Renal cell carcinoma (RCC) stands out as the predominant form of kidney cancer in adults, with over 431,000 new cases and 179,000 fatalities reported globally annually. The prevalence of RCC is roughly twice as high in men compared to women, and the highest incidence rates are observed in North America and Europe. Notably, at the time of diagnosis, around 30% of patients exhibit advanced or metastatic stages of RCC.
AIRSUPRA Now Available as the First and Only FDA-approved Anti-inflammatory Rescue Option for Asthma
AstraZeneca has officially launched AIRSUPRA® (albuterol/budesonide) in the United States through prescription. The FDA approved AIRSUPRA in January 2023 for its use in treating or preventing asthma symptoms on an as-needed basis, as well as aiding in the prevention of sudden, severe breathing difficulties (asthma attacks) in individuals aged 18 and above. AIRSUPRA combines a short-acting beta2-agonist (SABA) to relax the airway smooth muscles and an inhaled corticosteroid (ICS) to reduce lung inflammation. The approval of AIRSUPRA was based on findings from two Phase III trials, MANDALA and DENALI. In the MANDALA trial, AIRSUPRA demonstrated superiority over albuterol in reducing the risk of severe asthma exacerbations in patients with moderate to severe asthma. In the DENALI trial, AIRSUPRA exhibited a similar onset of bronchodilation compared to albuterol in patients with mild to moderate asthma.
The strategy for addressing asthma symptoms using rescue methods has evolved. The 2023 Global Initiative for Asthma (GINA) report advocates for a revised rescue approach that simultaneously addresses both symptoms and inflammation. The use of a combined SABA/ICS is now suggested as a rescue option for adults with asthma, irrespective of their ongoing ICS maintenance medication. GINA underscores that the shift in the recommended rescue strategy is primarily influenced by the risks associated with relying solely on SABA for asthma treatment. In the United States, AIRSUPRA stands out as the sole FDA-approved, on-demand SABA/ICS asthma rescue, designed to effectively manage both symptoms and inflammation.
Priya Bansal MD, Physician and CEO of the Asthma and Allergy Wellness Center, expressed that for more than five decades, the medical field has relied on SABA-only rescue, overlooking the inflammatory aspect of asthma. With the introduction of AIRSUPRA, there is now an additional rescue option for patients, particularly those undergoing maintenance therapy, to effectively handle breakthrough symptoms. The MANDALA study has illustrated the advantages for such patients, showing how an as-needed anti-inflammatory rescue can treat their symptoms and contribute to attack prevention, even when they are already on maintenance therapy containing ICS.
AstraZeneca’s Voydeya Receives First-ever Regulatory Approval in Japan for Adults with PNH
Voydeya (danicopan) has received approval in Japan for treating paroxysmal nocturnal hemoglobinuria (PNH). In Japan, it is prescribed in combination with C5 inhibitor therapy for patients who have not responded adequately to such inhibitors. Voydeya, a first-of-its-kind oral Factor D inhibitor, has been developed as an adjunct to the established standard-of-care Ultomiris or Soliris. This addresses the specific needs of a subset of PNH patients (approximately 10-20%) who undergo clinically significant extravascular hemolysis (EVH) despite treatment with a C5 inhibitor. The Japanese Ministry of Health, Labour and Welfare (MHLW) granted approval based on positive outcomes from the pivotal ALPHA Phase III trial. The results from the 12-week primary assessment period of the trial were published in The Lancet Haematology.
PNH is a rare and serious hematologic condition marked by the breakdown of red blood cells within blood vessels, referred to as intravascular hemolysis (IVH). Additionally, it involves the activation of white blood cells and platelets, which can lead to thrombosis (formation of blood clots), potentially causing organ damage and premature death. According to DelveInsight’s estimates, In 2023, the total diagnosed prevalent cases of PNH in the US were ~6,100 cases which is anticipated to increase by 2034 at a moderate CAGR during the study period 2024-2034. Among the 7MM countries, the US comprised ~49% of the total diagnosed prevalent cases of PNH in 2023.
The Phase III ALPHA trial assessed the effectiveness and safety of Voydeya when used in conjunction with Ultomiris or Soliris for patients with paroxysmal nocturnal hemoglobinuria (PNH) who had experienced clinically significant extravascular hemolysis (EVH). This was defined as a hemoglobin level of 9.5 g/dL or lower and absolute reticulocyte count levels of 120×10^9/L or higher. The results demonstrated that Voydeya successfully achieved the primary outcome of altering hemoglobin levels from baseline to week 12, as well as meeting all critical secondary endpoints, such as avoiding transfusions and influencing the change in Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-Fatigue) score.
Voydeya has received Breakthrough Therapy designation from the FDA and has been granted PRIority MEdicines (PRIME) status by the European Medicines Agency. Additionally, it has obtained Orphan Drug Designation in the US, EU, and Japan for addressing PNH. The regulatory submissions for Voydeya are presently undergoing assessment with various global health authorities.
GC Biopharma’s Sanfilippo Syndrome (Type A) Treatment Received Orphan Drug Designation (ODD) From the European Medicines Agency (EMA)
GC Biopharma Corp. (006280.KS) announced on January 22, 2024, that the European Medicines Agency (EMA) has granted Orphan Drug Designation (ODD) to its therapy, GC1130A. GC1130A is an intracerebroventricular (ICV) Enzyme Replacement Therapy (ERT) candidate. This therapy is specifically tailored for Sanfilippo Syndrome type A (mucopolysaccharidosis type IIIA) treatment and has been developed in partnership with Novel Pharma.
Since 2020, GC Biopharma and Novel Pharma have joined forces in the collaborative development of GC1130A. Leveraging proprietary recombinant protein manufacturing technology, GC Biopharma has skillfully formulated GC1130A to be compatible with cerebrospinal fluid at high protein concentrations. Notably, Novel Pharma, a biotech company renowned for its expertise in rare disease drug development, has been a valuable partner in this venture, operating in Korea.
Having previously attained significant milestones with Rare Pediatric Disease designation (RPDD) and Orphan Drug Designation (ODD) from the U.S. FDA in January 2023, GC Biopharma’s GC1130A now achieves another notable accomplishment with its recent approval in Europe and holds the potential to immensely influence the Sanfilippo Syndrome (Type A) therapeutics market landscape.
“This EMA designation further underlines the potentials of our collaborative pipeline in addressing the disease pathology in upcoming clinical trials.”, said GC Biopharma and added that it will be “committing to expeditiously advancing into clinical trials, acknowledging the urgent, unmet medical needs of Sanfilippo Syndrome patients.”
Sanfilippo Syndrome, specifically type A, is a genetic disorder characterized by the accumulation of Heparan sulfate, causing damage to the central nervous system and resulting in progressive neurodegeneration, particularly in the pediatric population. Individuals with MPS IIIA typically face a life expectancy of around 15 years, and currently, there are no approved therapies for this condition.
In preclinical studies, GC1130A has shown promising outcomes, demonstrating both safety and efficacy. It has exhibited the ability to eliminate Heparan sulfate and restore brain function, offering a potential breakthrough in addressing the challenges associated with Sanfilippo Syndrome type A. Given the absence of approved therapies, the advancements in GC1130A present a hopeful prospect for improving the quality of life and extending the lifespan of individuals affected by MPS IIIA. Ongoing research and clinical developments aim to further validate these positive findings and pave the way for a much-needed treatment option for this rare genetic disorder.
Sanfilippo Syndrome poses a substantial burden on individuals affected by its debilitating consequences, particularly in the absence of approved therapies. The progressive neurodegeneration in pediatric patients, coupled with a limited life expectancy of around 15 years, underscores the urgent need for effective treatments. Companies like GC Biopharma, in collaboration with partners such as Novel Pharma, are playing a crucial role in overcoming these unmet needs. Through dedicated research and development efforts, utilizing innovative technologies and approaches, they are striving to bring forth potential breakthroughs like GC1130A. These endeavors not only offer hope to patients and their families but also signify a collective commitment to addressing the challenges posed by rare genetic disorders like Sanfilippo Syndrome, ultimately working towards enhancing the quality of life and expanding treatment options for those affected.
NRx Pharma Announces FDA Clearance of its Investigational New Drug (IND) Application for NRX-101 in the Treatment of Complicated Urinary Tract Infections
On December 18, 2023, NRx Pharmaceuticals, Inc. (Nasdaq: NRXP), a clinical-stage biopharmaceutical company, disclosed that the US Food and Drug Administration (FDA) granted clearance for its Investigational New Drug Application (IND) regarding the use of NRX-101. NRX-101 is the company’s patented combination of D-cycloserine and lurasidone, intended for the treatment of complicated Urinary Tract Infections (cUTI).
As previously stated, the company envisions the highest value for this program within an independent entity solely focused on advancing and bringing NRX-101 for complicated Urinary Tract Infections (cUTI) to market. Given the completion of the manufacturing phase, the attainment of Composition of Matter patent protection, and possession of a commercial-grade drug product, no additional research and development investment is anticipated before entering clinical trials. Consequently, the company is in the process of formulating plans to establish a new company, mirroring the planned spin-out of Hope Therapeutics for the development of NRX-100 (IV Ketamine) targeting suicidal depression. In this endeavor, NRx, current shareholders (via a share dividend), and prospective investors will collectively hold ownership in the new company.
“Complicated Urinary Tract Infections afflict approximately 3 million Americans each year, and pathogens have become increasingly resistant to commonly used antibiotics. New treatment options are urgently needed” stated Jonathan Javitt, MD MPH, Founder and Chief Scientist of NRx Pharmaceuticals. “The D-cycloserine (DCS) component of NRX-101 is well known as an antibiotic and is excreted unmetabolized in the urine. However, the NMDA-antagonist effects of DCS led to its disuse in the United States, while it has remained a widely used anti-tuberculosis agent by the World Health Organization. NRx’s patented discovery that combining DCS with small amounts of lurasidone counters the CNS side effects potentially and renders NRX-101 an important, patented antibiotic, just at a time when Americans are increasingly facing intravenous antibiotic therapy and even hospitalization and death from pathogens that were readily controlled a generation ago. This mission is personal to me, in that I have lost two close friends, one the father of a founding investor, to sepsis from urinary infections that were readily controlled a generation ago.”
NRx has appointed Michael Manyak, MD, as the Lead Clinical Advisor for this initiative. Dr. Manyak is a renowned urologist with international recognition, having received training at prestigious universities and the US National Institutes of Health. His recent roles include serving as the Global Medical Affairs Director for the GlaxoSmithKline urology franchise and as the Chief Medical Advisor for Crisis Response at Accenture. In addition, he holds the position of Adjunct Professor of Urology and Engineering and has previously been a Professor of Immunology, Microbiology, and Tropical Medicine at The George Washington University (GWU). Furthermore, he is affiliated with the Baylor College of Medicine National School of Tropical Medicine.
“At a time when routine use of standard antibiotics demonstrates increasing resistance and failure to control urinary tract infections, I believe it is vital to advance safe, oral antibiotics for complicated UTI that have the potential to avoid the need for intravenous therapy, to keep patients out of the hospital, and to save lives,” said Dr. Manyak. “I look forward to learning whether the efficacy we demonstrated for NRX-101 in the laboratory against some of the most resistant bacteria can be replicated in patients.”
The company is currently anticipating the FDA’s response to its request for Qualified Infectious Disease Product (QIDP) designation, with the expectation that the response will be received next month.
NRx Pharmaceuticals plays a pivotal role in advancing the treatment landscape for Complicated Urinary Tract Infections (cUTI). The efforts of NRx Pharmaceuticals, with their focus on research, development, and strategic partnerships, contribute significantly to addressing unmet medical needs and improving treatment options for patients with Complicated Urinary Tract Infections. This dedication is crucial in advancing medical science and providing innovative solutions to improve public health outcomes.
Kyverna Therapeutics Granted FDA Fast Track Designation for KYV-101 in the Treatment of Patients With Refractory Progressive Multiple Sclerosis
Kyverna Therapeutics, Inc. (Kyverna) disclosed on January 19, 2024, that its autologous, fully human CD19 chimeric antigen receptor (CAR) T-cell product candidate, KYV-101, has been granted fast-track designation by the U.S. Food and Drug Administration (FDA) for the treatment of multiple sclerosis (MS).
CAR T-cell therapy entails the alteration of a patient’s T cells to identify and eliminate B cells within the patient’s system. Kyverna’s CD19 CAR T-cell therapy, known as KYV-101, is designed to precisely target CD19, a protein present on the surface of B cells that plays a role in numerous autoimmune diseases. The CAR featured in KYV-101 was developed by the National Institutes of Health (NIH) with the aim of enhancing tolerability. It underwent testing in a Phase 1 trial involving 20 patients in the field of oncology, and the outcomes of this trial were subsequently published by the NIH in Nature Medicine. Kyverna intends to pursue further applications for KYV-101 and advance a strong pipeline of potential immunotherapy products to address unmet medical needs in the realm of autoimmune diseases.
Kyverna is presently engaged in two trials involving KYV-101, focusing on patients with lupus nephritis—an autoimmune condition where over half of the patients fail to attain a complete response with existing therapies, putting them at risk of kidney failure. Furthermore, Kyverna is preparing additional clinical trials for KYV-101, targeting systemic sclerosis, myasthenia gravis, and multiple sclerosis. The distinctive characteristics of KYV-101 are viewed as pivotal for the potential success of CAR T cells in the realm of autoimmune disease therapies.
“We appreciate the FDA’s support to accelerate the development of potentially life-changing CAR T-cell therapies that could greatly benefit patients living with severe and debilitating neurological autoimmune diseases,” said Peter Maag, Ph.D., chief executive officer of Kyverna. “This marks another important milestone in our endeavor to change the treatment paradigm with KYV-101.”
Multiple sclerosis stands as a persistent neurodegenerative autoimmune ailment, impacting over 2.8 million individuals globally. Predominantly affecting women and those of Northern European descent, Multiple sclerosis is also linked to specific environmental and genetic factors. This complex condition manifests in a spectrum of symptoms, including blurred vision, slurred speech, tremors, numbness, profound fatigue, cognitive difficulties, and, in severe instances, the loss of mobility.
Patients with Multiple sclerosis face significant challenges, and the current array of disease-modifying treatments primarily aims to mitigate the frequency of relapses and postpone the progression of disability. Despite these efforts, Multiple sclerosis remains an enduring condition that tends to worsen progressively for the majority of individuals affected. Addressing the intricate nature of Multiple sclerosis requires a comprehensive approach that extends beyond the existing treatment paradigm, underscoring the urgent need for innovative therapeutic interventions to enhance the quality of life for those grappling with this debilitating autoimmune disease.
In the dynamic landscape of the Multiple Sclerosis (MS) market, pharmaceutical giants, including Kyverna Therapeutics, have emerged as key players in addressing the unmet needs of patients. By pioneering innovative therapies, these industry leaders are reshaping the treatment paradigm for Multiple sclerosis, offering novel approaches that go beyond the limitations of current disease-modifying treatments. Kyverna Therapeutics, among others, is at the forefront of developing groundbreaking solutions. Through such advancements, pharmaceutical giants are not only working to alleviate symptoms but also striving to transform the trajectory of Multiple sclerosis, providing hope for improved outcomes and enhanced quality of life for those affected by this challenging autoimmune disease.
