AstraZeneca’s Newly Occupied Alexion Hits Rock Bottom After Ultomiris (Ravulizumab) Fails to Show Efficacy in Patients with Amyotrophic Lateral Sclerosis

AstraZeneca’s 39 billion USD complete acquisition of Alexion took over just a few months back. Unpleasant news strike hard for their first deal in the rare neurodegenerative disease domain. Alexion focuses on finding medications for rare diseases and has an ongoing clinical trial for Ultomoris (Ravulizumab) to treat the rare disease – Amyotrophic Lateral Sclerosis (ALS). 

ALS is a neurodegenerative neuromuscular disease that can slowly weaken muscles and impair physical function. A progressive loss of motor function subsequently makes a person unable to have voluntary control of their movements. It can leave a person paralyzed for life and even fatal if remain untreated.

Alexion launched the CHAMPION ALS study – a Phase 3, randomized, placebo-controlled, double-blind clinical trial of C5 inhibitor Ultomoris (Ravulizumab) across a range of 382 ALS participants. The study was held in around 90 sites in Europe, Asia, and North America. After the test results came out, there were no significant signs of increased safety and efficacy as expected. So, the Independent Data Monitoring Committee (IDMC) recommended halting the clinical trials for future purposes. The data collected after the study remained constant with no new progressive achievement. Ultomiris was considered the first-in-line treatment and the only long-acting C5 complement inhibitor that inhibits C5 protein in the terminal complement cascade, a part of the body’s immune system. Apart from ALS, Ultomoris is approved for treating rare blood diseases – Paroxysmal Nocturnal Hemoglobinuria (PNH) and atypical Haemolytic Uremic Syndrome (aHUS) and was found to be very effective.

Gianluca Pirozzi, MD, Ph.D., Senior Vice President, Head of Development and Safety, Alexion, said: “We are disappointed by this outcome and what it means for patients with this devastating disease. We would like to thank the entire ALS community as well as investigators and healthcare professionals who dedicated their time and expertise to this trial. We continue to be confident in the potential of targeting C5 for complement-driven diseases and remain fully committed to our efforts to serve the rare disease community.”  

USFDA Grants Clinical Trial Approval to Beijing HebaBiz Biotech’s Siroquine (JP001) – An Innovative Anti-Cancer Drug

Beijing HebaBiz Biotech’s Siroquine (JP001) drug was granted clinical trial approval from USFDA. Siroquine is to be tested on patients with newly diagnosed glioblastoma (GBM), an aggressive type of cancer. It mainly occurs in the brain and spinal cord with diagnostic symptoms like headache, blurred vision, nausea, and seizures. 

HebaBiz Biotech has received a global license for JP001 for anti-tumor indication. The ongoing multicenter, open-label, phase II/III clinical trial study results were positive in overall survival benefit, safety, and efficacy, combined with standard chemoradiotherapy. 

Siroquine is an innovative anti-cancer drug under development based on the Autophagy mechanism. Autophagy is a lysosomal procedure that aids in maintaining cellular homeostasis and cell survival. Now, glioblastoma (GBM) indicates very strong autophagy and is considered a type of tumor that shows resistance to radiotherapy and chemotherapy. Autophagy regulation is the pivot to overcome this resistance of glioblastoma cells. Siroquine (JP001) is developed as a dual autophagy modulator to improve tumor cells’ sensitivity to chemotherapy and radiotherapy. 

Important targets achieved by Siroquine in cancer treatment are- it acts as an anti-cancer sensitizer (originate autophagy, obstruct tumor cell proliferation and increased sensitivity to chemoradiotherapy); increased therapeutic value (curing effects on different classes of cancer – multiple myeloma, sarcoma, glioblastoma lymphangiomyoma, renal cell carcinoma, bladder cancer and a few more); higher efficacy (if given in addition to standard treatment).

The clinical trials for the study of Siroquine will be conducted in Taiwan, the United States, and Mainland China. Until now, six patients have been recruited for the examination, with 4 females and 2 males currently ranging from age 41 to 58 years.

European Commission (EC) Approved Pfizer’s XELJANZ (tofacitinib citrate) for Active Polyarticular Juvenile Idiopathic Arthritis and Juvenile Psoriatic Arthritis

Marketing authorization has been granted to Pfizer’s XELJANZ (tofacitinib citrate) by European Commission (EC) for the treatment of Active Polyarticular Juvenile Idiopathic Arthritis (JIA) and Juvenile Psoriatic Arthritis (PsA) in children of 2 years above and other adolescents. Approval of 2 formulations was granted, one a tablet and the other an oral solution with weight-based dosage. EC also approved treatment from XELJANZ (prolonged-release 11 mg once-daily) tablets in adults experiencing Active Psoriatic Arthritis. This medication was given after children or adult patients demonstrated an inadequate, ineffective, or intolerable response to methotrexate or other therapy with disease-modifying antirheumatic drugs (DMARDs).

Polyarticular Juvenile Idiopathic Arthritis (JIA) is a chronic inflammatory disease of unknown etiology. It is responsible for arthritis in five or more joints in younger children and teenagers within 6 months of experiencing it for the first time. JIA affects both the small joints (hand and feet) and large joints (knees, hips, and ankles). Psoriatic Arthritis (PsA) is arthritis affecting people with an already present skin condition – psoriasis.

A Phase 3 clinical trial study was conducted for 44 weeks with two phases – an 18-week open-label study with 225 patients and a 26-week double-blind, placebo-controlled, randomized study with 173 patients experiencing polyarticular JIA and juvenile PsA. The results met the primary endpoint with a ratio of the occurrence of significantly lower disease flare of 30-31 percent in patients treated with tofacitinib to disease flare of 55 percent with placebo therapy. 

XELJANZ is the first in the league and is currently the only oral JAK inhibitor approved in the European Union for four indications in adults with moderate to severely active rheumatoid arthritis (RA).

Bristol Myers Squibb’s Opdivo (Nivolumab) Receives A Green Signal From FDA for the Adjuvant Treatment of Patients with High-Risk Urothelial Carcinoma

Accelerated approval has been granted to Bristol Myers Squibb’s Opdivo (Nivolumab) by the US Food and Drug Administration based on tumor response rate and duration of response. Nivolumab is indicated for patients experiencing locally advanced or metastatic Urothelial Carcinoma despite prior treatment with neoadjuvant chemotherapy, nodal involvement, or PD-L1 status. 

Urothelial Carcinoma is the most common type of bladder cancer and is highly aggressive compared to other types of cancer, including urinary tract cancer.

A phase 3 clinical trial study – CheckMate 274 was conducted with a dosage of 240 mg every 2 weeks or 480 mg every 4 weeks. This study was under the supervision of the FDA’s Real-Time Oncology Review (RTOR) pilot program whose main goal is to ensure the safety and efficacy of treatments available to patients enrolled in the study. Patients administered with Nivolumab exhibited a 30% decrease in the risk of disease recurrence and death compared with placebo.

Although Nivolumab may cause severe immune-mediated adverse effects such as pneumonitis, colitis, hepatitis, there was almost no adjuvant treatment for bladder cancer. Opdivo becomes the first PD1/L1 drug to treat bladder cancer after surgery.

“At Bristol Myers Squibb, our leading research in immunotherapy has helped transform the way many cancers are treated, and we are continuing to bring these advancements to patients with earlier stages of disease, particularly in challenging cancers with significant unmet need,” was told by Adam Lenkowsky, senior vice president and general manager of U.S. Cardiovascular, Immunology and Oncology at Bristol Myers Squibb.

Volume Status Monitoring Executed by Masimo’s Root Platform With Incorporated PVi (Pleth Variability Index) in Spontaneously Breathing Hemodialysis Patients

A global medical technology production company, Masimo, is now responsible for monitoring volume status and changes in the breathing spontaneity of patients undergoing Hemodialysis by utilizing its Masimo Root platform. It constitutes a robust, expandable patient monitoring and connectivity hub that includes various technological devices and other systems. 

Earlier around 100 studies have indicated that PVi is an effective measure to demonstrate fluid responsiveness in patients. A study was conducted with 60 adult patients enrolled with end-stage renal disease, receiving a routine Hemodialysis (fluid was removed). The PVi (Pleth Variability Index) was measured by the Masimo pulse oximetry sensor attached to a Masimo Root monitor. Data were collected both before and after the Hemodialysis, and changes in the PVi were recorded, in contrast with the fluid removed from the body.

After the study, researchers concluded that a significant change in PVi was observed with increased mean PVi after Hemodialysis and vigorously corresponded with the volume of fluid removed.

PVi provides a continuous noninvasive measure of the relative variability in the photoplethysmograph (pleth) during respiratory cycles that may be used as a dynamic indicator of fluid responsiveness in select populations of mechanically ventilated adult patients. – Masimo