On February 11, 2025 Specialised therapeutics reported that a new breast cancer therapy shown to significantly reduce the risk of cancer recurrence and improve disease-free survival in women is now approved for use in Thailand (Press release, Specialised Therapeutics Asia, FEB 11, 2025, View Source [SID1234650180]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

NERLYNX (neratinib), an oral medication, has been approved by the Thailand Food and Drug Administration (Thailand FDA) as a single agent "for the extended adjuvant treatment of adult patients with early-stage hormone receptor positive HER2-overexpressed/amplified breast cancer and who completed adjuvant trastuzumab-based therapy less than one year ago."[1] Additionally, NERLYNX has been approved in combination with capecitabine"for the treatment of adult patients with advanced or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 based regimens in the metastatic setting."

In early breast cancer, NERLYNX has been shown to significantly reduce the ongoing risk of recurrence in women positive for human epidermal growth factor receptor 2 (HER2+), with the greatest benefit seen in women who are also hormone-receptor positive (HR+) and who commence therapy within 12 months of completing trastuzumab-based therapy.[2,3] For these women, the five-year risk of recurrence is reduced by up to 42%.

In women with advanced or metastatic HER2+ breast cancer, NERLYNX in combination with capecitabine (N+C) was found to significantly improve mean progression free survival (PFS) by 2.2 months over treatment with lapatinib plus capecitabine (L+C).[5] The duration of treatment response was longer for patients administered N+C (8.5 months) versus L+C (5.6 months), while the risk of disease progression or death was reduced by up to 24% among those treated with N+C at a median follow-up of 30 months.

NERLYNX is being made available in Thailand by independent pharmaceutical company, Specialised Therapeutics (ST), under exclusive license from Puma Biotechnology, Inc.

ST Chief Executive Officer, Mr Carlo Montagner, said the approval of NERLYNX in Thailand was an important milestone for the company.

"We are proud to have obtained approval of NERLYNX in Thailand for adults with HER2 positive breast cancer. This is a significant milestone for Specialised Therapeutics, but importantly also for women diagnosed with breast cancer in Thailand who will be presented with an opportunity to access a treatment that will help reduce the risk of disease recurrence and improve outcomes, in either the early or advanced stages of their disease."

Breast cancer is the most common cancer diagnosed in Thai women, and the second leading cause of cancer mortality in females, behind liver cancer.[7] The incidence of breast cancer in Thailand has been rising at an alarming rate, with the annual age-standardised incidence rate doubling over the past 20 years (from 17.8/100,000 in 1998, to 35.7/100,000 in 2020).[8,9] In 2022, 21,628 Thai women were newly diagnosed with breast cancer, accounting for almost a quarter (23.2%) of all new cancer diagnoses in females.[7]

Coinciding with the NERLYNX approval, ST is also pleased to announce the growth of its Thailand office, with new field force members due to join the company in March 2025.

"We are extremely excited about the new journey we are undertaking in Thailand," said Mr Montagner. "Hiring our first field force employees, who have an extensive understanding of the local healthcare landscape, enables us to connect with oncologists around the country at the earliest opportunity, ahead of launching NERLYNX and making it available for eligible breast cancer patients as soon as possible.

"As we continue to seek approvals for our strong pipeline of specialised medicines and technologies, we remain committed to meeting the needs of patients with rare diseases across Thailand, and making a difference to their lives. We look forward to working with the Thailand FDA and local specialists as we endeavour to provide timely access to these new treatments for the patients that need them."

About NERLYNX

NERLYNX (neratinib) is an irreversible tyrosine kinase inhibitor (TKI) that blocks signal transduction through the epidermal growth factor receptors, HER1, HER2 and HER4.[10] It is an oral tablet and works by binding to multiple receptors inside the cancer cell, blocking signals that tell cancer cells to grow and multiply.[11,12]

NERLYNX has received approval for the treatment of certain patients with extended adjuvant and/or metastatic HER2-positive breast cancer in more than 40 countries outside the United States (US), including the European Union (EU), China, Latin America, Australia, Canada, and Hong Kong.

About HER2-Positive (HER2+) Breast Cancer

Approximately 20-25% of breast cancer tumours over-express the HER2 protein. HER2-positive (HER2+) breast cancer is a highly heterogeneous tumour that is often more aggressive than other types of breast cancer and has a poor prognosis, increasing the risk of disease progression and death.[10,13,14]

While trastuzumab has helped to improve the survival and prognosis of patients with HER2+ breast cancer, around 20-30% of patients will experience recurrence and metastases after trastuzumab targeted therapy.[14]

About the ExteNET Study

The ExteNET trial was a double-blind, placebo-controlled, Phase III trial of neratinib versus placebo after adjuvant treatment with trastuzumab (Herceptin) in patients with early-stage HER2-positive breast cancer.

The ExteNET trial randomised 2,840 patients in 41 countries with early-stage HER2-positive breast cancer who had undergone surgery and adjuvant treatment with trastuzumab. After completion of adjuvant treatment with trastuzumab, patients were randomised to receive neratinib or placebo for a period of one year. Patients were then followed for recurrent disease, ductal carcinoma in situ (DCIS), or death for a period of five years after randomisation.

The primary endpoint of the trial was invasive disease-free survival (iDFS). The trial demonstrated that after a median follow up of 5.2 years, treatment with neratinib resulted in a 27% reduction of risk of invasive disease recurrence or death versus placebo (hazard ratio = 0.73, p = 0.008). The 5-year iDFS rate for the neratinib arm was 90.2%, versus 87.7% for the placebo arm. An additional five-year sub-group analysis demonstrated a 42% reduction in risk of recurrence and 59% reduction in risk of CNS recurrence or death of any cause in women who were HR+ and who had commenced neratinib therapy within 12 months of completing treatment with trastuzumab.

The most common adverse reactions (≥ 5%) were diarrhoea, nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite, muscle spasms, dyspepsia, AST or ALT increase, nail disorder, dry skin, abdominal distention, epistaxis, weight decreased and urinary tract infection.

About the NALA Study

The NALA trial was a randomised, active-controlled, Phase III trial investigating the efficacy of neratinib, an irreversible pan-HER tyrosine kinase inhibitor (TKI), plus capecitabine (N+C) against lapatinib, a reversible dual TKI, plus capecitabine (L+C) in patients with centrally confirmed HER2+ metastatic breast cancer who had received two or more prior anti-HER2 based regimens in the metastatic setting. 621 patients were enrolled at 203 sites in 28 countries across Europe, North and South America, Asia, and Australia.

The primary outcome measures for the trial were progression-free survival (PFS), and overall survival (OS). Median PFS was 5.6 months for patients who received N+C and 5.5 months for those receiving L+C (hazard ratio = 0.76, p = 0.0059). The PFS rate at 12 months was 29% versus 15%, respectively. Median OS was 21 months for patients receiving N+C, compared to 18.7 months for those receiving L+C (hazard ratio = 0.88, p = 0.2086).

The most common adverse reactions of any grade (>5%) in the N+C arm were diarrhoea, nausea, vomiting, decreased appetite, constipation, fatigue/asthenia, decreased weight, dizziness, back pain, arthralgia, urinary tract infection, upper respiratory tract infection, abdominal distention, renal impairment, and muscle spasms.

On February 11, 2025 Tyra Biosciences, Inc. (Nasdaq: TYRA), a clinical-stage biotechnology company focused on developing next-generation precision medicines that target large opportunities in Fibroblast Growth Factor Receptor (FGFR) biology, reported that company management will participate in the following investor conferences (Press release, Tyra Biosciences, FEB 11, 2025, View Source [SID1234650179]):

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Oppenheimer 35th Annual Healthcare Life Sciences Conference, February 11-12, 2025
Format: Fireside chat and one-on-one investor meetings
Presentation Date/Time: Wednesday, February 12, 2025, at 2:00 PM ET
Location: Virtual
TD Cowen 45th Annual Healthcare Conference, March 3-5, 2025
Format: Fireside chat and one-on-one investor meetings
Presentation Date/Time: Monday, March 3, 2025, at 9:50 AM ET
Location: Boston
Jefferies Biotech on the Beach Summit, March 11-12, 2025
Format: One-on-one investor meetings
Location: Miami
Barclays 27th Annual Global Healthcare Conference, March 11-13, 2025
Format: Fireside chat and one-on-one investor meetings
Presentation Date/Time: Wednesday, March 12, 2025, at 8:30 AM ET
Location: Miami

A live and archived webcast of the fireside chats will be available via the For Investors page on the Investor section of the TYRA website.

On February 11, 2025 Veracyte, Inc. (Nasdaq: VCYT), a leading cancer diagnostics company, reported that 17 Decipher-focused abstracts will be presented at the 2025 ASCO (Free ASCO Whitepaper) Genitourinary Cancers Symposium (ASCO GU) (Press release, Veracyte, FEB 11, 2025, View Source [SID1234650178]). The findings demonstrate the market leadership of its Decipher tests in better informing treatment decisions for patients with prostate and bladder cancers, compared to standard approaches, and in helping to drive innovation that will inform the future of urologic cancer care. The conference will take place February 13-15 in San Francisco.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The scale and scope of data to be presented at the ASCO (Free ASCO Whitepaper) GU meeting underscore the impact our whole-transcriptome-based Decipher tests are having in treating patients with urologic cancers, and how our GRID, or Genomic Resource for Intelligent Discovery, research tool is helping to advance scientific understanding of these diseases," said Elai Davicioni, Ph.D., Veracyte’s medical director, Urology. "Our commitment to generating robust clinical evidence with collaborators has led to our market-leading Decipher Prostate test achieving the highest status among gene expression tests in the most recent, and prior, NCCN guidelines.* We look forward to using a similar approach for our Decipher Bladder test in bladder cancer."

"Clinical rigor and robust evidence generation are important for a molecular test to gain widespread adoption and inclusion in guidelines for helping physicians and their patients with prostate cancer make better-informed treatment decisions," said Daniel Spratt, M.D., of the University Hospitals Seidman Cancer Center, Case Western Reserve University. "National guidelines have acknowledged the large body of work from randomized Phase 3 trials that have been profiled with Decipher and include the Decipher test as an advanced risk-stratification tool that can aid in shared-decision making for patients."

Key Decipher-focused findings to be presented at the ASCO (Free ASCO Whitepaper) GU Symposium are:

Title:

Decipher Score as a Predictor of Response to Treatment Intensification in the NRG Oncology-RTOG 0534 (SPPORT) Phase III Randomized Post-Prostatectomy Salvage Radiotherapy Trial

Presenter:

Alan Pollack, M.D., Ph.D., University of Miami Health System

Format:

Poster (#K29)

Abstract #:

399

Date/Time:

Thursday, February 13, 2025; 11:25 a.m.—12:45 p.m. PST

Location:

Level 1, West Hall; On Demand

Summary:

A post-hoc analysis of the NRG Oncology/RTOG 05-34 (SSPORT) Phase 3, randomized trial shows that the Decipher Prostate test may inform treatment intensification strategies in patients undergoing salvage radiotherapy by identifying those who will benefit from pelvic nodal radiation.

Title:

A non-coding RNA based classifier for favorable outcomes in clinically organ confined bladder cancer

Presenter:

Yair Lotan, M.D., UT Southwestern Medical Center

Format:

Poster (#G27)

Abstract #:

831

Date/Time:

Friday, February 14, 2025; 11:30 a.m.—12:45 p.m. PST

Location:

Level 1, West Hall; On Demand

Summary:

Study findings show that the Decipher Bladder test accurately identifies patients whose bladder cancer has a luminal molecular subtype, which is associated with favorable outcomes. Such findings could help clinicians determine which patients are less likely to benefit from intensified therapy.

Title:

Gene signature predictor of dose-response to prostate radiation: validation of PORTOS in phase III trials

Presenter:

Shuang Zhao, M.D., University of Wisconsin-Madison

Format:

Oral Presentation

Abstract #:

308

Date/Time:

Thursday, February 13, 2025; 8:00 a.m.—9:40 a.m. PST

Location:

Level 3, Ballroom; Live Stream

Summary:

Analyses of two prospective, randomized, Phase 3 trials (RTOG 01-26 and SAKK 09/10) show that the PORTOS gene expression signature – currently part of the Decipher GRID research tool – predicts which patients will benefit from dose-escalated radiation therapy in both primary and salvage treatment settings.

Additional notable Decipher-focused presentations include:

Title:

Decipher Risk Stratification of Radiorecurrent Prostate Cancer: Correlative Analysis of the F-SHARP Trial of Salvage Reirradiation

Presenter:

Abhishek Solanki, M.D., M.S., Loyola University Chicago

Format:

Poster (#L15)

Abstract #:

419

Date/Time:

Thursday, February 13, 2025; 11:25 a.m.—12:45 p.m. PST

Location:

Level 1, West Hall; On Demand

Summary:

Radiation therapy is increasingly used for patients whose prostate cancer has recurred following initial radiation treatment. This study suggests the Decipher Prostate test can identify patients who are likely to benefit from more radiation alone versus those who may also need further treatment intensification.

Title:

Androgen receptor activity in biopsy specimens at initial diagnosis of prostate cancer and correlation with outcomes and treatment response

Presenter:

Nicole Handa, M.D., Northwestern University, Feinberg School of Medicine

Format:

Poster (#L5)

Abstract #:

409

Date/Time:

Thursday, February 13, 2025; 11:25 a.m.—12:45 p.m. PST

Location:

Level 1, West Hall; On Demand

Summary:

Using the Decipher GRID research tool to assess transcriptome-wide expression data and clinical factors, investigators found that low androgen receptor activity (AR-A) was associated with poor outcomes for prostate cancer patients. They suggest such patients could potentially benefit from post-operative radiation therapy and PARP inhibitors.

Title:

Risk Stratification Using the Decipher 22-gene Genomic Classifier (GC) and Digital Pathology Artificial Intelligence (DPAI) in Nearly 10,000 Localized Prostate Cancer Patients

Presenter:

Daniel Spratt, M.D., University Hospitals Seidman Cancer Center, Case Western Reserve University

Format:

Poster (#L4)

Abstract #:

408

Date/Time:

Thursday, February 13, 2025; 11:25 a.m.—12:45 p.m. PST

Location:

Level 1, West Hall; On Demand

Summary:

This large study found that adding digital pathology artificial intelligence (DPAI) tools to the Decipher Prostate Genomic Classifier did not further improve the molecular test’s prognostic performance. Ongoing research is underway to explore whether there may be specific clinical states where the combination of DPAI and the Decipher test may add meaningful clinical utility.

"The extensive Decipher-focused data at the 2025 ASCO (Free ASCO Whitepaper) GU Symposium demonstrate the power of our novel Veracyte Diagnostics Platform, which begins with delivering high-performing tests using a comprehensive, whole-transcriptome approach. This enables additional research, which in turn supports further innovation to help more patients," said Phillip Febbo, M.D., Veracyte’s chief scientific officer and chief medical officer.

Veracyte’s Decipher team will be at Booth #37 at the 2025 ASCO (Free ASCO Whitepaper) GU Symposium. More information, including a full list of Decipher-focused abstracts being presented, can be found here.

About Decipher Prostate

The Decipher Prostate Genomic Classifier is a 22-gene test, developed using RNA whole-transcriptome analysis and machine learning, that helps inform treatment decisions for patients with prostate cancer. The test is performed on biopsy or surgically resected samples and provides an accurate risk of developing metastasis with standard treatment. Armed with this information, physicians can better personalize their patients’ care and may recommend less-intensive options for those at lower risk or earlier, more-intensive treatment for those at higher risk of metastasis. The Decipher Prostate test has been validated in many dozens of published studies involving more than 100,000 patients. It is the only gene expression test to achieve "Level 1B" evidence status and inclusion in the risk-stratification table in the most recent NCCN Guidelines* for prostate cancer. More information about the Decipher Prostate test can be found here.

About Decipher Bladder

The Decipher Bladder Genomic Classifier is a 219-gene test, developed using RNA whole-transcriptome analysis and machine learning, that is designed for use in patients following bladder cancer diagnosis who face questions regarding treatment intensity. The test classifies bladder tumors into five molecular subtypes, each having distinct tumor biology and potential clinical implications. This information can help physicians and their patients better understand the degree of benefit that would likely be gained from neoadjuvant chemotherapy and/or the likelihood of harboring non-organ-confined disease at time of surgery, respectively. More information about the Decipher Bladder test can be found here.

About Decipher GRID

The Decipher GRID database includes more than 200,000 whole-transcriptome profiles from patients with urologic cancers and is used by Veracyte and its partners to contribute to continued research and help advance understanding of prostate and other urologic cancers. GRID-derived information is available on a Research Use Only basis. More information about Decipher GRID can be found here.

On February 11, 2025 SpringWorks Therapeutics, Inc. (Nasdaq: SWTX), a commercial-stage biopharmaceutical company focused on severe rare diseases and cancer, reported that the U.S. Food and Drug Administration (FDA) has approved GOMEKLI (mirdametinib), SpringWorks’ MEK inhibitor, for the treatment of adult and pediatric patients 2 years of age and older with neurofibromatosis type 1 (NF1) who have symptomatic plexiform neurofibromas (PN) not amenable to complete resection (Press release, SpringWorks Therapeutics, FEB 11, 2025, View Source [SID1234650177]). With the approval, SpringWorks was granted a rare pediatric disease priority review voucher (PRV) by the FDA.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The NF1-PN patient community has a great need for more treatment options. With today’s approval, we are honored to serve both adults and children with NF1-PN and provide them with a therapy that has the potential to shrink their tumors and offer meaningful symptomatic relief," said Saqib Islam, Chief Executive Officer of SpringWorks. "We are grateful to each clinical trial participant, their families, the investigators, and the patient advocacy groups involved in the journey towards making GOMEKLI available in the U.S. I am proud that we are delivering on our commitment to patients with devastating diseases with our company’s second FDA approval in less than 18 months."

NF1 is a genetic disorder that currently affects approximately 100,000 children and adults in the United States.2,3 Patients with NF1 have approximately a 30-50% lifetime risk of developing plexiform neurofibromas, or PNs, which are tumors that grow in an infiltrative pattern along the peripheral nerve sheath and that can cause severe disfigurement, pain and functional impairment.2,4 There are approximately 40,000 people in the United States living with NF1-PN, the majority of whom are adults that have not had an approved medicine until GOMEKLI.5 Plexiform neurofibromas can transform into malignant peripheral nerve sheath tumors, an aggressive and potentially fatal disease.6 Surgical removal can be challenging due to the infiltrative tumor growth pattern of plexiform neurofibromas along nerves, and up to approximately 85% of plexiform neurofibromas are considered not amenable to complete resection.7,8,9

"Patients with NF1-PN often face significant challenges with their health and have had limited treatment options to manage this devastating condition," said Christopher Moertel, M.D., Medical Director Pediatric Neuro-Oncology and Neurofibromatosis Programs and Kenneth and Betty Jayne Dahlberg Professor of Pediatrics, University of Minnesota, and lead investigator of the ReNeu trial. "It was very encouraging in the ReNeu trial to see that GOMEKLI provided deep and durable responses, with a manageable safety profile that enabled patients to stay on therapy. This approval represents an important advance, especially for adults who previously did not have an approved treatment."

GOMEKLI was approved under Priority Review and SpringWorks received a rare pediatric disease priority review voucher from the FDA. GOMEKLI was previously granted Orphan Drug and Fast Track designations for the treatment of NF1-PN.

The FDA approval of GOMEKLI is based on results from the Phase 2b ReNeu trial, which enrolled 114 patients with NF1-PN ≥2 years of age (58 adults and 56 pediatric patients).10 GOMEKLI met the primary endpoint of confirmed objective response rate (ORR), as assessed by blinded independent central review, demonstrating a 41% ORR (N= 24/ 58) in adults and 52% in children (N=29/56).10 Tumor volume reductions were deep and durable; the median best percentage change in target PN volume was -41% (range: -90 to 13%) in adults and -42% (range: -91 to 48%) in children.10 Eighty-eight percent of adults and 90% of children with a confirmed response had a response of at least 12 months duration, and 50% and 48%, respectively, had a response of at least 24 months duration.10 Patients in both cohorts also experienced early and sustained significant improvements from baseline in pain, and quality of life, as assessed across multiple patient-reported outcome tools.10

GOMEKLI demonstrated a manageable safety and tolerability profile.1 The most common adverse events (>25%) reported in adults receiving GOMEKLI were rash, diarrhea, nausea, musculoskeletal pain, vomiting and fatigue.1 The most common adverse events (>25%) occurring in children were rash, diarrhea, musculoskeletal pain, abdominal pain, vomiting, headache, paronychia, left ventricular dysfunction, and nausea.1 Please see additional Important Safety Information below, including Warnings & Precautions relating to ocular toxicity, left ventricular dysfunction, dermatologic adverse reactions, and embryo-fetal toxicity.

"We are excited to celebrate the extraordinary milestone of our partners and long-term friends at SpringWorks for the NF1-PN community. This FDA approval shows the power of collaboration to advance innovative science for drugs that may otherwise not have been taken forward," said Annette Bakker, Ph.D., Chief Executive Officer of the Children’s Tumor Foundation. "When industry, researchers, and organizations like ours driving treatment innovation join forces, scientific progress moves faster, and patients gain access to the therapies they need. Every treatment approval is hard-won, built on research, persistence, and partnership. Today, that work delivers a critical new option for NF patients of all ages."

"NF1-PN is a complex, devastating disease that affects not only individual patients, but entire families. Treatment advances are crucial to achieving better outcomes for patients and this FDA approval offers hope for NF patients and their families," said Kim Bischoff, Executive Director, NF Network.

SpringWorks is dedicated to helping patients with NF1-PN access GOMEKLI and to providing support throughout their treatment journey. The SpringWorks CareConnections program is a comprehensive patient support program that offers personalized support services and resources to eligible GOMEKLI patients, including insurance coverage information and access support, financial assistance and personalized educational and emotional support. Physicians and patients can contact 1-844-CARES-55 (1-844-227-3755) or visit www.springworkstxcares.com for more information.

GOMEKLI is available in 1 and 2 mg capsules and in a 1mg tablet for oral suspension, which dissolves easily in water. GOMEKLI is expected to be available through a specialty pharmacy and specialty distributor network in the United States within two weeks.

SpringWorks’ Marketing Authorization Application for mirdametinib for the treatment of children and adults with NF1-PN was validated by the European Medicines Agency (EMA) and is currently under review; a decision is expected from the European Commission in 2025.

About NF1-PN

Neurofibromatosis type 1 (NF1) is a rare genetic disorder that arises from mutations in the NF1 gene, which encodes for neurofibromin, a key suppressor of the MAPK pathway.11,12 NF1 is the most common form of neurofibromatosis, with an estimated global birth incidence of approximately 1 in 2,500 individuals, and there are approximately 100,000 patients living with NF1 in the United States.2,3 The clinical course of NF1 is heterogeneous and manifests in a variety of symptoms across numerous organ systems, including abnormal pigmentation, skeletal deformities, tumor growth and neurological complications, such as cognitive impairment.13 Patients with NF1 have an 8 to 15-year mean reduction in their life expectancy compared to the general population.14

NF1 patients have approximately a 30-50% lifetime risk of developing plexiform neurofibromas, or PN, which are tumors that grow in an infiltrative pattern along the peripheral nerve sheath and that can cause severe disfigurement, pain and functional impairment; in rare cases, NF1-PN may be fatal.2,4,6 NF1-PNs are most often diagnosed in the first two decades of life.2 These tumors can be aggressive and are associated with clinically significant morbidities; typically, they grow more rapidly during childhood.15,16

Surgical removal of these tumors can be challenging due to the infiltrative tumor growth pattern along nerves and can lead to permanent nerve damage and disfigurement.6 Up to approximately 85% of plexiform neurofibromas are considered not amenable to complete resection.7,8,9

About GOMEKLI (mirdametinib)

GOMEKLI is an oral, small molecule MEK inhibitor approved in the United States for the treatment of adult and pediatric patients 2 years of age and older with neurofibromatosis type 1 (NF1) who have symptomatic plexiform neurofibromas (PN) not amenable to complete resection.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Ocular Toxicity: GOMEKLI can cause ocular toxicity including retinal vein occlusion (RVO), retinal pigment epithelium detachment (RPED), and blurred vision. In the adult pooled safety population, ocular toxicity occurred in 28% of patients treated with GOMEKLI: 21% were Grade 1, 5% were Grade 2 and 1.3% were Grade 3. RVO occurred in 2.7%, RPED occurred in 1.3%, and blurred vision occurred in 9% of adult patients. In the pediatric pooled safety population, ocular toxicity occurred in 19% of patients: 17% were Grade 1 and 1.7% were Grade 2. Conduct comprehensive ophthalmic assessments prior to initiating GOMEKLI, at regular intervals during treatment, and to evaluate any new or worsening visual changes such as blurred vision. Continue, withhold, reduce the dose, or permanently discontinue GOMEKLI as clinically indicated.

Left Ventricular Dysfunction: GOMEKLI can cause left ventricular dysfunction. GOMEKLI has not been studied in patients with a history of clinically significant cardiac disease or LVEF <55% prior to initiation of treatment. In the ReNeu study, decreased LVEF of 10 to <20% occurred in 16% of adult patients treated with GOMEKLI. Five patients (9%) required dose interruption, one patient (1.7%) required a dose reduction, and one patient required permanent discontinuation of GOMEKLI. The median time to first onset of decreased LVEF in adult patients was 70 days. Decreased LVEF of 10 to <20% occurred in 25%, and decreased LVEF of ≥20% occurred in 1.8% of pediatric patients treated with GOMEKLI. One patient (1.8%) required dose interruption of GOMEKLI. The median time to first onset of decreased LVEF in pediatric patients was 132 days. All patients with decreased LVEF were identified during routine echocardiography, and decreased LVEF resolved in 75% of patients. Before initiating GOMEKLI, assess ejection fraction (EF) by echocardiogram. Monitor EF every 3 months during the first year and then as clinically indicated. Withhold, reduce the dose, or permanently discontinue GOMEKLI based on severity of adverse reaction.

Dermatologic Adverse Reactions: GOMEKLI can cause dermatologic adverse reactions including rash. The most frequent rashes included dermatitis acneiform, rash, eczema, maculo-papular rash and pustular rash. In the pooled adult safety population, rash occurred in 92% of patients treated with GOMEKLI and required permanent discontinuation in 11% of adult patients. In the pooled pediatric safety population, rash occurred in 72% of patients treated with GOMEKLI and resulted in permanent discontinuation of GOMEKLI in 3.4% of patients. Initiate supportive care at first signs of dermatologic adverse reactions. Withhold, reduce the dose, or permanently discontinue GOMEKLI based on severity of adverse reaction.

Embryo-Fetal Toxicity: GOMEKLI can cause fetal harm when administered to a pregnant woman. Verify the pregnancy status of females of reproductive potential prior to the initiation of GOMEKLI. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Also advise patients to use effective contraception during treatment with GOMEKLI and for 6 weeks after the last dose (females) or 3 months after the last dose (males).

ADVERSE REACTIONS

The most common adverse reactions (>25%) in adult patients were rash (90%), diarrhea (59%), nausea (52%), musculoskeletal pain (41%), vomiting (38%), and fatigue (29%). Serious adverse reactions occurred in 17% of adult patients who received GOMEKLI. The most common Grade 3 or 4 laboratory abnormality (>2%) was increased creatine phosphokinase.

The most common adverse reactions (>25%) in pediatric patients were rash (73%), diarrhea (55%), musculoskeletal pain (41%), abdominal pain (39%), vomiting (39%), headache (34%), paronychia (32%), left ventricular dysfunction (27%), and nausea (27%). Serious adverse reactions occurred in 14% of pediatric patients who received GOMEKLI. The most common Grade 3 or 4 laboratory abnormalities (>2%) were decreased neutrophil count and increased creatine phosphokinase.

USE IN SPECIFIC POPULATIONS

Pregnancy & Lactation. Verify the pregnancy status of patients of reproductive potential prior to initiating GOMEKLI. Due to the potential for adverse reactions in a breastfed child, advise patients not to breastfeed during treatment with GOMEKLI and for 1 week after the last dose.

You are encouraged to report negative side effects of prescription drugs to the FDA. To report suspected adverse reactions, contact SpringWorks Therapeutics at 1-888-400-SWTX (1-888-400-7989) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see accompanying full Prescribing Information for more information.

On February 11, 2025 Vivoryon Therapeutics N.V. (Euronext Amsterdam: VVY; NL00150002Q7) (Vivoryon), a clinical stage company focused on the discovery and development of small molecule medicines to modulate the activity and stability of pathologically altered proteins, reported to host a virtual R&D update with KOL (Key Opinion Leader) speakers on February 18, 2025 (Press release, Vivoryon Therapeutics, FEB 11, 2025, View Source [SID1234650176]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The webcast will include presentations from management and KOLs discussing further analyses and data on varoglutamstat’s observed beneficial effect on kidney function, an update on the Company’s anticipated clinical development plan for varoglutamstat in kidney disease, varoglutamstat’s potential market positioning, and an opportunity for investor and analyst questions.

Featured KOL speakers include:

Tobias B. Huber, MD – Chair of the Center of Internal Medicine and Director of the III. Department of Medicine – University Medical Center Hamburg-Eppendorf (UKE), Germany. Acting as Medical Advisor for clinical study design and certain R&D activities.
Kevin Carroll, PhD – CEO, KJC Statistics. Acting as statistical analysis expert, providing and calculating statistical read-outs and advising on clinical study statistical aspects.
Webcast details

Date: February 18, 2025

Time: 3:00 pm CET / 9:00 am EST

Further details of the event and participation information are available at: View Source

About Varoglutamstat
Varoglutamstat (PQ912) is a proprietary, potent and selective inhibitor of human glutaminyl cyclases QPCT and QPCTL with therapeutic potential in indications including inflammatory and fibrotic diseases, neurodegenerative diseases, cancer and others. Initially advanced development aiming to treat Alzheimer’s disease (AD), varoglutamstat has been investigated in a number of different clinical studies. Based on the known anti-inflammatory and anti-fibrotic activity of varoglutamstat, the protocol for the Phase 2b VIVIAD study in early AD included the investigation of kidney function (measured using eGFR) and measurement of biomarkers of kidney inflammation and fibrosis to explore the role of QPCT/L inhibition on kidney function. eGFR was also analyzed as a prospectively defined safety parameter in the VIVA-MIND Phase 2 study in the U.S.