There is no news on why Biogen made the decision, although XPO1 inhibitors can have substantial side effects commensurate with their anticancer effects, including myelosuppression, gastrointestinal effects, and low sodium in the blood. The move depletes Biogen’s pipeline in ALS, one of its major research areas, and comes just a few months after tofersen, the company’s lead candidate for the disease, failed a phase III trial. Aside from tofersen, Biogen’s only other clinical-stage ALS candidate is BIIB105, a phase I antisense drug developed in collaboration with Ionis that targets ataxin-2.
AbbVie’s Immunological Drug Skyrizi Clinches Third Indication Nod
The FDA has granted AbbVie’s Skyrizi (risakizumab-rzaa) the first approval in the specialized interleukin-23 inhibitor category for Crohn’s disease. Skyrizi is now approved for use in individuals with moderate to severe active Crohn’s disease. The drug inhibits IL-23 by attaching to its p19 subunit. IL-23 is involved in the inflammatory processes seen in many chronic immune-mediated diseases. At weeks 0, 4, and 8, patients receive 600 mg of the drug through IV for at least an hour, followed by 360 mg every 8 weeks via self-administered subcutaneous injection.
The FDA’s decision is based on favorable findings from two induction (ADVANCE and MOTIVATE) and one maintenance (FORTIFY) clinical study in which Skyrizi demonstrated the ability to improve endoscopic response or a reduction of more than 50% from baseline Simple Endoscopic Score in CD. Among other positive outcomes, the drug provided a better clinical remission response than the placebo, as judged by the Crohn’s Disease Activity Index. The FDA is also reviewing a 180 mg self-administered subcutaneous injection as a maintenance dose alternative, and a decision is expected soon.
In addition to Crohn’s disease, Skyrizi is approved by the FDA for use on moderate to severe plaque psoriasis in adults who qualify for systemic therapy or phototherapy and in active psoriatic arthritis adults. The latest FDA approval for Crohn’s disease is excellent news for AbbVie, which is undoubtedly looking for a new lead product after the success of Humira.
FDA Grants Fast Track Designation to Dianhydrogalactitol for Newly Diagnosed Glioblastoma
Kintara Therapeutics is focused on developing new solid tumor cancer therapies. The organization announced that the United States Food and Drug Administration (FDA) had granted Fast Track Designation to Kintara’s VAL-083 for treating patients suffering from newly-diagnosed unmethylated glioblastoma (GBM).
VAL-083 is a “first-in-class,” small-molecule chemo-therapeutic with a novel mechanism of action that has demonstrated clinical activity against a broad category of tumors, including the ovarian, central nervous system, and other solid tumors (for instance, head and neck cancer, non-small cell lung cancer, bladder cancer) in the United States clinical trials endorsed by the National Cancer Institute. Based on internal research programs and the prior NCI-supported clinical studies, Kintara is progressing VAL-083 in the Global Coalition for Adaptive Research registrational phase II/III clinical trial titled Glioblastoma Adaptive Global Innovative Learning Environment (GBM AGILE) study to support the development and commercialization of VAL-083 in GBM.
Fast Track is a method designed to ease the development and expedite the review of drugs to treat severe conditions and fill unmet medical needs. Some of the significant benefits of Fast Track Designation include:
- Boosted access to the FDA, including opportunities for more meetings and consultations throughout the remaining developmental process of VAL-083.
- Drugs with Fast Track Designation are applicable to apply for Accelerated Approval and Priority Review at the time of the submission for New Drug Application.
- FTD also permits for ‘rolling review,’ whereby Kintara may submit completed sections of the VAL-083 NDA as they become accessible, rather than at the end of development.
Robert E. Hoffman, President and CEO of Kintara, added, “We think Fast Track Designation is indicative of VAL-083’s potential to improve results for patients with GBM, the most aggressive form of brain cancer“.
Sierra Oncology Submits NDA for Momelotinib to FDA
Sierra Oncology announced that the company had submitted a New Drug Application (NDA) to the US Food and Drug Administration (FDA) for momelotinib inhibitor in development for the treatment of myelofibrosis.
Momelotinib is a dynamic and orally bioavailable ACVR1/ALK2, JAK1, and JAK2 inhibitor which is under investigation for the treatment of myelofibrosis in symptomatic and anemic patients who are previously treated with an approved Janus kinase inhibitors inhibitor. More than 1,200 patients have received momelotinib since clinical studies started in 2009, including around 1,000 patients treated for myelofibrosis, several of whom remain in treatment for 12 years. Momelotinib is the first and only Janus kinase inhibitor to show positive data for symptoms, splenic response, and anemia.
MOMENTUM is a randomized and double-blind Phase 3 clinical trial of momelotinib versus danazol in patients suffering from myelofibrosis who were symptomatic and anemic and had been previously treated with an FDA-approved JAK inhibitor. The research was designed to assess the safety & efficacy of momelotinib for the treatment and reduction of the key hallmarks of the disease: symptoms, blood transfusions, and splenomegaly.
The primary endpoint of the research is a total symptom score reduction of more than 50 percent over 28 days immediately before the end of Week 24 compared to the baseline total symptom score, using the Myelofibrosis Symptom Assessment Form. Secondary endpoints included Transfusion Independence rate for more than 12 weeks immediately before Week 24 with hemoglobin levels ≥ 8 g/dL and Splenic Response Rate based on splenic volume reduction of more than 35 percent at Week 24. The study admitted 195 patients based on 180 patients across 21 countries.
NICE Backs Astellas’ Oral Therapy Evrenzo for Anemia in Kidney Disease
The NHS has recommended the Astellas’ oral HIF-PH inhibitor Evrenzo for the treatment of anemia in chronic kidney disease (CKD). Evrenzo (roxadustat) becomes the first therapy in the class to be recommended as an oral alternative to treatment with injectable iron supplements or erythropoietin-based therapies for symptomatic anemia associated with CKD. Currently, other players such as Otsuka, GlaxoSmithKline, and others are awaiting approval from the regulatory authority for their therapies.
Evrenzo activates the body’s natural response to reduced oxygen levels in the blood, increasing red blood cell production. In his statement, Timir Patel, medical director at Astellas UK & Ireland, has said that the coverage decision from the National Institute for Health and Care Excellence (NICE) “is a vote of confidence in roxadustat as a cost-effective oral treatment option. The development of therapy Evrenzo was initiated by FibroGen and later it was licensed to Astellas in Europe. Last year, FDA rejected FibroGen’s marketing application, which forced the companies to explore new opportuinite outside of the U.S. with novel oral therapy. The authorities in the UK and EU has approved the therapy last year.
Astellas’s Evrenzo has high prospects in the Anemia in Kidney Disease Market, as other closest rivals, GlaxoSmithKline’s daprodustat and Otsuka/Akebia Therapeutics’ vadadustat are expected to undergo the regulatory approval process. In England and Wales, nearly 75,000 people are estimated to be affected by anemia associated with CKD. The NICE backing to Evrenzo is expected to improve the treatment scenario.
Roche’s Crenezumab Fails in Clinical Trial for Alzheimer’s Disease
Roche and AC Immune have announced that their anticipated drug for Alzheimer’s Disease, crenezumab, failed to “meaningfully” slow or prevent the progression of the disease. The data presented did not demonstrate a statistically significant clinical benefit in cognitively unimpaired people who carry a specific genetic mutation which lead to the early onset of Alzheimer’s disease.
As per the phase 2 Alzheimer’s Prevention Initiative (API) Autosomal Dominant Alzheimer’s Disease (ADAD) Colombia trial (NCT01998841) data, the therapy did not meet the co-primary endpoints assessing the rate of change in cognitive abilities or episodic memory function in cognitively unimpaired persons who are at risk for Alzheimer disease. The API ADAD trial was a prospective, randomized, double-blind, parallel-group study that enrolled 252 cognitively unimpaired individuals and carry the PSEN1 E280A autosomal dominant mutation.
Alzheimer’s disease is a debilitating neurological disorder that gradually erodes memory and cognitive abilities. It is observed that nearly 6 million people were living with Alzheimer’s disease in 2020 in the US. Despite high burden there are is a significant unment need in the therapeutics segment.
