be more difficult to address.3

Metastases are the primary cause of colorectal cancer-related mortality, with the liver being the most frequent site for metastasis, followed by the lung. Patients presenting with metastases confined to the liver represent a unique clinical opportunity to pursue surgery with intent to cure. However, even after surgery with no evidence of residual tumor by medical imaging, 80% of patients relapse. A more sensitive diagnostic tool, such as ctDNA, is needed to detect whether residual microscopic cancer cells remain after surgery, to detect relapse earlier than medical imaging so as to treat before the disease burden is too high, and to know as early as possible whether chemotherapy is effective to limit unnecessary use and side effects.

Novartis Scemblix® granted FDA Priority Review for the treatment of adults with newly diagnosed CML 

On July 29, 2024 Novartis reported that Scemblix (asciminib) has been granted Priority Review status by the US Food and Drug Administration (FDA) for treatment of newly diagnosed adult patients with Philadelphia chromosome-positive CML in chronic phase (Ph+ CML-CP) (Press release, Novartis, JUL 29, 2024, View Source [SID1234645135]).

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The FDA grants Priority Review to medicines that address serious or life-threatening diseases or conditions and, if approved, would provide significant improvements in treatment safety or efficacy5. Scemblix previously received Breakthrough Therapy designation for the treatment of newly diagnosed adult patients and is currently being reviewed under the FDA’s Real-Time Oncology Review (RTOR) program. Scemblix received Priority Review and Breakthrough Therapy designations at the time of the original new drug application for the treatment of adult patients with Ph+ CML-CP who have previously been treated with two or more TKIs2-4,6,7.

"We welcome the FDA’s decision to grant Priority Review and Breakthrough Therapy designations to Scemblix for newly diagnosed CML patients, which underscores the substantial need for additional effective, safe and tolerable treatment options," said Rodney Gillespie, Senior Vice President, Therapeutic Area Head, US Oncology, Novartis. "The ASC4FIRST data indicate that Scemblix, if approved, has the potential to address a critical gap in CML by offering a highly effective treatment along with a favorable safety and tolerability profile."

Priority Review designation is based on results from ASC4FIRST, a Phase III study that evaluated the efficacy, tolerability and safety of once daily Scemblix against investigator-selected (IS) tyrosine kinase inhibitors (TKIs) (imatinib, nilotinib, dasatinib, and bosutinib) representing the current standard of care (SoC) in newly diagnosed adult patients with Ph+ CML-CP1. Scemblix demonstrated superior major molecular response (MMR) rates in both primary endpoints at week 48 vs. IS SoC TKIs (68% vs. 49.0%) and imatinib alone (69% vs. 40%)1. Additionally, Scemblix is the first CML treatment to show superior efficacy along with a favorable safety and tolerability profile vs. imatinib and 2G TKIs, with fewer grade ≥3 AEs (38% vs. 44% and 55%), dose adjustments (30% vs. 39% and 53%) and half the rate of AEs leading to treatment discontinuation (5% vs. 11% and 10%)1. In newly diagnosed patients, the safety profile was consistent with previous registration studies, with no new safety concerns observed1.

Earlier this year, ASC4FIRST data were presented as a late-breaking abstract at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, as a plenary at the European Hematology Association (EHA) (Free EHA Whitepaper) 2024 Congress and published in The New England Journal of Medicine1.

Scemblix is currently approved by the FDA, European Medicines Agency and other regulatory authorities for adult patients with Ph+ CML-CP who have been treated previously with two or more TKIs2,4,6.

About ASC4FIRST Phase III Clinical Trial
ASC4FIRST (NCT04971226) is a Phase III, head-to-head, multi-center, open-label, randomized study of oral Scemblix 80 mg QD vs. investigator-selected first- or second-generation TKIs (imatinib, nilotinib, dasatinib or bosutinib) in 405 adult patients with newly diagnosed Ph+ CML-CP6. The two primary endpoints of the study are to compare efficacy of asciminib vs. investigator-selected SoC TKIs and to compare efficacy vs. that of TKI within the stratum of participants with imatinib as pre-randomization selected TKI, based on proportion of patients that achieve MMR at week 486.

The study remains ongoing with key secondary endpoints of proportion of patients that achieve MMR at week 96 and a safety endpoint of discontinuation of study treatment due to an AE (TTDAE) by week 966. The study also assesses additional secondary safety and efficacy endpoints, including MMR, MR4, MR4.5, complete hematological response (CHR) and BCR::ABL1 ≤1% at and by all scheduled data collection time points; duration of and time to first MMR, MR4 and MR4.5; time to treatment failure; event-free survival, failure-free survival, progression-free survival and overall survival6.

About Scemblix (asciminib)
Scemblix is the first CML treatment that works by Specifically Targeting the ABL Myristoyl Pocket (referred to as a STAMP inhibitor in scientific literature)8-10. The current approved CML treatments are TKIs that target the ATP-binding site (ATP-competitive)10.

Scemblix is approved in more than 70 countries, including the US, the EU and JP, to treat adults with Ph+ CML-CP who have previously been treated with two or more TKIs2,3,7. In some countries, including the US, Scemblix is also approved in patients with Ph+ CML-CP with the T315I mutation2-4.

Scemblix is an important treatment option for patients who experience resistance and/or intolerance after two prior TKI therapies11-26, and it is being studied across multiple treatment lines for Ph+ CML-CP, both as a monotherapy and in combination6,8,9,19,27-39.

About Novartis Commitment to CML
Novartis has a long-standing scientific commitment to patients living with CML. For more than two decades, our bold science has helped transform CML from a life-limiting to a chronic condition for many patients. Despite these advancements, there’s still work to be done. We continue to research ways to target the disease more selectively and to address the challenges of not reaching treatment efficacy goals, experiencing treatment resistance and/or intolerance that many patients face. Our legacy inspires our future innovation – we continue to lead the way in developing novel medicines to address serious unmet needs in CML. Our commitment also goes beyond science. Our 20+ year collaboration with the Max Foundation has provided access to Gleevec (imatinib), Tasigna (nilotinib) and now Scemblix and is delivering tremendous patient impact in low- and middle-income countries, with over 100,000 patients supported to date.

Indication
SCEMBLIX (asciminib) tablets is a prescription medicine used to treat adults with Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP), previously treated with 2 or more tyrosine kinase inhibitor (TKI) medicines.
SCEMBLIX is also approved for use in adults with Ph+ CML in CP with the T315I mutation.

It is not known if SCEMBLIX is safe and effective in children.

Important Safety Information
SCEMBLIX (asciminib) tablets may cause low platelet counts (thrombocytopenia), low white blood cell counts (neutropenia), and low red blood cell counts (anemia). Patients should tell their doctor right away if they have unexpected bleeding or easy bruising; blood in their urine or stools; fever; or any signs of an infection. SCEMBLIX may increase enzymes in the patient’s blood called amylase and lipase, which may be a sign of inflammation of the pancreas (pancreatitis). Patients should tell their doctor right away if they have sudden stomach-area pain or discomfort, nausea, or vomiting. During treatment with SCEMBLIX, doctors may check their patients’ blood pressure and treat any high blood pressure as needed. Patients should tell their doctor if they develop elevated blood pressure or symptoms of high blood pressure including confusion, headaches, dizziness, chest pain, or shortness of breath.

If a patient has an allergic reaction while on SCEMBLIX, they should stop taking SCEMBLIX and get medical help right away. Signs or symptoms of an allergic reaction include trouble breathing or swallowing; feeling dizzy or faint; swelling of the face, lips, or tongue; fever; skin rash or flushing; or a fast heartbeat. SCEMBLIX may cause heart and blood vessel problems, including heart attack; stroke; blood clots or blockage of patient’s arteries; heart failure; and abnormal heartbeat which can be serious and may sometimes lead to death. These heart and blood vessel problems can happen in people with risk factors or a history of these problems and/or previously treated with multiple TKI medicines. Patients should tell their doctor right away if they get shortness of breath; chest pain or pressure; a feeling like their heart is beating too fast or they feel abnormal heartbeats; swelling in their ankles or feet; dizziness; weight gain; numbness or weakness on one side of their body; decreased vision or loss of vision; trouble talking; pain in their arms, legs, back, neck, or jaw; headache; or severe stomach-area pain.

Before taking SCEMBLIX, patients should tell their doctor about all of their medical conditions, including if they have a history of pancreatitis; a history of heart problems; or blood clots in their arteries and veins (types of blood vessels). SCEMBLIX can harm an unborn baby. Women should tell their doctor right away if they become pregnant or think they may be pregnant during treatment with SCEMBLIX. Women who are able to become pregnant should have a pregnancy test before they start SCEMBLIX and should use effective birth control during treatment and for 1 week after the last dose of SCEMBLIX. Women should not breastfeed during treatment and for 1 week after their last dose of SCEMBLIX.

Patients should tell their doctor about all the medicines they take, including prescription medicines, over-the-counter medicines, vitamins, and herbal supplements. SCEMBLIX and other medicines may affect each other, causing side effects. The most common side effects of SCEMBLIX include nose, throat, or sinus (upper respiratory tract) infections; muscle, bone, or joint pain; rash; tiredness; nausea; and diarrhea. The most common blood test abnormalities include decreased blood counts of platelets, white blood cells, and red blood cells; and increased blood levels of triglycerides, creatine kinase, liver enzymes, or pancreas enzymes (amylase and lipase).

Please see full Prescribing Information for SCEMBLIX, available at View Source