Survodutide Phase II trial Shows Groundbreaking Results in Liver Disease due to MASH, with Significant Improvements in Fibrosis

Boehringer Ingelheim has reported that in a Phase II trial, a significant proportion of adults treated with survodutide (BI 456906), up to 83.0%, showed a notable enhancement in metabolic dysfunction-associated steatohepatitis (MASH) compared to only 18.2% in the placebo group [difference in response: 64.8% (with a confidence interval of 51.1% – 78.6%), p<0.0001]. The study successfully achieved its main goal, as survodutide demonstrated a biopsy-verified enhancement in MASH over 48 weeks while avoiding the worsening of fibrosis stages F1, F2, and F3 (mild to moderate or advanced scarring). Furthermore, survodutide also met all secondary objectives, including a significant improvement in liver fibrosis. More comprehensive data will be disclosed in the upcoming months.

Survodutide holds promise as a leading treatment for MASH, a liver disorder associated with various cardiovascular, renal, and metabolic issues. It is a unique glucagon/GLP-1 receptor dual agonist with a novel mode of operation, marking the first instance of such significant advantages observed in a Phase II MASH study. The glucagon aspect of survodutide shows the potential to boost energy expenditure and directly influence the liver, which could aid in reducing fibrosis. Meanwhile, the GLP-1 component reduces hunger and enhances feelings of fullness and satisfaction.

Survodutide is currently undergoing assessment in five Phase III trials for individuals who are dealing with overweight and obesity across specific subgroups. The sub-populations under SYNCHRONIZE-1 and SYNCHRONIZE-2 encompass individuals living with comorbidities, those without, and those with type 2 diabetes, respectively. In the SYNCHRONIZE-CVOT trial, the focus is on individuals living with cardiovascular disease, chronic kidney disease, or those with risk factors for cardiovascular disease. Additionally, Boehringer Ingelheim is investigating survodutide in Phase III trials in Japan (SYNCHRONIZE-JP) and China (SYNCHRONIZE-CN) for sub-populations of people facing obesity.

GSK Announces Positive Headline Results from EAGLE-1 Phase III Trial for Gepotidacin in Uncomplicated Urogenital Gonorrhea

GSK plc has reported favorable initial findings from the crucial EAGLE-1 phase III study concerning gepotidacin, a promising potential oral antibiotic that could be a pioneering treatment option for uncomplicated urogenital gonorrhea in both adolescents and adults. This trial successfully achieved its main goal, showing that gepotidacin (administered orally in two 3,000mg doses) was just as effective as the standard treatment of intramuscular (IM) ceftriaxone (500mg) alongside oral azithromycin (1,000mg)—a commonly used combination for treating gonorrhea. The assessment was centered on the primary outcome of microbiological response (either success or failure) during the Test-of-Cure (ToC) visit, which occurs 3-7 days after treatment.

Gonorrhoea, a bacterial infection caused by Neisseria gonorrhoeae, is transmitted through sexual contact. Approximately 82 million new cases occur worldwide annually. In the United States, reported cases of gonorrhea have surged by 118% between 2009 and 2021, with 648,056 instances documented by the US Centers for Disease Control and Prevention (CDC) in 2022. This infection impacts both genders and when untreated or improperly treated, it can result in infertility and various sexual and reproductive health issues. Furthermore, it heightens the likelihood of contracting HIV.

GSK is working on the development of gepotidacin as a possible remedy for uncomplicated urinary tract infections (uUTI). Encouraging results from the EAGLE-2 and EAGLE-3 trials, both in phase III, were unveiled at the European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) in Copenhagen in April 2023. These findings were later published in The Lancet. Should it receive approval, gepotidacin might become the pioneer of a fresh category of oral antibiotics for uUTI, marking the first advancement in over two decades.

Dupixent sBLA Accepted for FDA Priority Review for Treatment of COPD with Type 2 Inflammation

The FDA has agreed to prioritize the review of the additional Biologics License Application (sBLA) for Dupixent (dupilumab) in a potential sixth use, proposing it as a supplementary maintenance therapy for specific adults dealing with uncontrolled chronic obstructive pulmonary disease (COPD). The FDA is expected to decide by June 27, 2024. Similar submissions are currently being assessed in China and the European Union.

The submission for sBLA, alongside similar submissions worldwide, draws upon data from the Phase III COPD clinical investigation of Dupixent’s effectiveness and safety in adults with uncontrolled COPD, either current or former smokers exhibiting evidence of type 2 inflammation (identified through screening blood eosinophils >300 cells/microliter). All participants were receiving maximum standard-of-care inhaled therapy (with nearly all on triple therapy). Both trials (BOREAS, NOTUS) achieved the primary objective, demonstrating that Dupixent notably reduced annualized moderate or severe acute COPD exacerbations by 30% and 34% respectively, when compared to a placebo. Furthermore, Dupixent led to swift and significant enhancements in lung function compared to the placebo in both trials, and these improvements were sustained for up to 52 weeks.

The safety findings in both studies mostly aligned with Dupixent’s established safety record in its authorized uses. More frequent adverse events linked to Dupixent (≥5%) than to placebo in either study included back pain, COVID-19, diarrhea, headache, and nasopharyngitis.

Biogen’s QALSODY® (tofersen) Received a Positive Opinion from CHMP For the Treatment of Amyotrophic Lateral Sclerosis

Biogen disclosed on February 23, 2024, that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has endorsed a positive opinion, recommending marketing authorization for QALSODY® (tofersen). This recommendation is specific to the treatment of adults suffering from Amyotrophic Lateral Sclerosis (ALS) linked to a mutation in the superoxide dismutase 1 (SOD1) gene, and it’s granted under exceptional circumstances. If approved by the European Commission (EC), QALSODY will become the pioneering treatment sanctioned in the European Union to address a genetic cause of Amyotrophic Lateral Sclerosis, also known as motor neuron disease (MND). Biogen acquired the license for QALSODY from Ionis Pharmaceuticals, Inc., through a collaborative development and license agreement. It’s worth noting that Ionis Pharmaceuticals, Inc. is credited with the discovery of QALSODY.

The CHMP’s recommendation for QALSODY stems from a comprehensive assessment of evidence, incorporating various factors such as its targeted mechanism of action, biomarker data, and clinical trial results. Notably, findings from the 28-week Phase 3 VALOR study revealed promising outcomes. Participants administered with QALSODY exhibited a notable 60% decrease in plasma neurofilament light chain (NfL) levels compared to those in the placebo group, indicating a potential reduction in neuronal damage. Moreover, there were observable trends indicating enhanced physical abilities among QALSODY recipients, as evidenced by improvements in scores on the ALS Functional Ratings Scale-Revised (ALSFRS-R) when contrasted with those who received a placebo.

Apart from the continuation of the Phase 3 VALOR study through its open-label extension (OLE), QALSODY is currently under investigation in the Phase 3 ATLAS study, which is randomized and placebo-controlled. This study aims to assess whether QALSODY has the potential to postpone the clinical onset of symptoms when administered to presymptomatic individuals carrying a SOD1 genetic mutation, along with biomarker indications of disease activity such as elevated plasma neurofilament light chain (NfL) levels.

The CHMP’s recommendation for QALSODY will undergo review by the European Commission (EC) to determine marketing authorization within the European Union. A decision regarding this authorization is anticipated to be reached in the second quarter of 2024.

“The CHMP’s positive opinion reinforces the impact QALSODY can have in SOD1-ALS and further demonstrates Biogen’s commitment to address the unmet needs of people living with ALS and neuromuscular diseases. We are proud to help pioneer the role of neurofilament in SOD1-ALS clinical trials and are deeply grateful to the people living with SOD1-ALS, their loved ones, and study care teams for their dedication to furthering research for the ALS community.”

Priya Singhal, M.D., M.P.H., Head of Development at Biogen

“The CHMP’s recommendation in support of QALSODY approval provides new hope for the ALS community in Europe. This is a significant milestone for the entire ALS community – for the first time we have a treatment that led to sustained reductions in neurofilament, a marker of axonal injury and neurodegeneration. The QALSODY development program has provided critical learnings on clinical trial design and the use of biomarkers that is advancing the entire field.”

Philip Van Damme, M.D., Ph.D., professor of neurology and director of the Neuromuscular Reference Center at the University Hospital Leuven in Belgium

Amyotrophic Lateral Sclerosis (ALS) stands as a rare, progressively debilitating neurological disorder leading to the deterioration of motor neurons within the brain and spinal cord, impairing voluntary muscle movement. Identified mutations within the SOD1 gene contribute to roughly 2 percent of Amyotrophic Lateral Sclerosis cases worldwide, denoted as SOD1-ALS. While over 15 percent of Amyotrophic Lateral Sclerosis cases are believed to have a genetic component, individuals may not necessarily possess a documented family history of the ailment.

According to DelveInsight, the diagnosed prevalent cases of Amyotrophic Lateral Sclerosis in the 7MM (Seven Major Markets) and China exceeded 59,100 and 29,000 respectively in 2021, with projections indicating a rise in cases in the forthcoming years. Epidemiological evaluations have highlighted the United States alone accounting for approximately 25,800 diagnosed prevalent cases of Amyotrophic Lateral Sclerosis in 2021.

Various prominent pharmaceutical and biotechnology enterprises, including Biogen and others, are actively engaged in research and development efforts within the Amyotrophic Lateral Sclerosis market, striving to address the prevailing unmet medical needs. Consequently, the therapeutic landscape and treatment prospects for Amyotrophic Lateral Sclerosis are poised to witness significant advancements in the near future with the introduction of novel therapies.

Immune-Onc Therapeutics Announces Orphan Drug Designation Granted by US FDA for IO-202 For the Treatment of Chronic Myelomonocytic Leukemia (CMML)

Immune-Onc Therapeutics made a significant announcement on February 21, 2024, revealing that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation to their groundbreaking compound, IO-202, aimed at tackling Chronic Myelomonocytic Leukemia (CMML). This designation underscores the potential of IO-202 as a vital therapeutic option for patients grappling with CMML, a challenging hematologic malignancy.

IO-202’s journey to FDA recognition has been marked by notable milestones. Notably, in 2023, it was granted with Fast Track Designation for its efficacy in addressing relapsed or refractory Chronic Myelomonocytic Leukemia, further highlighting the urgency and significance of its development. Moreover, the FDA had previously granted both Fast Track and Orphan Drug Designations to IO-202 for its potential in combating acute myeloid leukemia (AML) in 2022 and 2020, respectively.

This string of designations underscores the growing recognition of IO-202’s promise in the realm of hematologic cancers. With each designation, IO-202’s status as a potential game-changer in leukemia treatment is further solidified, offering hope to patients and clinicians alike in the ongoing battle against these complex diseases.

IO-202 represents a pioneering antagonist antibody with a distinct mechanism of action, demonstrating a high degree of specificity and affinity for the Leukocyte Immunoglobulin-Like Receptor subfamily B4 (LILRB4). This targeted therapeutic approach holds immense promise across a spectrum of conditions, including blood cancers, autoimmune disorders, and inflammatory diseases.

Currently, IO-202 is undergoing evaluation in a Phase 1 dose expansion clinical trial (NCT04372433), where it is being assessed in conjunction with azacitidine (AZA) for newly diagnosed patients with Chronic Myelomonocytic Leukemia (CMML) who have not been treated with hypomethylating agents (HMA). Notably, a dose escalation study of IO-202 has already been completed, demonstrating its clinical efficacy both as a standalone treatment and in combination with AZA for patients with relapsed or refractory Acute Myeloid Leukemia (AML) and Chronic Myelomonocytic Leukemia (CMML).

Encouragingly, IO-202 has exhibited favorable tolerability profiles in all patients enrolled in trials conducted thus far, indicating its potential as a well-tolerated therapeutic option across diverse patient populations.

“Although current therapeutic options for CMML can improve a patient’s quality of life, there is a high unmet need for effective disease-modifying approaches that are potentially curative. We are very proud that the FDA has granted IO-202 Orphan Drug Designation for the treatment of CMML. We look forward to continued collaborations with our investigators and the FDA as we work to bring this potentially important therapy to patients with hard-to-treat blood cancers.”

Charlene Liao Ph.D., chief executive officer and board chair of Immune-Onc

Chronic Myelomonocytic Leukemia represents a rare hematologic malignancy, with an incidence rate of approximately 4 cases per 1,000,000 individuals annually in the United States, translating to roughly 1,100 new cases each year. Currently, the FDA-approved armamentarium for CMML primarily consists of hypomethylating agents, such as azacitidine, which aim to manage the disease without significantly impacting overall survival rates.

However, there exists a pressing need for novel therapeutic approaches that can potentially offer substantial improvements in Chronic Myelomonocytic Leukemia management and patient outcomes. Both pharmaceutical and biotechnology companies are actively engaged in the exploration of innovative treatments tailored specifically for CMML.

Promising candidates on the horizon such as IO-202, alongside other emerging therapies, are poised to revolutionize the landscape of Chronic Myelomonocytic Leukemia treatment. The anticipated introduction of these novel treatments holds the potential to significantly alter the outlook for Chronic Myelomonocytic Leukemia patients, offering renewed hope and improved prospects for managing this challenging disease.

Artiva Biotherapeutics Receives FDA Fast Track Designation for AlloNK® in Lupus Nephritis

Artiva Biotherapeutics made a significant stride in the realm of medical advancements on February 21, 2024. The company announced that the U.S. Food and Drug Administration (FDA) had granted Fast Track designation upon its groundbreaking lead program, AlloNK® (also identified as AB-101). This designation is specifically for the treatment of Lupus Nephritis (LN), a severe manifestation of systemic lupus erythematosus, when used in conjunction with rituximab or obinutuzumab.

This announcement comes on the heels of Artiva’s previous milestone: the FDA’s clearance of an Investigational New Drug (IND) application for AlloNK in combination with rituximab for the treatment of LN. This clearance was a historic moment as it marked the first instance of FDA clearance for an allogeneic, off-the-shelf NK (natural killer) cell therapy in the context of autoimmune disease.

The Fast Track designation by the FDA represents a recognition of the urgent need for effective treatments for Lupus Nephritis, a condition that significantly impacts patients’ quality of life and has been historically challenging to treat. This designation expedites the review process of AlloNK®, potentially accelerating its availability to patients in need. With this significant regulatory milestone achieved, Artiva Biotherapeutics is poised to embark on the next phase of clinical development, bringing hope to countless individuals grappling with the burdensome effects of LN.

AlloNK® (also referred to as AB-101) represents an allogeneic NK cell therapy candidate meticulously engineered to augment the antibody-dependent cellular cytotoxicity (ADCC) mechanism of monoclonal antibodies or NK cell engagers. Characterized as a cryopreserved, readily available therapy, AlloNK holds the potential for administration in community healthcare settings. Notably, AlloNK is developed without genetic modification and is manufactured devoid of integrating vectors, thereby bypassing the need for extensive patient monitoring and mitigating concerns regarding secondary malignancy, a common issue associated with approved autologous CAR-T therapies.

Utilizing Artiva’s cell therapy manufacturing platform, the company can produce numerous doses of cryopreserved, infusion-ready AlloNK cells from a single umbilical cord blood unit. This process ensures the retention of consistently high expression levels of CD16 and activating NK receptors, thus maintaining the therapy’s efficacy and potency across batches.

“The FDA Fast Track designation gives us an opportunity to accelerate our efforts to bring our AlloNK cell therapy to autoimmunity patients. We are encouraged by clinical data from our Phase 1/2 multicenter clinical trial in non-Hodgkin lymphoma, where we observed that AlloNK in combination with rituximab can drive deep B-cell depletion in patients with late-line B-cell cancers. Our therapy has a mechanism very similar to the B-cell targeted autologous CAR-T therapies, but with the benefits of being an off-the-shelf therapy with a better safety profile, and that we believe will not be subject to the secondary malignancy risk associated with genetically engineered cell therapies.” 

Fred Aslan, M.D., Chief Executive Officer of Artiva

AlloNK is currently under investigation in a multi-center, open-label clinical trial aimed at evaluating its safety and clinical efficacy when combined with anti-CD20 antibodies in patients diagnosed with Lupus Nephritis (LN) who have either relapsed or shown inadequate response to previous standard treatment approaches. Furthermore, the safety and efficacy of AlloNK in combination with rituximab have been demonstrated in a Phase 1/2 multicenter clinical trial involving patients with relapsed or refractory B-cell-non-Hodgkin lymphoma (B-NHL). 

According to DelveInsight, the total number of diagnosed prevalent cases of Systemic lupus erythematosus (SLE) across the 7 Major Markets (7MM) was estimated to be around 657,000 cases in the year 2022. It is projected that this number will continue to rise over the forecast period. Notably, the United States constituted the largest portion of prevalent cases of Lupus Nephritis, making up approximately 50% of the total cases in the 7MM in 2022. In contrast, the EU4 countries, the UK, and Japan together accounted for approximately 36% and 14% of the total population share, respectively, in the same year.

The introduction of upcoming therapies such as AlloNK® holds significant promise in revolutionizing the Lupus Nephritis therapeutics market. As these innovative therapies enter the market, they are expected to bring about transformative changes in how the condition is managed, offering new hope and improved outcomes for patients worldwide.