According to the findings of this phase IIIb, open-label single-arm study, 56.3% of patients who received risankizumab without a washout period after suboptimal response to secukinumab or ixekizumab achieved the primary endpoint of reduced signs and symptoms of psoriasis (sPGA 0/1). After at least six months of treatment with secukinumab or ixekizumab, a suboptimal response was defined as a static Physician’s Global Assessment (sPGA) score of 2 or 3 and a decrease in body surface area of 3% to 10%. The average length of treatment for patients receiving secukinumab was 2.6 years, and 2.1 years for patients receiving ixekizumab.
Among the highlights of this new aIMM 52-week analysis are:
- At the week 52 primary endpoint, most patients (63.0%) had clear or nearly clear skin (sPGA 0/1).
- A secondary endpoint was achieved by patients who had completely clear skin (sPGA score of 0) at weeks 16 (19.8%) and 52 (26.2%).
- A Psoriasis Symptom Scale (PSS) score of 0 at week 16 (20.2%) and week 52 (27.4%) indicated that patients had no symptoms such as pain, itching, redness, or burning.
Arrowhead Receives FDA Fast Track Designation for ARO-APOC3
Arrowhead Pharmaceuticals Inc. announced that the FDA had granted ARO-APOC3 Fast Track designation for lowering triglycerides in adult patients with familial chylomicronemia syndrome (FCS). The FDA and the European Union previously designated ARO-APOC3 as an orphan drug.
Arrowhead’s investigational RNAi therapeutic ARO-APOC3 is being developed as a treatment for patients with severe hypertriglyceridemia (SHTG), mixed dyslipidemia (MD), and FCS. FCS is a rare genetic disorder characterized by severely elevated triglyceride levels that can lead to acute and potentially fatal pancreatitis. There are currently no FDA-approved treatments for FCS.
The prevalence of severe hypertriglyceridemia (SHTG) has increased manifolds in recent years. As per DelveInsight’s latest “Severe Hypertriglyceridemia Epidemiology Forecast” report, there were nearly 3.4 million diagnosed prevalent cases of SHTG in the 7MM in 2022. Severe hypertriglyceridemia can be caused due to secondary factors, but nearly 45% of cases are due to genetic predisposition, where familial chylomicronemia syndrome is a significant condition. Due to overlapping blood triglyceride levels and comparable symptoms, it is challenging to identify familial chylomicronemia syndrome distinctly. As per DelveInsight’s latest “Familial Chylomicronemia Syndrome Epidemiology Forecast” report, familial chylomicronemia syndrome prevalence ranges from 1–4 per million, with around 2,082 cases diagnosed prevalent cases in the 7MM in 2022.
ARO-APOC3 is being studied in the Phase III PALISADE clinical study (NCT05089084) in patients with FCS, the Phase II SHASTA-2 clinical study (NCT04720534) in patients with SHTG, and the Phase II MUIR clinical study (NCT04998201) in patients with MD.
FDA Approves Dabrafenib Plus Trametinib for Pediatric Patients With BRAF V600E–Mutated Low-Grade Glioma
Novartis announced that the FDA had approved Tafinlar® (dabrafenib) + Mekinist® (trametinib) for the low-grade glioma (LGG) treatment of pediatric patients 1 year of age and older with a BRAF V600E mutation who require systemic therapy. Tafinlar and Mekinist liquid formulations were also approved by the FDA, marking the first time a BRAF/MEK inhibitor has been developed in a formulation suitable for patients as young as one year old. Tafinlar + Mekinist is now the first and only approved combination targeted therapy for pediatric patients with BRAF V600E LGG.
“Pediatric cancer research is critical to uncovering new treatment methods for a population” (SickKids). “Developing targeted therapies based on a patient’s tumor’s unique genetic features is the future of pediatric cancer care.”
Dr. Eric Bouffet, MD, FRCPC, Principal Investigator of the TADPOLE clinical trial and Associate Scientist Emeritus at The Hospital for Sick Children
The FDA approved Tafinlar + Mekinist based on findings from the Phase II/III TADPOLE trial (NCT02684058), which found that patients randomized to Tafinlar + Mekinist experienced a statistically significant improvement in overall response rate (ORR) of 47% (CI: 35-59%) compared to 11% (CI: 3-25%) for those randomized to chemotherapy. The median progression-free survival (PFS) with Tafinlar + Mekinist was 20.1 months (CI: 12.8 months-not estimable) compared to 7.4 months with chemotherapy (CI: 3.6-11.8 months, hazard ratio=0.31 [CI: 0.17-0.55] [p0.001]).
“It is more important than ever to screen patients with low-grade glioma for genetic mutations. “This FDA approval may provide new hope to pediatric patients suffering from BRAF V600E low-grade glioma,” said Dr. Roger Packer, senior vice president of Children’s National Hospital’s Center for Neurosciences and Behavioral Medicine. “This has the potential to change how healthcare providers treat these pediatric patients, significantly improving chemotherapy.”
FDA Grants ODD to Novel BRAF Inhibitor for Brain/CNS Malignancies
FORE Biotherapeutics (FORE Bio) has announced that the US FDA has granted Orphan Drug Designation (ODD) to its lead program, FORE8394, for the treatment of primary brain and central nervous system (CNS) malignancies. With this approval from the FDA, FORE8394 became the first drug for FORE Bio to receive the orphan drug designation and the FORE8394 program. FORE Biotherapeutics is a precision-stage oncology company dedicated to developing innovative treatments that provide better outcomes for cancer patients.
FORE8394 is an investigational, novel, small-molecule, next-generation, orally available selective inhibitor of mutated BRAF. It was designed to target a wide range of BRAF mutations while sparing wild-type forms of RAF. Preclinical studies and clinical trials have shown that its unique mechanism of action effectively inhibits not only the constitutively active BRAFV600 monomers targeted by first-generation RAF inhibitors but also disrupts constitutively active dimeric BRAF class 2 mutants, fusions, splice variants, and others.
“The receipt of Orphan Drug Designation is another important regulatory achievement that reinforces the FDA’s recognition of the potential of FORE8394 to improve clinical outcomes in patients with BRAF-altered brain tumors. This designation will help us continue to expedite the development of our novel BRAF inhibitor, and we look forward to working closely with the global investigator community supporting FORTE and to advancing the development of FORE8394 for patients in need.”
Stacie Shepherd, M.D., Ph.D., Chief Medical Officer of Fore Biotherapeutics
Unlike first-generation RAF inhibitors, FORE8394 does not induce paradoxical activation of the RAF/MEK/ERK pathway. As a “paradox breaker,” FORE8394 could therefore treat acquired resistance to current RAF inhibitors and, more generally, yield improved safety and more durable efficacy than first-generation RAF inhibitors. The company previously announced interim data from the ongoing Phase 1/2a clinical trial evaluating FORE8394 in advanced solid and CNS tumors with activating BRAF alterations, providing evidence of durable antitumor activity in patients with BRAF-mutated (V600+) cancers.
Earlier, FORE Biotherapeutics presented the data at the European Society of Medical Oncology Congress (ESMO) in September 2022. Mature data from the Phase 1/2a clinical trial is expected in mid-2023. Similarly, in September 2022, FORE8394 was granted Fast Track Designation by the US FDA for the treatment of patients with cancers harboring BRAF Class 1 (V600) and Class 2 (including fusions) alterations who have exhausted prior therapies. The approval and launch of FORE8394 hold immense potential to improve the Brain/CNS Malignancies treatment scenario in the coming years.
EP0042 Wins FDA Orphan Drug Status for Acute Myeloid Leukemia
Ellipses Pharma announces that the US FDA has granted Orphan Drug Designation (ODD) to its drugs, EP0042 for the treatment of acute myeloid leukemia (AML). EP0042 is a dual FLT3 and Aurora kinase inhibitor under development as a new treatment for Acute Myeloid Leukemia patients who have developed FLT3 inhibitor resistance. Dual inhibition of FLT3 and Aurora kinase has overcome acquired resistance to selective FLT3 inhibition in vitro and in vivo. Around one-third of patients with Acute Myeloid Leukemia are diagnosed with FLT3-mutations, which are associated with a higher risk of relapse and poor clinical outcomes. EP0042 is currently being investigated in an adaptive phase 1/2 dose-ranging and optimization study in patients with relapsed / refractory acute myeloid leukemia, and Ellipses plans to further evaluate it as both a potential monotherapy and in combination with standard treatments once a phase 2 dose is confirmed.
“Receiving an FDA Orphan Drug Designation for EP0042 validates this compound’s potential in a currently underserved area of medicine. The designation is an important milestone in the development of EP0042, and underscores the work we are already undertaking towards accelerating its potential access to patients. We believe its early clinical data merits its continued study, and this FDA decision further focuses our vision as we continue our drive towards bringing EP0042 to more patients.”
Dr. Rajan Jethwa, Chief Executive Officer & Co-Founder of Ellipses
Preliminary data from this study were presented at the 64th American Society of Hematology (ASH) Annual Meeting in December 2022, which demonstrated acceptable safety and tolerability for EP0042, and evidence of prolonged disease control in a number of heavily pre-treated Acute Myeloid Leukemia patients. Earlier, in February 2023, the FDA approved EP0042’s Investigational New Drug Application, which allowed for the opening of additional trial sites in the US for this compound.
Acute Myeloid Leukemia is one of the most common types of leukaemia in adults and approximately 20,000 patients are diagnosed with Acute Myeloid Leukemia in the US each year and 18,000 patients in Europe, with around 40% of cases being diagnosed in people over the age of 75. Moreover, as per the estimate, in 2017, among the EU5 countries, the UK has the highest prevalence of Acute Myeloid Leukemia, at more than 5,000 cases, while Spain has the lowest at under 2,300 cases. Several companies are actively working in the Acute Myeloid Leukemia market to improve the treatment scenario. Among various pipeline therapies, emerging therapies such as EP0042 and others hold immense potential to improve the Acute Myeloid Leukemia therapeutics scenario.
Karuna Therapeutics Announces Positive Results from Phase 3 EMERGENT-3 Trial of KarXT in Schizophrenia
On March 20, 2023, Karuna Therapeutics, Inc. (NASDAQ: KRTX) announced positive topline results from its Phase 3 EMERGENT-3 trial evaluating the efficacy, safety, and tolerability of its lead investigational therapy, KarXT (xanomeline-trospium) for the treatment of schizophrenia.
The Phase 3 EMERGENT-3 trial is a double-blind, placebo-controlled, five-week, inpatient trial evaluating the efficacy, safety, and tolerability of KarXT, compared to a placebo in adults with schizophrenia in the United States and Ukraine. The primary endpoint was a change from baseline in the Positive and Negative Syndrome Scale (PANSS) total score, a scale measuring schizophrenia symptom severity, of KarXT compared to placebo at Week 5. Prespecified secondary endpoints included change from baseline in PANSS positive, PANSS negative and PANSS negative Marder factor subscale of KarXT compared to placebo at Week 5. A total of 256 adults (between the ages of 18–65 years) with schizophrenia enrolled in the trial. Enrolled patients had a confirmed diagnosis of schizophrenia and were experiencing symptoms of psychosis at the time of enrollment.
“KarXT has now demonstrated a robust and consistent reduction of symptoms across all three registrational trials, providing a compelling picture of the potential of KarXT in schizophrenia. With these data, we are one step closer to a potential treatment option that could provide the first new mechanism of action to treat schizophrenia in several decades
Bill Meury, president and chief executive officer (Karuna Therapeutics)
The NDA submission for KarXT in schizophrenia will incorporate the efficacy and safety data from the three placebo-controlled registrational trials, EMERGENT-1, EMERGENT-2, and EMERGENT-3, in addition to long-term safety data from the ongoing EMERGENT-4 and EMERGENT-5 trials.
As per DelveInsight, in the year 2021, the total prevalent cases of Schizophrenia were 6.27 million in the 7MM which are expected to grow in the coming years. Globally, several major pharma and biotech companies are actively working in the Schizophrenia therapeutics market. Several of the emerging therapies are in the advance stage of clinical development, expected to hit the market in the near future. As per the update from Karuna Therapeutics, the company is on track to submit an NDA to the FDA for its drugs, KarXT in mid-2023, with a potential launch in the second half of 2024, if approved.
