Zealand Pharma Announces the Positive Topline Results from its Phase III trial of Glepaglutide
Zealand Pharma A/S, a biotech company specializing in peptide-based medicines, announced positive topline results from its phase III trial of glepaglutide. In the evenly randomized double-blind trial, 106 patients with short-bowel syndrome (SBS) who also had an intestinal failure and were dependent on parenteral support (PS) at least three days per week received treatment with 10mg glepaglutide once or twice weekly or a placebo.
In the EASE 1 phase III trial, glepaglutide, a long-acting GLP-2 analog, was found to meet the primary endpoint when administered twice weekly subcutaneously via auto-injector to SBS patients. The total weekly volume of parenteral support was statistically significantly lower at 24 weeks compared to placebo (p=0.0039). 66% of patients in the twice-weekly group had a clinically meaningful response.
Once-weekly glepaglutide delivery resulted in a numerical reduction in weekly parenteral support, but this was not statistically significant, and nine participants treated with glepaglutide were weaned from parenteral support and achieved enteral autonomy.
At the end of the 24 weeks, the average reduction in parenteral support from baseline was 5.13 liters/week in patients receiving twice-weekly glepaglutide and 3.13 liters/week in patients receiving once-weekly glepaglutide. The placebo treatment resulted in a 2.85 liter/week reduction in parenteral support.
“We are extremely pleased with the results of the Phase III EASE 1 trial,” said David Kendall, M.D., Chief Medical Officer of Zealand Pharma. “In EASE 1, glepaglutide significantly reduced the volume of parenteral support required compared to placebo when administered to patients with SBS and intestinal failure. We are particularly encouraged that a number of patients treated with glepaglutide were able to significantly reduce the burden of parenteral support – both reducing the number of days and completely eliminating the need for parenteral support in a substantial number of patients. We believe the outcome of this trial supports the potential of glepaglutide as an effective treatment for people living with SBS and intestinal failure and can reduce the burden of both parenteral support and daily dosing of GLP-2 treatment. We look forward to seeing the results of the ongoing EASE 2 and 3 long term extension trials and engaging with the regulatory authorities as we plan for submission of our NDA.”
An EASE 4 phase IIIb trial is also planned to evaluate glepaglutide’s long-term effects on intestinal fluid and energy uptake.
FDA Approves Amylyx’s ALS Drug Relyvrio
Amylyx’s amyotrophic lateral sclerosis (ALS) therapy Relyvrio was approved by the FDA, following not one but two advisory committee meetings that reached opposing conclusions about the drug. Relyvrio (sodium phenylbutyrate and taurursodiol) is the first new therapy option for ALS, also known as motor neuron disease (MND) since the FDA approved Mitsubishi Tanabe Pharma’s intravenous Radicava (edaravone) in 2017. This year, an oral version of edaravone was approved.
Relyvrio is a powder that is mixed with water and administered through a feeding tube. It was approved based on the phase II CENTAUR trial in patients with fast-progressing ALS, which demonstrated a 25% slower decline in physical abilities such as walking, speaking, and swallowing than participants given a placebo.
An open-label extension revealed that ALS patients had approximately six more months before being hospitalized, requiring a ventilator, or dying compared to the control group, and patients who continued taking the drug lived approximately ten months longer, according to Amylyx. In March, the first advisory committee agreed with the FDA reviewer’s assessment that there were concerns about Relyvrio’s efficacy and that it would be better to wait for the results of a larger study, which is now expected to be completed in 2024.
Following the six-to-four vote not to recommend approval, ALS patient groups argued strongly that it would be better for patients with a limited lifespan to take a chance on a new drug that appears to be safe, even if it is later found to be ineffective. Faced with the backlash, the FDA convened another advisory committee meeting earlier this month, and this time, despite emotional pleas from patients and doctors, the vote went the other way by a seven-to-two margin.
Novo Nordisk and Ventus Therapeutics Signs USD 70 Million Licencing Deal for NASH Drug
Ventus Therapeutics announced that the company has entered into a worldwide license agreement with the firm Novo Nordisk A/S to develop and commercialize drugs from Ventus’ portfolio of peripherally-restricted NLRP3 inhibitors.
“This is an important association for Ventus that confirms our structural biology capabilities to develop highly differentiated molecules with novel chemical structures,” added Marcelo Bigal, M.D., Ph.D., President, and CEO of Ventus. “We trust that Novo Nordisk is the ideal partner to forward our lead NLRP3 program in a broad range of systemic therapeutic areas in which they have a strong expertise, such as cardio-metabolic disorders.”
Under the terms and conditions of the agreement, Novo Nordisk will make an upfront payment of $70 million in cash to Ventus and offer research and development funding. Additionally, Ventus will be eligible to receive up to an additional $633 million in potential clinical, regulatory, and commercial milestones and tiered royalties.
In exchange, Novo Nordisk will receive exclusive global rights to develop and commercialize Ventus’ lead NLRP3 inhibitor program for various diseases, including non-alcoholic steatohepatitis hepatitis, chronic kidney disease (CKD), and other cardio-metabolic diseases.
Ventus retains the right to develop NLRP3 inhibitors for certain systemic disorders, including inflammatory and respiratory diseases. In addition, Ventus has worldwide rights to the company’s specific brain-penetrant NLRP3 inhibitor program.
“NLRP3 is a biologically significant target with potential across a number of liver, kidney, and cardio-metabolic diseases,” said Karin Conde-Knape, Senior Vice President, Global Drug Discovery at Novo Nordisk. “Ventus has advanced a highly differentiated NLRP3 inhibitor program with best properties and compelling pre-clinical results. We are delighted to partner with Ventus to advance this program to provide meaningful clinical benefit to patients within a broad range of disorders.”
FDA Approves Futibatinib for FGFR2+ Cholangiocarcinoma
The Food and Drug Administration (FDA) approved fibroblast growth factor receptor (FGFR) inhibitor futibatinib (TAS-120) for adult patients suffering with unresectable, locally advanced, or metastatic intrahepatic cholangiocarcinoma with FGFR2 gene fusions or other rearrangements that have been previously treated.
This accelerated approval was based on efficacy results from the open-label, single-arm phase 1/2 TAS-120-101 trial. The trial enrolled 103 patients with unresectable, locally advanced, or metastatic intrahepatic cholangiocarcinoma with an FGFR2 gene fusion or another rearrangement who had previously been treated with at least one systemic gemcitabine and platinum-based chemotherapy. Patients were treated with 20 mg futibatinib orally, once daily, until either disease progression or unacceptable toxicity. The primary efficiency outcomes were objective response rate and duration or response.
The objective response rate was 42%, with all responses being partial. The median duration of response was approximately 9.7 months.
The most common adverse events occurring in approximately ≥20% of patients were nail toxicity, musculoskeletal pain, constipation, diarrhea, fatigue, dry mouth, alopecia, stomatitis, abdominal pain, dry skin, arthralgia, dysgeusia, dry eye disease, nausea, decreased appetite, urinary tract infection, palmar-plantar erythrodysesthesia syndrome, and vomiting.
Sarepta Files Duchenne Muscular Dystrophy Gene Therapy for FDA Approval
On September 29, 2022, Sarepta Therapeutics (NASDAQ:SRPT) announced that it had submitted a Biologics License Application (BLA) to the US FDA for the accelerated approval of SRP-9001 (delandistrogene moxeparvovec). Sarepta’s SRP-9001 is an investigational gene therapy designed to treat Duchenne Muscular Dystrophy (DMD. Sarepta is developing the therapy in partnership with Roche.
The therapy is intended to deliver SRP-9001 to muscle tissue for the targeted production of functional components of dystrophin. Sarepta has proposed its fully-enrolled study EMBARK (Study SRP-9001-301) as the post-marketing confirmatory study to support the accelerated approval.
Earlier in July 2020, FDA granted Fast Track designation to SRP-9001. Moreover, the SRP-9001 has also been granted Rare Pediatric Disease (RPD) designation in the United States and Orphan Drug status in the United States, the European Union, Switzerland, and Japan.
Duchenne Muscular Dystrophy is a rare neuromuscular genetic disease that leads to progressive muscle degeneration and affects about one in every 3,500-5,000 newborns worldwide. DMD occurs due to a change or mutation in the gene that encodes instructions for dystrophin. Apart from Sarepta, globally, several other key players are actively working in the Duchenne Muscular Dystrophy therapeutics market. The approval and the launch of emerging therapies are expected to improve the Duchenne Muscular Dystrophy treatment scenario in the coming years immensely.
Biogen and Eisai’s Lcanemab Aces in Phase III Alzheimer’s Study
On SEPTEMBER 27, 2022, Eisai Co. and Biogen Inc. disclosed positive topline results from the Phase 3 confirmatory Clarity AD clinical trial of lecanemab (development code: BAN2401). Lecanemab is an investigational anti-amyloid beta (Aβ) protofibril antibody designed to treat mild cognitive impairment (MCI) due to Alzheimer’s disease (AD) and mild AD (collectively known as early AD) with confirmed presence of amyloid pathology in the brain. Clarity AD was a global confirmatory Phase 3 placebo-controlled, double-blind, parallel-group, randomized study in 1,795 people with early AD.
As per the statement released by Biogen and Eisai, Lecanemab met the primary endpoint (CDR-SB: Clinical Dementia Rating-Sum of Boxes*) and all key secondary endpoints with favorably significant outcomes. Eisai is further looking forward to discussing the key details from the trials with regulatory authorities in the U.S., Japan, and Europe. The company is intended to file for traditional approval in the US and for marketing authorization applications in Japan and Europe by the end of Eisai’s FY2022, which ends March 31, 2023. Moreover, the Eisai is set to present the Clarity AD study results at the Clinical Trials on Alzheimer’s Congress (CTAD) on November 29, 2022, and publish the findings in a peer-reviewed medical journal.
In 2022, an estimated 5.4 million Americans aged 54 and older will be living with Alzheimer’s disease. Seventy-three percent of affected people are age 74 or older. Almost two-thirds of Americans with the disease are women. According to the Alzheimer’s Association, about 5.4 million Americans aged 54 and older will live with Alzheimer’s disease in the United States in 2022. Moreover, almost two-thirds of people in the US with Alzheimer’s are women. The positive result of the Lcanemab raises high hope for better treatment outcomes for Alzheimer’s patients in the coming years.