EBGLYSS Receives Positive CHMP Opinion for Moderate-to-Severe Atopic Dermatitis

Almirall S.A. announced that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) issued a positive opinion recommending the marketing authorization of EBGLYSS (lebrikizumab) for the treatment of moderate-to-severe atopic dermatitis in adults and adolescents (12 years and older with a body weight of at least 40 kg) who are candidates for systemic therapy.

The European Commission (EC) is now reviewing the positive CHMP opinion. This biologic is expected to be approved in the European Union within two months, and it might be launched in the first European country soon after. According to the results of the Phase III clinical development program, the majority of patients (80%) who responded to therapy with lebrikizumab at Week 16 weeks maintained skin clearing and itch relief for one year with monthly maintenance dose.

The positive CHMP recommendation for EBGLYSS in moderate to severe Alzheimer’s disease represents an important milestone in bringing a next-generation biologic therapy to people living with atopic dermatitis, providing a much-needed additional treatment option.” We are optimistic that EBGLYSS has the potential to become a first-line treatment for moderate-to-severe atopic dermatitis due to its selective mechanism of action, demonstrated long-term efficacy, and patient-friendly monthly maintenance dose.

Karl Ziegelbauer, Almirall’s Chief Scientific Officer

Almirall has licensed the rights to develop and market lebrikizumab in Europe for dermatological indications such as atopic dermatitis. Eli Lilly and Company has sole rights to the product’s development and commercialization in the United States and the rest of the globe, excluding Europe. Almirall anticipates regulatory decisions in additional European markets, including the United Kingdom and Switzerland, for lebrikizumab in moderate-to-severe atopic dermatitis in 2024.

FDA Approves Ojjaara as the First and Only Treatment Indicated for Myelofibrosis Patients with Anemia

GSK plc announced that the US Food and Drug Administration (FDA) has approved Ojjaara (momelotinib) for the treatment of intermediate or high-risk myelofibrosis in adults with anemia, including primary myelofibrosis or secondary myelofibrosis (post-polycythemia vera and post-essential thrombocythaemia). Ojjaara is an oral JAK1/JAK2 and activin A receptor type 1 (ACVR1) inhibitor that is taken once a day. It is now the only licensed drug for both newly diagnosed and previously treated myelofibrosis patients with anemia that tackles the disease’s major signs, namely anemia, constitutional symptoms, and splenomegaly (enlarged spleen).

The vast majority of myelofibrosis patients eventually develop anemia, causing them to discontinue treatments and require transfusions,” said Nina Mojas, Senior Vice President, Oncology Global Product Strategy, GSK. We are excited to add Ojjaara to our cancer portfolio and address a substantial medical need in the community, given the high unmet need. We are excited to contribute to better results in this difficult-to-treat blood malignancy.

Momelotinib was approved by the FDA based on findings from the key MOMENTUM study and a subset of adult patients with anemia from the SIMPLIFY-1 phase III trial. MOMENTUM was meant to compare the safety and efficacy of momelotinib versus danazol in treating and reducing major symptoms of myelofibrosis in an anemic, symptomatic, JAK inhibitor-experienced population. The MOMENTUM trial accomplished all of its primary and major secondary objectives, revealing a statistically significant response in individuals treated with momelotinib versus danazol in terms of constitutional symptoms, splenic response, and transfusion independence. SIMPLIFY-1 was aimed to compare the efficacy and safety of momelotinib versus ruxolitinib in individuals with myelofibrosis who had not previously received JAK-inhibitor therapy. SIMPLIFY-1 safety and efficacy data were based on a subset of anemia patients. Momelotinib is not presently available in any other market.

EMA Grants PRIME Designation to Iopofosine I-131 for Waldenström Macroglobulinemia

The European Medicines Agency (EMA) has granted Priority Medicines (PRIME) status to iopofosine I-131, formerly known as CLR 131, for use in patients with Waldenström macroglobulinemia who have received at least two prior treatment regimens.

Phospholipids make up the structural basis of cell membranes and their levels increase during the development of cancer and tumor progression. Iopofosine I-131 is taken up by specific lipid-rich areas (raft microdomains) on tumor cells, accumulating in the cytoplasm. This unique mechanism enables the drug to spare normal tissues while delivering iodine-131 directly into cancer cells, inducing apoptosis.

Currently, the safety and effectiveness of this phospholipid drug conjugate are being investigated in patients with certain B-cell malignancies as part of the phase 2 CLOVER-1 trial (NCT02952508). There is a specific focus on Waldenström macroglobulinemia (CLOVER-WaM) within this trial. Anticipated to conclude in the latter half of 2023, the trial has two parts: Part A, an open-label study involving various B-cell malignancies, and Part B, focusing on Waldenström macroglobulinemia patients who have undergone at least two prior lines of therapy.

Eligible participants must be at least 18 years old, possess an ECOG performance status of 0 to 2, have a life expectancy of at least 6 months, and meet specific blood count and organ function criteria.

In Part A of the trial, the primary goal was to assess clinical benefit rate (CBR), with secondary objectives including overall response rate (ORR), progression-free survival, time to next treatment, overall survival, and duration of response (DOR). For Part B, the main endpoint was the major response rate, with additional secondary endpoints such as ORR, treatment-free survival, DOR, and CBR.

FDA Accepts Resmetirom NDA, Grants Priority Review, and Sets PDUFA Date

The FDA has agreed to review the new drug application (NDA) for resmetirom, a product by Madrigal Pharmaceuticals, intended for treating adults suffering from nonalcoholic steatohepatitis (NASH) with liver fibrosis. This investigational drug has been given priority status by the agency and a Prescription Drug User Fee Act target date has been set for March 14, 2024, as announced in a company press release.

NASH, a primary contributor to liver-related fatalities, represents an advanced stage of nonalcoholic fatty liver disease (NAFLD), a condition estimated to impact around 30% of adults in the United States. Among individuals with NAFLD, approximately 20% may progress to NASH. Adults with NASH, particularly those dealing with concurrent metabolic risk factors like hypertension and type 2 diabetes, face a significantly heightened risk of adverse cardiovascular events.

Resmetirom is an oral medication taken once daily, functioning as a selective agonist for thyroid hormone receptor (THR)-β. It addresses a key underlying cause of NASH in the liver, which is impaired THR activity. The compromised THR action leads to reduced mitochondrial function and a decrease in beta-oxidation of fatty acids. The latter exacerbates inflammation and fibrotic changes within the liver, as outlined in the company’s release.

The progression of NASH to substantial liver fibrosis (stages F2 and F3) substantially amplifies the risk of adverse hepatic outcomes, making it a primary cause of liver transplantation in the US. Despite numerous agents progressing to phases 2 and 3 clinical trials, there are currently no FDA-approved treatments available for NASH, according to Madrigal.

The NDA by Madrigal is grounded in the pivotal phase 3 MAESTRO-NASH clinical trial, where resmetirom successfully achieved both primary endpoints pertaining to histologic improvement: resolution of NASH and reduction of liver fibrosis. These endpoints had been suggested by the FDA to support accelerated approval for treating NASH with liver fibrosis. In both the MAESTRO-NASH trial and the phase 3 safety study MAESTRO-NAFLD-1, resmetirom demonstrated reduced levels of LDL cholesterol and triglycerides, along with potentially significant enhancements in noninvasive indicators of liver health, as highlighted by the company.

The MAESTRO-NASH study involved approximately 1750 patients and is ongoing, evaluating patients beyond the initial 52-week treatment phase for up to 54 months. This extended phase of the study is designed to collect validating data and assess hepatic clinical outcomes, including progression to biopsy-confirmed cirrhosis, hepatic decompensation events, and all-cause mortality. Additionally, a separate 52-week phase 3 clinical trial, an open-label active treatment extension study of MAESTRO-NAFLD-1 (MAESTRO-NAFLD-OLE), involving 700 patients, is also in progress.

Kymera Receives UA FDA Fast Track Designation for KT-333 for the Treatment of R/R CTCL & PTCL

Kymera Therapeutics, Inc. (NASDAQ: KYMR) announced disclosed on September 18, 2023, that the U.S. Food and Drug Administration (FDA) has granted Fast Track status to KT-333 for the treatment of R/R Peripheral T-cell Lymphoma (PTCL) and R/R Cutaneous T-cell Lymphoma (CTCL).

KT-333, currently in development, is a profoundly selective protein degrader designed to target STAT3. Its purpose is to address various conditions driven by STAT3, encompassing hematological malignancies and solid tumors. STAT3 serves as a transcriptional regulator implicated in a wide range of cancers, as well as inflammatory and autoimmune disorders. In the year 2022, KT-333 secured FDA orphan drug designation for the management of both CTCL and PTCL.

The KT-333 Fast Track designation highlights the promise of degrading STAT3, a protein that has historically been undruggable, for the treatment of patients with CTCL and PTCL. We look forward to providing an update on the KT-333 Phase 1 clinical trial later this year, including initial evaluation of its antitumor activity in the target patient populations, and to working with the lymphoma community to rapidly advance this first-in-class heterobifunctional degrader in CTCL and PTCL in addition to exploring its potential in other cancers.

Jared Gollob, MD, Chief Medical Officer, Kymera Therapeutics.

The Phase 1 clinical trial for KT-333 has been structured to assess the safety, tolerance, pharmacokinetics/pharmacodynamics (PK/PD), and clinical effectiveness of weekly doses of KT-333 in adult patients dealing with recurrent and/or resistant forms of lymphomas, leukemias, and solid tumors. In June, during the International Conference on Malignant Lymphoma (ICML), Kymera presented findings based on data from thirteen patients who had received an average of five doses spanning the initial four dose levels (DL1-4) in the trial. This group of patients encompassed individuals with solid tumors, CTCL, and PTCL. As of the presentation, DL4 was still open for patient recruitment.

PTCL, classified as a subtype of non-Hodgkin’s lymphoma, comprises a diverse range of tumors originating from mature T-cells within lymphoid tissues located in various parts of the body, including lymph nodes, lungs, the gastrointestinal tract, and the skin. As per DelveInsight, the total incident population of PTCL in the 7MM was found to be 18,000+ in 2021. In the United States, approximately 4,000 to 8,000 individuals receive a PTCL diagnosis annually, and PTCL constitutes 15% to 20% of the cases categorized as aggressive lymphomas in the U.S. The total incident population of PTCL in the United States was 6,300+ in 2021 and the cases are projected to increase during the forecast period. To provide an effective therapeutic option, companies like Kymera, among several others, are actively working in the PTCL therapeutics market

RedHill Announces FDA sNDA Approval for Talicia®

On September 18, 2023, RedHill Biopharma Ltd. (Nasdaq: RDHL) (“RedHill” or the “Company”) made an announcement regarding the approval of its supplemental new drug application (sNDA) for Talicia by the US FDA. This approval allows for a shift to a more flexible dosing regimen for H. pylori eradication, with the medication now to be taken three times daily (TID), with at least 4 hours between doses and with food. This differs from the previously approved regimen (Q8H), which required dosing every eight hours with food. The new regimen permits patients to adhere to a more convenient schedule, aligning with their breakfast, lunch, and dinner, which may enhance patient compliance and increase the chances of successfully eliminating H. pylori.

H. pylori treatment can be challenging for patients, as most regimens require different pills to be taken multiple times per day. However, it is clear that simplified regimens promote improved patient adherence and should be a key factor when considering the choice of H. pylori eradication therapy. This new dosing regimen further supports the value of Talicia as an empirically prescribed first-line therapy for H. pylori eradication. Talicia’s favorable efficacy, tolerability, and resistance profile, as well as being the only all-in-one formulation available, provides potential advantages over clarithromycin-based regimens for most patients.

Colin W. Howden, MD, Professor Emeritus, University of Tennessee College of Medicine

Talicia is unique in that it is the only FDA-approved rifabutin-based therapy for the eradication of H. pylori. Both its components and formulation are optimized to provide patients with the necessary medications for successful H. pylori eradication. RedHill is committed to advancing GI and infectious disease management through patient-focused innovation. Through our successful collaboration with Certara, utilizing their Simcyp™ Simulator for physiologically based pharmacokinetic (PBPK) modeling, we have demonstrated therapeutic equivalence between TID and Q8H dosing, enabling us to provide what we believe is a more flexible Talicia regimen that we believe will be beneficial for the patient experience.

Dr. June Almenoff, MD, Ph.D., RedHill’s Chief Medical Officer

Talicia represents an innovative oral capsule formulation that combines two antibiotics (amoxicillin and rifabutin) with a proton pump inhibitor (PPI) called omeprazole. In a significant Phase 3 clinical trial, Talicia exhibited an impressive 84% rate of eradicating H. pylori infection in the intent-to-treat (ITT) group, as opposed to 58% in the comparison group receiving an alternative treatment (p<0.0001). It’s worth noting that the pivotal Phase 3 study conducted by RedHill showed minimal to no evidence of resistance to rifabutin, which is a critical component of Talicia.

Talicia has been granted a Qualified Infectious Disease Product (QIDP) designation, providing it with a comprehensive eight-year period of exclusive marketing rights in the United States. Additionally, it benefits from U.S. patents that extend its patent protection until 2034, and there are ongoing patent applications and granted patents in multiple regions around the world, further bolstering its global protection.

Globally, over 50% of the world’s population is affected by H. pylori. In the US, around 35% of the population is impacted by H. pylori. Roughly two million patients receive treatment for it each year. The eradication of H. pylori is becoming increasingly challenging, as current therapies fail in approximately 25-40% of patients, resulting in persistent H. pylori infection. This persistence is primarily due to the elevated resistance of H. pylori to antibiotics, especially clarithromycin, which remains a common component of standard combination treatments. To overcome the existing unmet need and the therapeutics challenges, companies such as RedHill Biopharma and others are actively working in the H. pylori therapeutic segment.