Maintains Buy rating
Monday, September 16, 2024
Biden: 'Secret Service 'needs more help' after Trump targeted in apparent assassination attempt'
President Biden says the Secret Service 'needs more help' after Trump targeted in apparent assassination attempt
President Biden says the Secret Service 'needs more help' after Trump targeted in apparent assassination attempt.
[That's IT??]
Zentalis: FDA Lifted Partial Clinical Hold
On track to present data from key clinical studies of azenosertib in the fourth quarter of 2024
Exact Sciences Presents Data on Advancement in Blood-based Colorectal Cancer Screening
Data presented show sensitivities of 88% for colorectal cancer and 31% for advanced precancerous lesions at 90% specificity
Scientific insights reflect Exact Sciences’ commitment to closing the screening gap through innovation
Results shared alongside evidence supporting multi-cancer early detection approach
5 Late-Stage mRNA Vaccines to Watch
The potential of mRNA vaccines was established during the COVID-19 pandemic. Now, a new wave of candidates could soon hit the market for cancer, influenza and more.
The arrival of the COVID-19 pandemic heralded an unprecedented period for the pharmaceutical industry, with vaccines progressing from R&D to worldwide rollout in record time and garnering record-breaking profits for developers. The FDA approval of the mRNA vaccines themselves was also a landmark event, acting as a proof of concept and ushering in this new class of treatments.
“COVID-19 accelerated the timelines of the mRNA pipeline, opening the aperture for the companies to start expanding more broadly into other infectious diseases and then to continue to advance the non-infectious disease part of their mRNA pipelines,” said Jennifer Heller, a partner at McKinsey & Company, which recently published a report on innovation in vaccine development.
This is what happened for Moderna, which recently followed its COVID-19 vaccine with the FDA approval of a respiratory syncytial virus (RSV) vaccine.
The global mRNA therapeutics market size is expected to reach $68 billion by 2030, according to Statista. Within the overall vaccine pipeline, Heller told BioSpace that mRNA technology is disproportionately represented when compared to other technologies, particularly in Phase I trials.
One advantage for mRNA developers is that they can rapidly develop a potential product, as happened during the pandemic. This means that the growth in mRNA vaccines at the early stage of the pipeline could soon be seen later on. It could also establish the technology’s advantage over traditional vaccines, which typically take between five and 10 years to develop and bring to the market.
“The advantage of being able to rapidly create a product that can be tested in the clinic lends itself to accelerated development and that’s been the promise of this technology platform,” Heller said. “I think we’re still in early days and so we’ve only had a few products to look at, but I think the trend suggests favorable timelines.”
Here, BioSpace highlights five mRNA vaccine candidates that could reach patients in the near future.
Pfizer/BioNTech’s PF-07252220
Influenza and an influenza/COVID-19 combo
Since successfully developing COVID-19 vaccine Comirnaty, Pfizer and BioNTech have extended their collaboration to build a pipeline of mRNA vaccines. The next likely candidate for approval is an influenza vaccine, PF-07252220, with Pfizer last year releasing Phase III trial results that demonstrated “superiority to a licensed flu vaccine” in participants 18 to 64 years of age.
The partners also plan to move forward with a combination mRNA vaccine against both influenza and COVID-19. However, this move was struck a recent blow when the companies announced that the vaccine met only one of its two primary immunogenicity endpoints. While specific data were not provided, they reported that the combination vaccine had strong efficacy against influenza A but was weaker against the influenza B strain. The companies said they will consider “adjustments” to the candidate, but this is likely to result in delays before any potential approval and the possibility of losing ground to rivals.
Moderna’s mRNA-1083
Influenza/COVID-19 combo
With Pfizer hitting a stumbling block, Moderna’s COVID-19/influenza vaccine, mRNA-1083, could be the first such combination vaccine to reach the market. In June, the company posted results from a Phase III trial that showed mRNA-1083 produced a strong immune response against both COVID-19 and influenza. In releasing the results, Moderna also became the first and, due to Pfizer/BioNTech’s struggles, only company to date to post positive Phase III results for a combination COVID-19/influenza vaccine.
The efforts by both Pfizer/BioNTech and Moderna can be seen as a strategy to extend the sales enjoyed by the standalone COVID-19 vaccines. One of the obvious marketing benefits would be the ability to provide the vaccine annually, each flu season. An additional selling point could be improved efficacy over existing vaccines, with Moderna stating that its combination vaccine candidate was more effective at providing immunity in adults over the age of 50 than competing influenza and COVID-19 shots.
Moving forward, Moderna plans to add its newly approved RSV vaccine to the combination, creating a triple shot against all three infectious diseases.
GSK/CureVac’s GSK4382276 and GSK4388067
Influenza and, separately, COVID-19
GSK is also targeting both influenza and COVID-19, though currently with separate products. In July, the British multinational bought the global rights to develop CureVac’s investigational mRNA vaccines against COVID-19 (GSK4388067) and influenza (GSK4382276), with the option to develop a combination and an additional vaccine against avian flu. GSK4388067 and GSK4382276 are both currently in Phase II trials and are therefore not too far behind their rivals. On securing full rights to the vaccines, GSK Chief Scientific Officer Tony Wood said in a statement that the company would apply its capabilities “to deliver these promising vaccines at pace.”
Moderna’s mRNA-4157
Head and neck cancer and melanoma
Oncology is one of biopharma’s key markets, and if mRNA vaccines can prove effective in the space, it could be a validation of the technology’s broader therapeutic and commercial potential. Moderna is developing mRNA-4157, a therapeutic vaccine currently being explored in Phase III. The vaccine is being developed in partnership with Merck and paired with Merck’s Keytruda in hopes that it will be able to boost the efficacy of the PD-1 inhibitor to provide a greater anti-tumor effect. The product is currently being trialed in various oncology indications, including head and neck cancer and melanoma.
Heller said that though McKinsey is seeing significant investment go into the therapeutic vaccine space, particularly for those targeting oncology, the “business case needs to be proven.” She added that should mRNA vaccines prove to be effective in the space McKinsey expects a number of follow-on assets to emerge, which could target other indications such as rare diseases. For the moment, the main focus of the vaccine pipeline remains infectious disease and respiratory conditions, Heller said.
Moderna’s mRNA-1647
Cytomegalovirus
Finally, Moderna is developing mRNA-1647 for cytomegalovirus (CMV), the most common infectious cause of birth defects in the U.S. The vaccine is currently being evaluated in Phase III for primary CMV infection in women 16 to 40 years of age.
The first interim analysis of the vaccine’s efficacy is expected by the end of 2024, Moderna stated in March. The company has also advanced indication expansion studies in adolescents 9 to 15 years old and in adult transplant patients. In Phase II results, antigen-specific immune responses were observed at all dose levels in both CMV-seronegative and -seropositive participants, with the vaccine also being found to be generally safe and well-tolerated.
There are currently no approved vaccines to prevent congenital CMV and no treatments for CMV in pregnancy. The virus is typically harmless to adults but can cause a range of health problems in babies and people with a weakened immune system.
https://www.biospace.com/drug-development/5-late-stage-mrna-vaccines-to-watch
FDA Action Alert: BMS, Merck, Sanofi/Regeneron and More
The FDA has six target action dates ahead to round out September as drugs for gastroparesis, Niemann-Pick disease type C and more await decisions.
The FDA has several big decision deadlines coming up, including two for blockbuster drugs seeking to push into new indications and one that could potentially open a new mechanism of treatment for schizophrenia.
Read below for more.
Vanda Proposes Tradipitant to Boost Stomach Emptying
By September 18, the FDA is expected to release its verdict on Vanda Pharmaceuticals’ new drug application (NDA) for tradipitant, an investigational NK-1R antagonist the Pennsylvania-based company is proposing for gastroparesis.
Afflicting around 6 million people in the U.S., gastroparesis is a serious condition that involves the delayed emptying of the stomach. As a result, patients with gastroparesis suffer from nausea, bloating, fullness after meals, vomiting and abdominal pain. Gastroparesis can also compromise social and occupational functioning. Many cases are undiagnosed.
Vanda’s answer to gastroparesis is tradipitant, a small molecule blocker of neurokinin (NK)-1 receptors, which are found in the gastrointestinal tract and in brain regions involved in the vomit reflex. NK-1 receptor antagonists are widely known as anti-emetics, giving tradipitant its potential to suppress the typical nausea and vomiting symptoms that come with gastroparesis.
Vanda’s data package for tradipitant includes clinical efficacy studies, data from a 12-week open-label study, evidence from an expanded-access program and non-animal preclinical toxicology data. The FDA previously placed tradipitant under a partial clinical hold, requiring Vanda to provide a standard, nine-month, non-rodent toxicity study before it could treat patients beyond 12 weeks.
Aside from gastroparesis, Vanda is also developing tradipitant for motion sickness and atopic dermatitis.
Zevra Awaits Verdict on Neimann-Pick Disease Type C Candidate
After clearing the FDA’s newly formed Genetic Metabolic Diseases Advisory Committee last month, Zevra Therapeutics is gearing up for the potential approval of its oral drug candidate arimoclomol for Niemann-Pick disease type C (NPC). The FDA’s deadline is September 21.
NPC is an ultrarare neurodegenerative lysosomal storage disease characterized by the progressive worsening of physical and cognitive function. The condition arises when mutations in the NPC1 and NPC2 genes impair the otherwise normal transport and clearance of cholesterol and other lipids from inside cells, resulting in the toxic buildup of these molecules in various organs, including the brain.
Patients with NPC often suffer from problems with speech, swallowing and movement. The disease is irreversible and can lead to death within months. There are currently no approved therapies for NPC.
Arimoclomol addresses NPC by crossing the blood-brain barrier to make nerves more resistant to destruction, even when under stress.
A panel of outside experts threw its support behind Zevra, voting 11–5 to recommend arimoclomol’s approval, though pointing out that the drug’s overall benefits seemed small.
Heron Awaits FDA’s Go-Ahead for Extended-Release Needle for Zynrelef
Heron Therapeutics is proposing a new extended-release solution vial access needle (VAN) for its local anesthetic Zynrelef (bupivacaine and meloxicam). The FDA is expected to release its verdict on or before September 23.
VAN is designed to “simplify” the preparation of Zynrelef, according to Heron’s news announcement. The new needle will also lower the withdrawal time for the drug to 20 to 45 seconds, down from the previous duration of up to three minutes. Heron calls VAN a “user-friendly” innovation that could also make Zynrelef safer to administer and increase its uptake.
If approved, VAN will replace the vented vial spikes currently deployed for Zynrelef and will be ready for roll-out in the fourth quarter of 2024, according to the biotech’s press release.
Zynrelef is a dual-acting local anesthetic that combines the nerve-blocking effects of bupivacaine and the anti-inflammatory activity of the nonsteroidal drug meloxicam. According to its label, Zynrelef was first approved in 2021 and is indicated for post-surgical pain relief after total knee arthroplasty, open inguinal herniorrhaphy and bunionectomy.
In Phase III studies, Zynrelef demonstrated significant pain reduction within the first 72 hours after surgery while also increasing the percentage of patients who did not require opioids. Zynrelef comes with a boxed warning for serious cardiovascular and gastrointestinal events, which could become fatal.
Merck Tries for Another Keytruda Indication: Pleural Mesothelioma
Merck is seeking to add pleural mesothelioma to the ever-growing label of its blockbuster PD-1 inhibitor Keytruda (pembrolizumab). The FDA’s decision is due September 25.
Pleural mesothelioma refers to malignancies originating in the membrane that lines the walls of the chest and the lungs. It is a rare malignancy most popularly linked with high exposures to asbestos, and case counts in the U.S. have dropped since the substance was banned in 2000, according to the Cleveland Clinic. Around 3,000 patients are diagnosed with mesothelioma each year, with 80% of cases occurring in the pleura.
Merck’s supplemental Biologics License Application (sBLA)—which the FDA accepted and granted Priority Review in May 2024—is backed by data from the pivotal Phase II/III KEYNOTE-483 study.
Results showed that Keytruda plus chemotherapy significantly improved overall survival (OS) in patients with unresectable advanced or metastatic malignant pleural mesothelioma, cutting the risk of death by 21% compared with chemotherapy alone. Progression-free survival was also significantly better in the Keytruda plus chemotherapy arm.
BMS Awaits Landmark Decision for Schizophrenia Drug KarXT
Arguably the FDA’s biggest decision this month is for Bristol Myers Squibb’s KarXT, an investigational muscarinic antipsychotic being proposed for the treatment of schizophrenia. The regulator’s decision is due September 26.
Unlike current treatments for schizophrenia, KarXT works via the dual activation of the M1 and M4 muscarinic receptors and does not directly block dopamine receptors. This unique mechanism of action allows KarXT to ease positive and negative cognitive symptoms in schizophrenia. If approved, KarXT would open up the first new pharmacological treatment approach to schizophrenia in many decades.
KarXT was originally developed by Karuna Therapeutics, which BMS acquired in December 2023 for $14 billion.
The FDA is currently reviewing BMS’ data package for KarXT, which includes findings from the EMERGENT clinical development program. EMERGENT-1 and EMERGENT-2, findings from which were released in 2021 and 2022, respectively, established the efficacy of KarXT in treating schizophrenia on the Positive and Negative Syndrome Scale (PANSS).
EMERGENT-3 then showed in March 2023 that KarXT could significantly improve overall symptom severity. However, this trial missed a key secondary endpoint and revealed potential cardiovascular risks, spooking investors.
In April 2024, BMS unveiled interim findings from the long-term, open-label EMERGENT-4 study, which validated KarXT’s efficacy in schizophrenia, showing that it elicited at least a 30% symptomatic improvement at 52 weeks in more than 75% of treated patients.
Sanofi, Regeneron Tee Up COPD Expansion for Dupixent
Following a delay in May 2024, the FDA is now nearing its deadline to decide on Sanofi and Regeneron’s bid to expand the label of their blockbuster treatment Dupixent (dupilumab) into chronic obstructive pulmonary disease (COPD). The regulator’s verdict is due September 27.
Dupixent is a fully human monoclonal antibody that targets and blocks the IL-4 and IL-13 pathways, in turn moderating the type 2 inflammatory response. This mechanism of action has won Dupixent several approvals in the space, including for atopic dermatitis, asthma and chronic rhinosinusitis with nasal polyps. Dupixent is not immunosuppressive.
The pharma partners are backing Dupixent’s COPD bid with data from the Phase III BOREAS and NOTUS trials. In BOREAS, adding Dupixent to standard of care cut the rate of moderate or severe exacerbations by 30% over 52 weeks, while also boosting lung function and health-related quality of life. Meanwhile, recent data from NOTUS put Dupixent’s efficacy against moderate or severe exacerbations at 34%.
In May 2024, the FDA requested additional efficacy analyses from BOREAS and NOTUS. It noted, however, that the follow-up information would constitute a major amendment to Dupixent’s sBLA, thereby requiring a three-month extension to the review period. Sanofi and Regeneron at the time emphasized that the regulator raised no issues about the approvability of Dupixent in COPD.
https://www.biospace.com/fda/fda-action-alert-bms-merck-sanofi-regeneron-and-more
NuCana Encouraging Data on NUC-7738 Combination in Melanoma
Combination of NUC-7738 plus Pembrolizumab Resulted in Prolonged Progression Free Survival, a Compelling Disease Control Rate including Partial Responses, and a Favorable Safety Profile
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