Significant improvements, both statistically (p<0.0001) and clinically meaningful, were observed in all 10 predetermined secondary endpoints. These included enhancements in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) at weeks 12 and 24, an increase in the proportion of patients with a class improvement of ≥1 in New York Heart Association (NYHA) functional class at weeks 12 and 24, alterations in provoked left ventricular outflow tract gradient (LVOT-G) and the proportion below 30 mmHg at weeks 12 and 24, as well as improvements in exercise workload and eligibility for septal reduction therapy based on guidelines.
“The outcomes of the SEQUOIA-HCM study have exceeded our expectations in terms of both effectiveness and safety. Aficamten, when added to standard care therapy, demonstrated a favorable impact on exercise capacity and exhibited prompt and sustained effects on symptoms and functional class in patients with obstructive HCM. These positive effects were achieved while maintaining the safety and tolerability observed in previous assessments. Dr. Fady I. Malik, Cytokinetics’ Executive Vice President of Research & Development, expressed confidence in the results, stating that they align with findings from the Phase 2 trial (REDWOOD-HCM) and the ongoing open-label extension trial (FOREST-HCM). He believes that these results may establish aficamten as the preferred cardiac myosin inhibitor among both physicians and patients. Dr. Malik expressed gratitude to the patients, investigators, and site personnel involved in SEQUOIA-HCM, emphasizing ongoing support for clinical research. The complete findings from this trial are anticipated to be shared at a medical meeting in 2024.”
Chiesi Global Rare Diseases Receives FDA Approval for FILSUVEZ Topical Gel for the Treatment of Epidermolysis Bullosa
Chiesi Global Rare Diseases, a division within the Chiesi Group dedicated to providing innovative therapies and solutions for individuals grappling with rare diseases, has disclosed that the U.S. Food and Drug Administration (FDA) has granted approval for FILSUVEZ® (birch triterpenes) topical gel. This approval is specifically for the management of partial thickness wounds in individuals aged 6 months and older who are diagnosed with Junctional Epidermolysis Bullosa (JEB) and Dystrophic Epidermolysis Bullosa (DEB). Notably, FILSUVEZ marks a groundbreaking advancement as the inaugural sanctioned treatment for wounds associated with JEB, an uncommon and severe form of Epidermolysis Bullosa characterized by blistering that initiates in infancy. It’s worth mentioning that FILSUVEZ became part of the Chiesi portfolio following the acquisition of Amryt Pharma in January of the previous year.
Epidermolysis Bullosa is an incapacitating genetic skin condition that renders an individual’s skin extremely delicate, making it susceptible to damage even from gentle contact. This rare, persistent, and distressing ailment impacts individuals across all age groups, including infants, children, and adults, causing severe and recurring blistering along with persistent wounds that lead to unbearable pain and restricted mobility. Coping with epidermolysis bullosa involves facing daily hurdles, such as the slow healing of wounds that are prone to infection and undergoing painful dressing changes. FILSUVEZ offers a home-based treatment option, facilitating its incorporation into existing care routines. The application of FILSUVEZ directly onto the wound is part of the regular dressing change procedure.
“At Chiesi Global Rare Diseases, our motivation stems from a commitment to easing the challenges encountered by the rare disease community. We strive to offer groundbreaking therapies and solutions that address significant unmet needs,” expressed Giacomo Chiesi, Head of Chiesi Global Rare Diseases. “We appreciate the backing of individuals living with Epidermolusis Bullosa and their devoted caregivers, enabling us to achieve this noteworthy FDA approval and offer FILSUVEZ as an impactful solution for wound care management.”
Bristol Myers Squibb Adds Premier Radiopharmaceutical Platform with Acquisition of RayzeBio
Bristol Myers Squibb and RayzeBio, Inc. have entered into a definitive merger agreement, where Bristol Myers Squibb will purchase RayzeBio at $62.50 per share in cash, totaling an equity value of roughly $4.1 billion, or $3.6 billion after considering estimated acquired cash. The boards of both companies unanimously approved this transaction.
RayzeBio, a clinical-stage company specializing in radiopharmaceutical therapeutics, holds a leading position in actinium-based RPTs (Radiopharmaceutical Therapies) and maintains a pipeline comprising potentially pioneering drug development programs, aiming primarily at treating solid tumors such as GEP-NETs, small cell lung cancer, hepatocellular carcinoma, and others. There’s a notable demand for more effective treatments in solid tumors, and RPTs offer a precise approach to addressing this need by targeting tumor cells and delivering focused radiation to eliminate cancer cells. Actinium-based RPTs, particularly, exhibit potential advantages over existing therapies due to their high potency and limited radiation range, which could result in heightened efficacy and targeted delivery.
Christopher Boerner, Ph.D., CEO of Bristol Myers Squibb, highlighted that this merger fortifies their oncology portfolio, introducing a unique platform and pipeline, promising substantial growth prospects in the coming years. He emphasized the transformative impact of radiopharmaceutical therapeutics in cancer care and the anticipation of bolstering RayzeBio’s innovative platform through support and expedited development.
Ken Song, M.D., President and CEO of RayzeBio, expressed optimism about the collaboration, citing the persistent need for improved solid tumor treatments and the potential of radiopharmaceutical therapeutics in oncology. He highlighted Bristol Myers Squibb’s established presence and expertise in developing and commercializing oncology treatments as a pivotal factor in this partnership.
RayzeBio’s portfolio includes several programs such as RYZ101 targeting GEP-NETs and ES-SCLC, RYZ801 targeting HCC, and other assets aimed at treating solid tumors. They are in various stages of clinical trials and development, with promising results reported from the ongoing trials.
The acquisition is expected to impact Bristol Myers Squibb’s earnings per share in 2024 but is considered a strategic move for the company’s oncology portfolio. Financing for the acquisition is anticipated to primarily come from new debt issuance, leveraging Bristol Myers Squibb’s financial stability to maintain strong credit ratings and continue investment in growth opportunities, dividends, and share repurchases.
AstraZeneca to Acquire Gracell, Furthering Cell Therapy Ambition Across Oncology and Autoimmune Diseases
AstraZeneca has finalized an agreement to acquire Gracell Biotechnologies Inc., a global biopharmaceutical company in the clinical stage that focuses on innovative cell therapies for cancer and autoimmune diseases. This move aligns with AstraZeneca’s aspirations in cell therapy.
The intended acquisition will bolster AstraZeneca’s expanding portfolio of cell therapies by adding GC012F, a novel clinical-stage autologous chimeric antigen receptor T-cell (CAR-T) therapy utilizing FasTCAR technology, which targets both BCMA and CD19. This therapy holds promise as a potential treatment for multiple myeloma, various hematological malignancies, and autoimmune disorders such as systemic lupus erythematosus (SLE).
Autologous CAR-T involves reprogramming a patient’s immune T cells to combat cells causing diseases, with its manufacturing process being intricate and time-consuming. Gracell’s FasTCAR platform significantly streamlines this manufacturing process, improves T cell fitness, and potentially enhances the efficacy of autologous CAR-T therapy for patients. The future scope of this technology might extend to addressing rare diseases.
Susan Galbraith, Executive Vice President of Oncology R&D at AstraZeneca, stated, “The proposed acquisition of Gracell will complement AstraZeneca’s current capabilities and previous investments in cell therapy, where we’ve made headway in CAR-T and T-cell receptor therapies (TCR-Ts) for solid tumors. GC012F will expedite our strategy in cell therapy for blood-related disorders, aiming to deliver a potential leading treatment using an innovative manufacturing process. Additionally, we aim to explore cell therapy’s potential in resetting the immune response for autoimmune diseases.”
Dr. William Cao, the founder, Chairman, and CEO of Gracell, expressed, “We are eager to collaborate with AstraZeneca to fast-track our mutual objective of making groundbreaking cell therapies available to more patients grappling with debilitating illnesses. By pooling our expertise and resources, we can unlock new avenues in utilizing the Gracell FasTCAR manufacturing platform. We believe this platform has the potential to optimize engineered T cells’ therapeutic characteristics, paving the way for the next generation of autologous cell therapies.”
Post-acquisition, Gracell will function as a wholly owned subsidiary of AstraZeneca, maintaining its operations in both China and the United States.
Innovent Dosed First Participant in Phase 3 Clinical Study (GLORY-2) of Mazdutide (IBI362) Higher Dose 9 mg in Chinese Adults with Obesity
On January 1, 2024, Innovent Biologics, Inc. (Innovent) (HKEX: 01801) reported the successful dosing of the first participant in the Phase 3 clinical trial (GLORY-2). This trial evaluates the higher 9 mg dosage of mazdutide (Innovent R&D Code: IBI362), a dual agonist targeting the glucagon-like peptide 1 receptor (GLP-1R) and glucagon receptor (GCGR), in Chinese adults with obesity. Notably, this marks the fourth extensive Phase 3 clinical study involving mazdutide.
Innovent has secured an exclusive license agreement with Eli Lilly and Company (Lilly) for the development and potential commercialization of mazdutide, in China. Clinical studies have showcased mazdutide’s promising effects, including significant weight loss, improved glucose control, reduced waist circumference, lowered blood lipids and pressure, decreased uric acid levels, liver enzyme improvement, decreased liver fat content, and enhanced insulin sensitivity. Presently, four Phase 3 studies are ongoing, evaluating mazdutide’s impact on Chinese patients with overweight or obesity (GLORY-1 and GLORY-2) and those with type 2 diabetes (DREAM-1 and DREAM-2). These trials aim to further substantiate its efficacy in these patient populations.
GLORY-2 aims to recruit 450 participants who will be randomly assigned to receive either mazdutide 9 mg treatment or a placebo. The trial’s primary endpoints focus on evaluating the percentage change in body weight from the study’s baseline to week 60 and determining the proportion of subjects achieving a body weight reduction of 5% or more from the baseline at week 60. These endpoints serve as key measures to assess the efficacy of mazdutide in managing obesity over the 60-week trial period.
In a Phase 2 study involving Chinese individuals with obesity (BMI ≥ 30 kg/m2) documented under trial NCT04904913, mazdutide at a 9mg dose exhibited promising outcomes. Over a 48-week treatment period, mazdutide demonstrated a noteworthy 18.6% placebo-adjusted average reduction in body weight. Additionally, it contributed to reductions in waist circumference, blood pressure, lipid levels, serum uric acid, transaminase, and liver fat content, indicating multiple metabolic benefits for the participants. Mazdutide’s tolerability was favorable, with an overall safety profile akin to other drugs within the GLP-1 class, and no new safety concerns were identified.
Dr. Lei Qian, Vice President of Clinical Development at Innovent, stated, “Different dosage regimens of mazdutide are suitable for different groups of people with obesity. Mazdutide 9 mg is specifically developed to meet the weight loss needs of people with moderate to severe obesity with a BMI above 30 kg/m2 in China. In a phase 2 study, mazdutide 9 mg showed a more than 18% placebo -adjusted weight loss and multiple cardiovascular and metabolic benefits. In addition, mazdutide 9 mg has simple titration steps and a good safety profile. We are hopeful that mazdutide 9 mg will fully demonstrate its powerful efficacy and good safety in the GLORY-2 study, and bringing a more ideal drug treatment option to patients with moderate to severe obesity, whose current recommended treatment is bariatric surgery.”
China possesses the world’s largest population affected by overweight or obesity, a trend anticipated to escalate further. In 2019, fatalities attributed to overweight and obesity contributed to 11.1% of deaths associated with chronic non-communicable diseases—an alarming rise from 5.7% reported in 1990. This upsurge underlines the escalating health risks posed by obesity-related conditions in China, emphasizing the critical need for effective interventions and management strategies.
Obesity represents a chronic condition demanding sustained management, yet China faces a scarcity of enduringly effective and safe treatments. Globally, several major pharma and biotech companies including Innovent, and others are actively working to develop new therapies to treat Obesity. The anticipated launch of new therapies is expected to immensely improve the lives of the patients affected by obesity.
Zevra Therapeutics Announces Resubmission of Arimoclomol New Drug Application to the US Food and Drug Administration
On December 27, 2023, Zevra Therapeutics, Inc. (NasdaqGS: ZVRA) announced the resubmission of its New Drug Application (NDA) for arimoclomol, an investigational treatment for Niemann-Pick Disease Type C, to the US FDA on December 22, 2023. Zevra anticipates receiving an acknowledgment letter from the FDA confirming the completeness of the resubmission and establishing the PDUFA date within approximately 30 days, following standard NDA review timelines. Zevra expects the NDA to fall under Class II submission, implying an anticipated FDA review period of approximately six months from the submission date.
Zevra is confident it has addressed the FDA’s prior concerns outlined in the complete response letter. This was achieved by providing additional evidence supporting the Niemann-Pick Disease Type C Clinical Severity Scale (NPCCSS) and conducting supplementary studies to further validate the potential mechanism of action. The resubmission incorporates fresh data derived from various sources, including multiple non-clinical studies, comparisons with natural history, real-world data from ongoing early access programs in the U.S. and EU, as well as findings from the four-year open-label extension of the Phase 2/3 clinical trial (NCT02612129). Outcomes from this extended trial indicate that arimoclomol potentially mitigates the long-term progression of NPC.
Arimoclomol underwent assessment in 21 studies encompassing Phase 1, 2, or 3 clinical trials, examining its safety and efficacy. These trials encompassed over 600 subjects, including those with Niemann-Pick Disease Type C, other diseases, and healthy individuals. The pivotal efficacy study specifically targeting NPC was the Phase 2/3 trial (CT-ORZY-NPC-002), a double-blind, placebo-controlled trial involving 50 NPC patients to evaluate the effectiveness of arimoclomol.
Zevra has earned several notable designations from regulatory bodies for Arimoclomol. The U.S. FDA granted it orphan drug designation, Fast Track designation, Breakthrough Therapy designation, and rare pediatric disease designation for NPC. Additionally, the European Medicines Agency (EMA) bestowed orphan medicinal product designation for NPC treatment. Zevra proceeded to resubmit the New Drug Application (NDA) to the FDA in December 2023.
“The Zevra team has worked diligently to deliver a high quality and thorough resubmission of the NDA for arimoclomol following multiple interactions with the FDA and after incorporating direction from the agency,” said Neil McFarlane, President and Chief Executive Officer of Zevra. “We continue to accelerate our launch preparations in anticipation of FDA approval, and believe we are one step closer to getting arimoclomol into the hands of patients who are seeking a treatment.”
“Zevra has engaged with the advocacy community, elevating the patient voice throughout arimoclomol’s development process,” said Daniel Gallo, Ph.D., Zevra’s Senior Vice President of Medical Affairs and Advocacy. “The advocacy community’s input has been instrumental in building awareness of the need for approved treatments that address the unmet needs of individuals and their caregivers living with this debilitating condition.”
Niemann-Pick Disease Type C is an exceptionally rare and progressive genetic disorder leading to fatal neurological complications. It arises from mutations occurring in the NPC1 or NPC2 genes. These genes encode crucial proteins found within lysosomes, vital compartments responsible for lipid transport and metabolism. Mutations in either gene cause a depletion of NPC1 or NPC2 proteins, disrupting lysosomal function. This disruption leads to the buildup of intracellular lipids, potentially resulting in cell death if left untreated.
As per DelveInsight, the diagnosed prevalent cases of Niemann-Pick Disease Type C were estimated to be 787 in the 7MM in 2022, of which 335 of the accounted cases were estimated to be from the US alone, and these cases are expected to increase in the upcoming years. The Gender-specific diagnosed prevalent cases of Niemann–Pick Disease Type C (NPC) were found to be 354 and 433 cases categorized into Males and Females, respectively, in the 7MM in 2022.
Ongoing clinical trials in Niemann-Pick Disease Type C treatment by pharma giants such as Zevra Therapeutics and others are poised to significantly alleviate the burden of this condition. The ongoing clinical trials promise novel insights and potential breakthroughs, offering hope for more effective therapies. By exploring innovative approaches and treatments, pharma giants aim to transform the NPC treatment landscape, providing newfound avenues for managing this challenging disorder and improving patients’ quality of life.
