Merck & Co., Inc. is a global pharmaceutical company based in New Jersey, USA. It was once part of the German Merck Group, founded in 1668. Known as Merck Sharp and Dohme or MSD in other parts of the world, the company is one of the world’s biggest manufacturers. It is among the world’s leading pharmaceutical companies, ranking usually in the first five drug makers globally in terms of sales.

Merck was established in 1891 as the American subsidiary company of the Merck Group. Merck grows and synthesizes drugs, vaccines, and biological and molecular treatments, also over animal healthcare. It has several best-selling drugs, such as cancer immunotherapy, anti-diabetic drugs, and vaccines for HPV and chickenpox, which collectively hold a high market value as of the period ending 2020.

The company said the drug achieved the primary endpoint of cutting the time to disease progression, lung transplantation, or death by half in a phase III trial involving 172 patients with the advanced stages of the illness on standard background therapy.
The disorder is present in approximately 40,000 patient populations across the country. An independent data monitoring committee has advised early termination of the study but would allow participants to continue to receive the treatment, Merck said.

Winrevair presently costs about $238,000 per year and was the first treatment from the class of drugs that targets a type of protein called activin. The drug accounts for $149 million in sales in the third quarter in Merck despite controversy over potential bleeding risk. “That’s why Winrevair seems safe to us despite potential side effects in severe patients — to which, most likely, it will restrict itself,” the Oppenheimer analysts said in a note earlier this month.

This combination is hoped to provide insight into whether there is a correlation between these factors and migraines.

People can be encouraged to complete the surveys through the proximal rewards in the form of points and in turn, more information, such as pharmacy claims and electronic health records can be acquired for further understanding of normal migraine treatments.

An initial pilot study of the MigraineSmart program, involving 3,492 participants, revealed the following findings:

– In terms of treatment, participants were asked what medications they took for their symptoms and 43% of them reported to have used prescription drugs. Triptans topped the list of medications used.
– From the migraines days to the other days, the participants were found to be moving an average of 50% less per day.
– More than half of the participants admitted that they have shared or would share their monthly MigraineSmart report with their physicians.

MigraineSmart is a multi-component platform that includes survey information as well as ePRO, wearables, and evidence-based content in the Evidation app.

In another survey of a considerably higher population of 21,707 people, more than 40% reported having not sought professional healthcare for the ailment in the previous year.

The pilot research also supported the hypothesis and the participants provided data that they are less physically active and took only half of the usual steps when they had a migraine. Migraines can be a chronic condition, and it is estimated that over 40 million people in the United States have been diagnosed with it.

Migraine is a recurrent and painful type of headache, which more than 40 million Americans experience- women are more vulnerable to this condition as compared to men. These headaches can, therefore, cause a good deal of discomfort, affecting physical and mental health, work productivity, and social interactions. As far as the factors concerning migraines, they are believed to be caused by genetic, environmental, and other factors.

Neuren CEO Jon Pilcher expressed great excitement about the results of their first clinical trial with Pitt Hopkins patients. He underlined the underprivileged community’s pressing unmet needs and the fact that they could now move closer to creating the first licensed treatment. Pilcher also expressed his sincere gratitude to the Pitt Hopkins community and the American trial sites for their contributions to the successful conclusion of this challenging, innovative trial.

16 kids between the ages of 3 and 17 (average age of 9) from five US hospitals participated in the open-label Phase 2 trial. The safety, acceptability, pharmacokinetics, and effectiveness of NNZ-2591 were evaluated during this 13-week trial. The study involved administering NNZ-2591 as an oral liquid dose two times daily to the participants. The dose was increased gradually over the first 6 weeks to achieve the target dose of 12 mg/kg, subject to an independent safety and tolerability review.

Before beginning the 13-week treatment period, the trial involved at least 4 weeks of screening and observation to determine baseline characteristics. A follow-up assessment was conducted 2 weeks after the treatment period ended to wrap up the trial.

This initial trial’s primary objectives in regard to children with PTHS were to assess pharmacokinetics, safety, and tolerability. Secondary objectives comprised ten additional efficacious measures that have been used in other neurodevelopmental disorders but were not specifically designed for PTHS, as well as four measures that were specifically tailored for PTHS and evaluated by both clinicians and caregivers.

NNZ-2591 showed a favorable safety record. Most Treatment Emergent Adverse Events (TEAEs) were not judged to be related to the study medication, and all of them were mild to moderate in nature. No Serious TEAEs occurred, and no significant patterns emerged in laboratory values, ECGs, or other safety parameters recorded during the treatment period.

11 subjects finished the trial. One participant withdrew from the study because they were unable to fulfill the safety monitoring requirements outlined in the protocol. TEAEs caused the discontinuation of four subjects, all of which were resolved. For two of these subjects, the TEAEs (COVID-19 and minor vomiting/diarrhea/lethargy) were considered unrelated to the study drug. For the other two subjects, the TEAEs (slight constipation/abdominal discomfort/fatigue and mild sleep issues) were shown to be related to the study drug.

The average improvement from baseline showed statistical significance (Wilcoxon signed rank test p<0.05) across all four efficacy measures tailored for Pitt Hopkins syndrome, both when considering only the subjects who completed the study (n = 11) and when including those who discontinued (n = 15). Conversely, changes from baseline did not exhibit statistical significance for the efficacy measures not originally intended for PTHS but utilized in other neurodevelopmental conditions.

Unless the aforementioned issues are fixed the agency has refused to approve the drug under the accelerated review pathway. When a submission was initially made to the agency it was supplemented by the phase 1 ELM-1 study and the phase 2 ELM-2 study.

In order to support the approval for the bispecific antibody in R/R diffuse large B-cell lymphoma and relapsed/refractory (R/R) follicular lymphoma the company is currently running 5 trials.

Andres Sirulnik who serves as the senior vice president, of translational and clinical sciences for hematology has downplayed these concerns by claiming that enrollment is coming along just fine and that the company is on teh cusp of satisfying the demands made by the FDA.

While randomization in trials hasn’t begun yet by the time Regeneron files for accelerated approval these matters will be dealt with.

Sirulnik was quick to clarify though that no concerns were raised by the regulatory agency when it came to the safety or efficacy of the drug, the only point of contention has been on the technical aspect of the trials.

Since the company wanted to move the treatment up in line the agency wanted a safety lead-in test to be conducted prior to the randomization process. Before proceeding any further, safety was a big priority for the FDA, therefore for each of the studies and indications mentioned, they wanted to see a small group of patients, Sirulnik explained. According to him, the only thing holding them back is that all the patients are in the safety lead-in in all these studies, as soon as the safety lead-in is clear, the company can begin the randomization phase.

The FDA’s emphasis on confirmatory trials is a new thing, in the past when based on a surrogate endpoint for conditions with an unmet need, certain drugs were approved on accelerated grounds. It was later these copies who had to conduct confirmatory trials to gain full approval.

Now though, the agency has tightened the nose around everyone’s neck and all companies are expected to have the studies “well underway” at the time of filing. This, however, has proved to be an issue since the definition of well underway has not been clarified by the agency.

While Regeneron has not announced when it will be submitting its application for the approval of odronextamab, representatives of the company are still hopeful that once back in the hands of the agency it will be reviewed under the accelerated pathway.

Alcon’s AR-15512 Breakthrough for Dry Eye Disease

Alcon’s $770 million acquisition of Aerie Pharmaceuticals proves strategic as AR-15512, the lead candidate, demonstrates promising results in two phase 3 trials for dry eye disease. The trials show a significant increase in tear production after a 14-day regimen, meeting the primary endpoint. Alcon, aiming for FDA approval by mid-2024, highlights early observations of tangible improvements in tear production from the first day of treatment, positioning AR-15512 as a potential groundbreaking treatment for the prevalent condition affecting an estimated 38 million Americans.

Harvard-Engineered Virus-Like Particles for Vision Restoration

Researchers from Harvard and the Broad Institute, led by Dr. David Liu, make strides in vision restoration in blind mice using prime editors delivered through novel particle systems. The study showcases the successful use of prime editor-engineered virus-like particles (PE-eVLPs) for therapeutic prime editing in animals, enhancing efficiency and addressing safety concerns. The results demonstrate the potential of optimized PE-eVLPs for in vivo correction of genetic mutations, marking a significant advancement in prime editing technology and its application in therapeutic interventions.

GSK’s $1 Billion Acquisition of Aiolos Bio for Asthma Medicine

GSK is acquiring Aiolos Bio and its phase 2 asthma medicine, AIO-001, for an initial payment of $1 billion and up to $400 million in regulatory targets. AIO-001, considered a potential best-in-class treatment, targets a unique population of asthma patients with low T2 inflammation. GSK aims to expand research into other indications and conduct a phase 2 study in people with asthma, positioning AIO-001 as a promising addition to GSK’s biologics portfolio.

Curevo Vaccine’s Success in Shingles Vaccine Market

Curevo Vaccine’s CRV-101, a non-mRNA adjuvanted subunit vaccine, proves successful in a phase 2 trial against GSK’s Shingles vaccine. CRV-101 demonstrates a strong immune response, surpassing Shingrix, with lower rates of adverse events. Curevo strategically emphasizes the vaccine’s safety profile as a potential market differentiator, foreseeing greater acceptance of shingles vaccination if confirmed in a phase 3 trial.

Novo Nordisk’s Research Agreements with Omega Therapeutics and Cellarity

Novo Nordisk enters substantial research agreements with Omega Therapeutics and Cellarity, both incubated by Flagship Pioneering, as part of a broader collaboration targeting cardiometabolic and rare diseases. Novo Nordisk will provide funding for research and development, potentially reaching $532 million, and tiered royalties. Omega Therapeutics focuses on programmable epigenomic mRNA medicines for obesity, while Cellarity aims to develop a small molecule therapy for metabolic dysfunction-associated steatohepatitis (MASH), addressing significant unmet patient needs in these areas.

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 This rare and often fatal disease impacts a global population of 40,000 individuals, as highlighted in a joint press release disseminated by the pharmaceutical collaborators.

The FDA’s nod was underpinned by robust phase 3 data showcasing Wainua’s consistent and sustained efficacy across various outcome metrics. These encompassed significant improvements in serum transthyretin concentration, reductions in neuropathy impairment, and noteworthy enhancements in the overall quality of life for the patients.

What sets Wainua apart is its user-friendly auto-injector format, empowering patients to administer the treatment every month independently. This feature confers a distinct advantage over Alnylam’s Onpattro, necessitating subcutaneous delivery at specialized treatment centers.

Despite the existence of alternatives such as Onpattro, the unmet needs for this genetic disease persist at alarming levels. According to Brett Monia, Ph.D., Ionis’ CEO, over 80% of patients with the disease remain untreated, owing to a combination of insufficient disease awareness and a prevalence of misdiagnoses.

AstraZeneca entered into this collaboration in 2021, offering a substantial upfront payment of $200 million to secure exclusive ex-U.S. commercialization rights. Under the agreement, AstraZeneca is responsible for the commercial supply, committing to payments of up to $485 million in development and approval milestones, along with potential sales-related milestones totaling up to $2.9 billion.

The collaborative synergy between Ionis’ extensive expertise in amyloidosis and rare diseases and AstraZeneca’s prowess in cardiovascular diseases, coupled with its global reach, positions the two entities to cater to a broader patient demographic. Monia expressed confidence that this collaboration would enable them to reach “as many patients as possible.” Meanwhile, AstraZeneca views the approval as the inception of an “exciting journey” in the amyloidosis field, according to Ruud Dobber, Ph.D., executive vice president and president of AstraZeneca’s biopharmaceuticals business unit.

The journey for Wainua doesn’t culminate with this approval. The next phase involves a meticulously planned label expansion to address transthyretin amyloid cardiomyopathy (ATTR-CM), affecting an estimated 400,000 to 500,000 patients globally. Ionis and AstraZeneca are currently conducting what Monia describes as the “largest study ever conducted” in ATTR-CM, with results expected in 2025.

In the realm of ATTRv-PN, Wainua contends primarily with Alnylam’s Onpattro, which received approval in 2018 as the pioneer medication for this condition. While both Ionis and Alnylam initially harbored aspirations for an ATTR-CM expansion, Alnylam abandoned these hopes after the FDA denied approval earlier this year.

Pfizer’s tafamidis, marketed as Vyndamax and Vyndaqel, secured approval in 2019, making it the trailblazer in the ATTR-CM space. Analysts have underscored that Pfizer’s early market entry may pose challenges for competitors, characterizing the options as “difficult to displace” and appearing “quite entrenched.”

This breakthrough not only significantly enhances the efficiency of manufacturing pseudouridine but also eliminates a troublesome impurity, alpha-pseudouridine, commonly present in chemically synthesized beta-pseudouridine. EnginZyme’s enzymatic approach has the potential to revolutionize the production of vaccine ingredients, making it cleaner, more efficient, and environmentally friendly.

EnginZyme, in partnership with CDMO (Contract Development and Manufacturing Organization) Ajinomoto Bio-Pharma Services, aims to support global efforts to strengthen the vaccine supply chain by offering pseudouridine at reduced prices to interested buyers. Notably, the companies have already produced a substantial quantity of pseudouridine, sufficient for more than 500 million vaccine doses, in a facility compliant with cGMP regulations.

The enzymatic method developed by EnginZyme represents a significant leap forward in comparison to traditional chemical synthesis techniques. 

Their research, conducted over 15 years before the COVID-19 pandemic, demonstrated that substituting pseudouridine for uridine in messenger RNA could eliminate inflammatory side effects, ultimately propelling mRNA-based vaccines into the spotlight.

The COVID-19 crisis exposed a critical need for vaccine doses in low- and middle-income countries, hindered by production limitations, wealthier nations’ hoarding, and price-focused distribution. EnginZyme’s CEO, Karim Engelmark Cassimjee, noted that their cost-efficient pseudouridine production process could contribute to the resilience of the global healthcare supply chain, offering academic and nonprofit organizations the opportunity to access free samples for research purposes.

Geert Schelkens, the R&D Manager at Ajinomoto Bio-Pharma Services, emphasized the project’s sustainability aspect. The biocatalytic process brings about a notable decrease in the project’s environmental impact, aligning perfectly with their sustainability objectives. Through their collaboration with EnginZyme, Ajinomoto Bio-Pharma Services anticipates substantial enhancements in the worldwide supply chain for vaccine ingredients.

Derived from pseudouridine, N1-methylpseudouridine-5’-triphosphate plays a pivotal role in stabilizing and reducing the immunogenicity of mRNA, a technology that achieved considerable recognition through the success of COVID-19 vaccines from Pfizer-BioNTech and Moderna. 

Matthew Thompson, Head of Enzyme Development and Innovation at EnginZyme, emphasized the efficiency and sustainability of enzymatic pseudouridine synthesis, which aligns with their broader vision of minimizing waste, energy consumption, and environmental impact in chemical manufacturing.

EnginZyme states that its overarching mission revolves around redefining the field of chemistry by harnessing the potential of enzymes to facilitate sustainable and cost-effective production across various industries. Their patented enzyme immobilization technology allows for biomanufacturing without the reliance on living organisms, offering a cleaner and more environmentally responsible alternative to traditional chemical processes.

Nkarta publicly disclosed that the FDA had granted the company permission to initiate human trials for NKX019 in lupus nephritis. This announcement catalyzed a substantial increase in Nkarta’s stock price, which soared from $1.47 per share at the market’s opening to $3.14 by the close of the trading day. Their allogeneic CAR NK cell therapy candidate, which specifically targets CD19, is currently in the midst of a phase 1 clinical trial for patients afflicted by B-cell malignancies. The release of top-line data from this trial is eagerly anticipated in the coming year.

With this announcement, Nkarta has embarked on a corporate restructuring initiative that includes a reduction in its workforce. According to documents filed with the Securities and Exchange Commission (SEC) on October 16, the company is poised to terminate the employment of 18 individuals.

This groundbreaking shift towards applying cell therapy in conditions other than cancer is underpinned by a noteworthy German study featuring five patients diagnosed with systemic lupus erythematosus (SLE) who underwent CAR-T cell therapy. Published in Nature Medicine last year, this study unveiled the remarkable finding that all five patients achieved remission within a three-month timeframe, a remission that persisted even after the re-emergence of B cells more than three months later.

Nkarta’s forthcoming trial will take the form of a multicenter, open-label, dose-escalation study involving patients grappling with refractory lupus nephritis. In this trial, patients will receive three doses of NKX019 administered on three separate occasions, with one week separating each dose. The treatment regimen commences after lymphodepletion with cyclophosphamide, an immunosuppressive drug well-known for its safety record in lupus and its application in chemotherapy. The trial is anticipated to encompass a maximum of 12 patients, and the initiation of the first patient’s participation is scheduled for the first half of 2024.

To accelerate the advancement of NKX019, Nkarta has established a strategic partnership with Lupus Therapeutics, which serves as a clinical research affiliate of the Lupus Research Alliance.

Presently, the armamentarium for lupus treatment encompasses GSK’s SLE drug Benlysta, a biologic therapy that secured FDA approval in 2011 and recorded over $1 billion in revenue last year. Another treatment option is AstraZeneca’s Saphnelo, an intravenous infusion that received approval for SLE patients in 2021.

Beta Bionics Secures $100 Million for Artificial Pancreas Expansion 

Beta Bionics, a company in the field of medical technology, has managed to secure an impressive $100 million in funding. This financial boost comes hot on the heels of receiving crucial FDA approval for their groundbreaking artificial pancreas system, iLet. This innovative device aims to revolutionize the lives of those dealing with diabetes by automating the delicate balancing act of insulin and glucagon delivery. With this substantial funding injection, Beta Bionics can now embark on an ambitious expansion plan, bringing them one step closer to their mission of significantly improving the daily lives of individuals grappling with diabetes.

Asensus and NVIDIA Collaborate on Digital Surgical AI

Asensus Surgical, a leader in surgical technology, and NVIDIA, a powerhouse in high-performance computing, have joined forces in a landmark collaboration set to transform the world of surgery. By marrying Asensus Surgical’s cutting-edge surgical robotics platform with NVIDIA’s exceptional computing capabilities, the duo is committed to creating next-generation AI-driven solutions for the field of surgery. This partnership represents a pivotal stride forward in the realm of digital surgery, promising to enhance precision and patient outcomes through the integration of artificial intelligence.

TrialBee’s New Tool Aims to Expedite Clinical Trial Recruitment Delays

TrialBee, a player in the realm of clinical trial recruitment technology, has unveiled a tool aimed at tackling the persistent issue of delays in clinical trial recruitment. Leveraging the power of artificial intelligence and data analytics, this innovative tool streamlines the process of matching eligible patients with suitable clinical trials. By doing so, it holds the potential to significantly accelerate the development of new medical treatments and therapies, ultimately benefiting both patients and the medical research community.

European Commission Approves Updated Pfizer-BioNTech Vaccine for Omicron Variant

The European Commission has granted approval for an updated version of the Pfizer-BioNTech COVID-19 vaccine, specifically tailored to combat the Omicron XBB-1.5 variant. This development underscores the remarkable agility of vaccine manufacturers in responding to emerging viral variants. By adapting their vaccine formulations to address evolving strains of the virus, they ensure that individuals continue to have access to effective protection against the ever-changing landscape of COVID-19.

Marketing Authorization Granted for AbbVie’s Migraine Therapy, Aquipta

AbbVie, a prominent pharmaceutical company, has achieved a significant milestone by receiving marketing authorization from the Medicines and Healthcare Products Regulatory Agency (MHRA) for its migraine therapy, Aquipta. For individuals who have long endured the debilitating effects of migraines, this authorization brings a glimmer of hope. Aquipta represents a potential breakthrough in migraine management, offering a new avenue for relieving the symptoms and improving the overall quality of life for those afflicted by this condition. The marketing authorization now paves the way for wider accessibility to this promising treatment, bringing much-needed relief to migraine sufferers.

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