Clinical – Life Sciences Voice

Moderna Delays Flu-COVID Combo Vaccine Filing Amid FDA Request

Editorial Team — Thu, 22 May 2025 21:29:08 +0000

Moderna has announced that it is withdrawing its application for approval from the U.S. Food and Drug Administration (FDA) for its combination flu and COVID-19 vaccine, identified as mRNA-1083.
According to the company, it intends to submit the application again later in the year. The decision to resubmit will be timed to follow the availability of efficacy data from a phase 3 clinical trial of Moderna’s standalone flu vaccine, mRNA-1010.
The original application for mRNA-1083 had been filed last year. Based on that submission, the company had been on track to potentially secure FDA approval for the vaccine for adults aged 50 and above by November 2025. However, at the beginning of May, Moderna revised its expectations, shifting the anticipated timeline for approval to 2026. This adjustment followed a request from the FDA, in which the agency asked to review phase 3 efficacy data prior to making any decision on whether to authorize the vaccine.
The company has stated that the decision to withdraw the application was made voluntarily. Moderna now plans to refile the application once interim data from its ongoing phase 3 trial of mRNA-1010 are available. The trial is currently in progress, and the company expects to have preliminary results this summer.

Stephen Hoge, M.D., who serves as the president of Moderna, addressed the FDA’s request and the company’s response during an earnings call held at the beginning of May. He noted that Moderna is approaching the point at which data will become available from a 40,000-participant study evaluating the mRNA-1010 flu vaccine. In that context, Hoge remarked, “It makes good scientific sense that that would be a part of the review that’s going on for our flu-COVID combination.”
At the time of the call, Moderna had not yet decided whether it would include the data in an amendment to the existing biologics license application (BLA) or submit a new application altogether. “It is totally appropriate to submit that data as an amendment to the BLA,” Hoge said. “It could also be, from a pragmatic perspective, it makes sense to update more broadly the BLA submission with it, which could result in a resubmission.” He added that Moderna would proceed with whichever option appears most practical and aligns with the direction provided by the FDA.

Hoge further explained that Moderna’s interactions with the FDA have remained consistent. Describing the situation, he said it had been “business as usual” with regard to communications, and he stated that the company continues to maintain “productive exchanges” with the agency concerning all of its current file reviews.
Although the company has not specified an exact date for when it intends to resubmit the application, it has confirmed that the filing will follow the release of the phase 3 efficacy data from mRNA-1010 later this year.

Boehringer’s Nerandomilast Advances in IPF Amid Analyst Reservations

Editorial Team — Thu, 22 May 2025 20:06:32 +0000

Boehringer Ingelheim’s presentation of phase 3 data for its idiopathic pulmonary fibrosis (IPF) drug candidate nerandomilast has received a reserved response from analysts, who described the treatment as “a step forward but not game-changing.”
The company had previously disclosed in September that the study met its primary endpoint, raising expectations for a potential improvement over existing antifibrotic therapies, namely Boehringer’s Ofev and Roche’s Esbriet.

The study enrolled 915 patients, 78% of whom were receiving background antifibrotic treatment—535 on Ofev and 380 on Esbriet. Results showed that at Week 52, patients receiving a high dose of nerandomilast had a mean lung capacity decline of −114.7 ml, compared to −183.5 ml in the placebo group. Among those using Ofev, the decline was −118.5 ml with nerandomilast versus −191.6 ml on placebo. The smallest difference was observed in the subgroup of patients taking Esbriet, where the low dose of nerandomilast performed worse than placebo.
In a note dated May 19, Leerink Partners analysts commented that nerandomilast “looks to us to be an incrementally better Ofev,” but emphasized it remains a disease-slowing rather than disease-halting agent. They characterized it as “a decent Ofev-successor” but noted that its “modest effect size” was unlikely to prompt immediate changes in IPF treatment practices.
Concerns were also raised about the drug’s interactions with current therapies. According to Boehringer, drug-drug interactions between nerandomilast and Esbriet were responsible for the low dose’s failure to improve outcomes in that subgroup. In addition, overlapping toxicity was observed with Ofev. Diarrhea was the most frequently reported adverse event, affecting 41% of patients on the high dose of nerandomilast and occurring most often among those concurrently using Ofev.

Leerink analysts pointed out that this overlap in tolerability could limit the feasibility of using nerandomilast alongside Ofev. “Diarrhea leading to discontinuation was mainly observed with background [Ofev] use, which we think may limit the number of patients who are able to tolerate concurrent use,” they wrote.
While the analysts acknowledged that nerandomilast demonstrated a “solid profile that warrants approval,” they also highlighted the opportunity this leaves for other developers in the IPF space. The perceived limitations of nerandomilast were cited as a positive development for PureTech Health and MannKind, both of which are currently advancing their own IPF programs.

Vertex Presses Pause on CF Study, Reports Major Write-Down

Editorial Team — Fri, 09 May 2025 04:23:34 +0000

Vertex Pharmaceuticals has announced a temporary pause in part of a clinical trial evaluating its cystic fibrosis (CF) candidate, VX-522, due to a tolerability concern. The update was included in the company’s release and comes alongside a separate $379 million impairment charge tied to a discontinued diabetes program.
The trial pause affects the multiple ascending dose segment of the phase 1/2 study of VX-522, an experimental mRNA therapy developed in partnership with Moderna. Vertex did not disclose specific details regarding the tolerability issue but stated more information would be provided as it becomes available. The company emphasized the temporary nature of the pause.

VX-522 is a nebulized mRNA-lipid nanoparticle (LNP) therapy designed to address the root cause of CF by enabling lung cells to produce functional CF transmembrane conductance regulator proteins. The candidate received fast-track designation from the U.S. Food and Drug Administration. The collaboration between Vertex and Moderna began in 2020, with Vertex providing $75 million to support a three-year research effort that resulted in the development of VX-522.
Analysts from William Blair described the trial pause as “unfortunate” but noted that the decision to temporarily halt, rather than terminate, the study suggests Vertex remains encouraged by data collected so far. The trial is being conducted as an open-label study, which may provide continued insights despite the pause.
The CF program update comes as competitors in the inhaled mRNA-LNP space, including Arcturus Therapeutics and ReCode Therapeutics, are expected to share clinical data in the near term. The competitive landscape could shift depending on how these therapies progress through development.
In addition to the trial pause, Vertex reported a $379 million intangible asset impairment charge. The charge is linked to the discontinuation of VX-264, an islet cell therapy for diabetes that was combined with a delivery device. The decision to cease work on VX-264 followed results from a phase 1/2 trial that indicated the treatment was unlikely to produce adequate insulin levels. The write-down impacted the company’s GAAP operating income for the first quarter of the year.

This is the latest in a series of pipeline adjustments by Vertex, which recently concluded its work with adeno-associated virus (AAV) vectors used in gene therapy delivery. The shift was disclosed at the end of the prior week.
Despite the changes, William Blair analysts have maintained an “outperform” rating on Vertex’s stock, citing what they described as ongoing clinical progress and disciplined business development. Vertex continues to advance a diversified pipeline, including zimislecel, a beta-cell therapy for Type 1 diabetes that requires immunosuppression and may be submitted for regulatory review in the coming year.

J&J Gene Therapy Treatment For Vision Loss Fails to Meet Primary Endpoints

Editorial Team — Wed, 07 May 2025 18:49:13 +0000

Johnson & Johnson acquired the entire rights to a gene treatment for a rare condition some years ago; the pharmaceutical giant may now be going through buyer’s remorse. The therapy did not enhance vision-guided mobility in individuals with X-linked retinitis pigmentosa (XLRP) during a phase 3 study, as reported on May 2.

The LUMEOS trial included 95 participants, 58 of whom were administered either a low or high single injection of botaretigene sparoparvovec (bota-vec), an experimental gene therapy utilizing an adeno-associated virus to deliver a functioning variant of the retinitis pigmentosa GTPase regulator (RPGR) gene to the retina.

XLRP is an unusual and aggressive variant of retinitis pigmentosa, an advanced eye condition that results in the degeneration of photoreceptors, which eventually results in blindness. The illness typically appears in childhood and mostly impacts males, with the LUMEOS study recruiting just a limited number of women affected by the condition.

In the collective evaluation of all participants who received bota-vec, the trial’s main aim of enhancing patients’ capacity to visually go through a virtual maze was not achieved; nonetheless, J&J indicated that the results were directionally favorable.

“We’re working to understand the totality of the data, inclusive of the clinical relevance of improvement shown on the majority of secondary endpoints, as we evaluate strategic options and next steps,” a J&J spokesperson stated.

All patients administered Bota-vec encountered at least a solitary treatment-emergent negative effect, with 86% of them classified as mild or severe, as per the statement. 53% of individuals had at least one negative outcome related to Bota-vec.

Bota-vec was associated with improvements in many secondary endpoints of the experiment, notably patient-reported eyesight and ratings on a letter chart vision assessment. Although the findings exhibited a p-value less than .05, the values are intended only for descriptive reasons and were not presented as statistically significant by the firm.

According to Johnson & Johnson, out of the 55 individuals who were treated, 22 of them exhibited improvement on multiple endpoints, while one patient in the control group did not demonstrate any improvement. As of the 25th of April, the firm continued to conduct a phase 3 follow-up research for patients participating in the original late-stage experiment.

Initially, the Janssen division of Johnson & Johnson worked along with the genetic medicines biotech company MeiraGTx to create Bota-vec technology. In a deal that could potentially be worth $415 million, Johnson & Johnson purchased the complete rights to the program at the end of December 2023.

Pfizer’s PD-1 Inhibitor Shows Mixed Results in Bladder Cancer Trial

Editorial Team — Tue, 29 Apr 2025 17:48:56 +0000

Pfizer has announced detailed results from its Phase 3 trial evaluating sasanlimab, a subcutaneous PD-1 inhibitor, in combination with Bacillus Calmette-Guérin (BCG) as a first-line treatment for high-risk, non-muscle invasive bladder cancer. The data, presented at the 2025 American Urological Association Annual Meeting, revealed a 32% reduction in the risk of disease-related events. However, the study did not meet all its secondary objectives and showed an increased rate of serious adverse events in the sasanlimab treatment arm.
The primary endpoint of event-free survival (EFS), defined by recurrence of high-grade disease, progression, persistence of carcinoma in situ, or death from any cause, favored the sasanlimab plus BCG induction and maintenance regimen. At 36 months, 82.1% of patients receiving the combination were free from events compared to 74.8% in the control cohort.

Despite achieving the primary EFS endpoint, other findings tempered the overall outcome. In a third cohort where patients received sasanlimab and BCG induction but no maintenance doses, event-free survival outcomes were not superior to the standard of care. This result indicated the necessity of maintaining BCG as a part of the regimen if sasanlimab is incorporated into treatment protocols.
Key secondary endpoints revealed further limitations. Specifically, sasanlimab did not improve overall survival (OS) compared to the standard treatment. These results were collected after a median follow-up period of 40.9 months, with final analysis still pending.
The safety profile of sasanlimab in combination with BCG was reported as generally consistent with previous data. Nonetheless, a notable difference was seen in the incidence of serious treatment-related adverse events. The rate was 17.7% in the sasanlimab plus BCG induction and maintenance group, compared to 1.4% in the control group. Hepatitis and pancreatitis emerged as the most common grade 3 or 4 immune-mediated adverse events among patients treated with sasanlimab, although most cases were managed effectively with thyroid hormone supplementation.

Pfizer has submitted the trial results to health authorities to support potential regulatory filings. If approved, sasanlimab could become the first PD-1 inhibitor authorized for first-line treatment of high-risk, non-muscle invasive bladder cancer. Currently, Merck & Co.’s Keytruda holds approval only for patients unresponsive to BCG. Regulatory approval of sasanlimab could also facilitate Pfizer’s broader plans to integrate the drug with its antibody-drug conjugate therapies.

Medtronic Highlights Improved Results with Affera PFA Technology

Editorial Team — Tue, 29 Apr 2025 17:42:34 +0000

Medtronic has announced encouraging clinical outcomes from two studies evaluating its pulsed field ablation (PFA) technologies. These studies focused on the Affera family of solutions, including the latest Sphere-360 single-shot PFA catheter and the Sphere-9, a dual-energy focal PFA and mapping catheter. The findings were presented at the Heart Rhythm Society (HRS) 2025 Annual Meeting in San Diego, alongside additional data regarding Medtronic’s OmniaSecure defibrillation lead.
Affera’s technologies have been integrated into Medtronic’s broader PulseSelect PFA system, the first FDA-cleared platform specifically for treating atrial fibrillation (AFib). This integration allows for comprehensive visualization and electroanatomical mapping during procedures. Medtronic acquired Affera in August 2022 through a $1 billion deal, expanding its leadership in cardiac electrophysiology. In 2024, the company also secured FDA approval to explore the use of this system for ventricular tachycardia (VT) treatment.
Rebecca Seidel, president of Medtronic’s Cardiac Ablation Solutions business, emphasized the company’s dedication to innovation and patient care. “These results represent a significant step forward as we work to advance treatment options and solidify our leadership in electrophysiology,” she stated.

The Sphere-360 catheter, currently under investigation, is designed to simplify AFib procedures through efficient, durable ablations using pulsed field energy. Its unique design features a large, flexible lattice tip that delivers energy across its surface without requiring multiple rotations, a step that distinguishes it from traditional technologies. Additionally, it employs the smallest sheath size (8.5 Fr) among single-shot PFA devices.
A year-long, multi-center trial evaluating Sphere-360 in patients with paroxysmal AFib showed an impressive 88% rate of freedom from arrhythmia recurrence. Moreover, the device achieved durable pulmonary vein isolation (PVI) in 98% of targeted veins. No safety events were recorded among patients treated with the most optimized waveform settings. Medtronic plans to launch a pivotal U.S. trial for Sphere-360 later this year.
Dr. Vivek Reddy, director of cardiac arrhythmia services at Mount Sinai Health System, praised the system’s performance, noting its intuitive integration and potential to streamline procedures without sacrificing precision. He highlighted that Sphere-360’s design allows for efficient circumferential lesions without requiring catheter rotation, with a strong safety and efficacy profile.
The Sphere-9 catheter, another Affera innovation, utilizes a smaller 9 mm nitinol lattice tip to deliver both radiofrequency (RF) and pulsed field energy. In contrast to the Sphere-360, which is intended to address larger areas around the pulmonary veins, the Sphere-9 catheter is built for more precise, focal treatments — an important feature for performing linear ablations that are often paired with PVI when managing persistent AFib.

A detailed sub-analysis from the Sphere Per-AF IDE study showed that the Sphere-9 could safely and successfully create linear lesions, helping to boost the chances of sustaining a normal heart rhythm. Findings from the broader Sphere Per-AF trial ultimately supported the FDA’s approval of the Affera system in October 2024, reinforcing Medtronic’s leadership in the field of cardiac ablation therapy.

VelaVigo Bio Strikes Second Major Licensing Agreement, Transfers Bispecific Rights to Ollin Biosciences

Editorial Team — Wed, 23 Apr 2025 16:57:29 +0000

In a continued series of strategic moves, VelaVigo Bio, a biotechnology firm based in Shanghai, has finalized its second significant transaction within a six-month span. The latest agreement involves the licensing of ex-China rights to VBS-102, a bispecific asset, to U.S.-based Ollin Biosciences. The total potential value of the deal reaches up to $440 million, a figure that includes an initial payment along with contingent payments tied to future developmental, regulatory, and commercial milestones. VelaVigo is also positioned to earn tiered royalties based on eventual sales within Ollin’s geographical domain.

This announcement follows a similar licensing deal executed by VelaVigo in November of the previous year, when the company partnered with Avenzo Therapeutics. That transaction involved a Nectin4xTROP2 bispecific antibody-drug conjugate, for which Avenzo secured ex-China rights. Initial and near-term payments under that agreement could reach $50 million, with the total potential value soaring to $750 million contingent upon successful achievement of specified benchmarks. The company further reinforced its financial standing earlier this year by completing a $50 million funding round in February.
The new licensing arrangement marks another step in VelaVigo’s broader strategy to monetize its pipeline assets by granting territorial rights outside of China, while maintaining domestic control. VBS-102, the focus of the Ollin deal, will now be developed and potentially commercialized by the U.S. biotech, subject to performance and regulatory success.
Ollin Biosciences, a relatively new entrant in the biotech space, has maintained a focus on ophthalmology. In January 2024, the company filed a trademark application for “OLLIN,” citing coverage for pharmaceutical agents intended for treating and preventing ophthalmic diseases and disorders. Ollin is also supporting academic research in this domain, having awarded funding to a professor at Duke University who is conducting a project on the interplay of ocular outflow targets, specifically in the context of glaucoma.
Leadership at Ollin includes Jason Ehrlich, who is identified as the company’s Chief Executive Officer. Ehrlich brings a background in ophthalmic drug development, with past roles including Chief Medical Officer at Kodiak Sciences and earlier tenure as global head of clinical ophthalmology at Genentech. Though Ollin has not publicly detailed its investor base, industry connections suggest a link to Arch Venture Partners. Paul Berns, a managing partner at Arch, serves on Ollin’s board of directors. The company’s foundation also includes Atul Dandekar, who previously held executive responsibilities at Maze Therapeutics, another Arch-supported enterprise.

The financial and strategic implications of VelaVigo’s recent transactions indicate a deliberate effort to engage international collaborators while reinforcing its capital base. The deals with Avenzo and Ollin, in addition to securing non-dilutive funding, enable VelaVigo to leverage regional expertise in development and commercialization without relinquishing its foothold in the domestic Chinese market.

Lilly’s Orforglipron Demonstrates Semaglutide-Like Efficacy in Phase 3 Type 2 Diabetes Trial

Editorial Team — Fri, 18 Apr 2025 20:48:16 +0000

Eli Lilly’s oral GLP-1 receptor agonist orforglipron has met its primary efficacy endpoint in a Phase 3 trial, showing reductions in A1C and body weight on par with injectable semaglutide (Ozempic), Novo Nordisk’s leading single-acting GLP-1 therapy.
In a recent earnings call, Daniel Skovronsky, M.D., Ph.D., Lilly’s Chief Scientific Officer, stated the company aimed to develop an oral therapy with an “efficacy, safety and tolerability profile that is similar to that of an injectable single-acting GLP-1.”
In the 40-week study, individuals with Type 2 diabetes were randomized to receive one of three doses of orforglipron or placebo. A1C reductions ranged from 1.3% to 1.6% across the orforglipron groups, compared to a 0.1% decrease in the placebo arm, meeting the primary endpoint.

Novo Nordisk previously reported A1C reductions of 1.4% to 1.6% after 30 weeks of dosing with semaglutide. In Lilly’s Phase 2 trial, orforglipron achieved reductions of up to 2.1% at 26 weeks, though the highest dose used in that study was not carried into Phase 3.
Weight loss was a key secondary endpoint. Patients on orforglipron lost between 4.7% and 7.9% of their body weight after 40 weeks, with the highest dose group losing an average of 7.3 kg from a mean baseline of 90.2 kg. In comparison, patients on semaglutide in Novo’s trial lost up to 4.7 kg from baseline weights up to 96.9 kg.
Skovronsky previously noted that Lilly anticipates less weight loss in people with diabetes compared to those with obesity, a trend observed across the GLP-1 class. The Phase 2 study for orforglipron reported weight loss of up to 10.1 kg in 26 weeks.
Regarding safety, the most common adverse events reported were diarrhea (up to 26%), nausea (18%), and indigestion (20%). For comparison, Novo’s Phase 3 trial of semaglutide showed rates of nausea and diarrhea at 20% and 9%, respectively.

This Phase 3 readout is the first in a broader clinical program for orforglipron. Lilly anticipates additional data from five Type 2 diabetes studies and two obesity trials. Two of the obesity trials are expected to read out in the third quarter of 2025. The company plans to seek regulatory approval for obesity this year, with Type 2 diabetes submissions targeted for 2026.

The late-stage research of Bristol Myers’ heart disease medication falls short of its primary objectives

Editorial Team — Thu, 17 Apr 2025 19:42:23 +0000

Bristol Myers Squibb disclosed that its drug stavartanate did not successfully improve functional capacity or symptom intensities in heart disease patients, thus failing to reach the primary study targets.
Mavacamten received testing in adults suffering from the non-obstructive form of hypertrophic cardiomyopathy (nHCM), which represents a genetic heart condition featured by heart muscle wall thickening.
The disease HCM affects one out of every twenty adults around the world, while standing as the main identified reason for sudden cardiac death among healthy young Americans, based on government statistics. Camzyos represents a medication previously approved by the U.S. to treat obstructive hypertrophic cardiomyopathy, which creates heart ventricle blockage.

The trial outcome indicates problems with clinical benefit demonstration for less severe patient groups, according to BMO Capital Markets’ analyst Evan Seigerman, as it intensifies pressure for positive developments in upcoming events to move the BMY performance forward.
The clinical trial assessment revealed no safety warnings had appeared to the drug manufacturer. Camzyos carries a warning label with a boxed note due to heart failure risks, according to the strict provisions from the Food and Drug Administration.
The clinical research involved 580 symptomatic patients with nHCM and incorporated their self-reported questionnaire to monitor their medical status, including both symptom occurrence and physical-social constraints.
During 48 weeks of treatment, Mavacamten did not enhance exercise capacity among patients according to peak oxygen use measurements in the study. The company indicated that it will publish comprehensive trial results aimed at scientific experts at a future date.

Pfizer Decides Against Pursuing Lead Obesity Asset Amid Liver Safety Concerns

Editorial Team — Wed, 16 Apr 2025 16:32:00 +0000

Pfizer said that it had discovered a possible instance of medication-induced liver impairment and, as a result, would no longer be investing in the manufacturing of its oral GLP-1 medicine danuglipron.

According to a note from BMO Capital Markets, Pfizer is starting all over, even though danuglipron isn’t the only asset that it holds in relation to obesity.

As per Pfizer, the patient who had liver damage during the dose-optimization trials had no symptoms, and the side effect went away after they stopped using danuglipron. According to the pharmaceutical company, the total incidence of liver enzyme increases in over 1,400 individuals treated so far is comparable to other authorized medicines in this class.

Having said that, after reviewing the material – including all of the clinical data gathered so far – and discussing it with the regulators, Pfizer still decided to part ways with danuglipron.

Now that danuglipron is no longer being developed, Pfizer only has the oral GIP analog PF-07976016, which is in the second phase of clinical trials for obesity, to rely on. The research is scheduled to initially conclude in December 2025, as reported in a federal clinical trials registry.

Danuglipron, like other medications in its class, such as Wegovy and Zepbound, supports the body’s reaction to blood sugar increases by increasing insulin production by targeting and stimulating the GLP-1 receptor. Danuglipron helps reduce hunger and appetite by reducing gastric emptying as well.

In spite of its well-defined system of action, danuglipron has had difficulties in demonstrating its clinical efficacy. In December 2023, Pfizer issued the halting of danuglipron testing as a bi-daily tablet after the observation of elevated adverse effect rates in a Phase IIb trial. As many as 73% of treated individuals reported nausea, while around 25% and 47% had diarrhea and vomiting, respectively.

Pfizer disclosed that the rate of discontinuation due to adverse events exceeded 50% across all dosages of danuglipron.

In July 2024, the pharmaceutical company said that it had modified the formulation of danuglipron and will proceed with its development as a once-daily tablet. This action reinstated danuglipron to Phase I trials, although the setback seemed to have little impact on the firm’s dedication to weight reduction initiatives.

During the January 2025 J.P. Morgan Healthcare Conference, CEO Albert Bourla reaffirmed Pfizer’s commitment to obesity treatment and announced the recruitment of additional experts for decision-making. However, he moderated investors’ expectations regarding danuglipron, expressing considerable caution about the asset.

In a note released Monday, analysts stated, “VK2735 could offer Pfizer a rare opportunity to reestablish not only a mere presence in obesity, but also a leading position beyond” the current Novo Nordisk/Eli Lilly duopoly.”

Danuglipron is not Pfizer’s first unsuccessful weight-loss medication. In June 2023, the firm discontinued lotiglipron, another GLP-1 treatment, which it had been evaluating for obesity and type 2 diabetes. Lotiglipron was linked to liver safety concerns, including increased transaminase levels.