09/29/2026  |  Jean-Pascal Zambaux  |  Clinical Leader

https://www.clinicalleader.com/doc/long-distance-rare-disease-trials-why-pll-landed-on-australia-and-new-zealand-0001 

Conducting clinical trials for rare diseases, such as amyotrophic lateral sclerosis (ALS), is a complex, resource-intensive process. Trial location can influence patient recruitment, site activation timelines, regulatory processes, and access to specialized clinical expertise. In rare disease trials, these factors can affect the likelihood of completing the study on time, within budget, and with robust data. For us at PLL Therapeutics, a French clinical-stage biopharmaceutical company, Australia presented a combination of operational, regulatory, and clinical research factors that supported the decision to conduct the first stage of its ALS trial there. After completing Phase 1 in Australia, we are now preparing a Phase 2a/2b trial spanning Australia and New Zealand.

The Attraction Of Australia
In less than two years, following our initial encounter with the Australian delegation’s first-ever attendance at a bio event in Boston in 2024, we set up and successfully completed stage one of our first-in-human Phase 1/2 trial of ALS in Australia.  

We were struck by the speed in which the clinical study was implemented and conducted in Australia, crediting the country’s launch in 2025 of the Australian Clinical Trials Initiative (ACTI), a national program designed to build on Australia’s strong research infrastructure and streamlined regulatory processes while attracting more international studies. ACTI promotes Australia’s clinical research capabilities overseas, coordinates trade missions, and provides practical support to biotech and pharmaceutical companies considering Australia as a trial location. The initiative aims to improve access to innovative therapies for Australian patients and generate much-needed evidence in rare diseases, rare cancers, and other conditions with limited treatment options.

Australia’s focus on clinical trials, particularly in areas such as rare diseases where specialist expertise and efficient recruitment are essential, and its research infrastructure ultimately drove our decision to conduct our studies there. The extensive support the country offered more than offset the challenges of operating from Europe.

Regulatory efficiency and speed
Speed of approval is one of the most compelling advantages of conducting a rare disease clinical trial in Australia. In contrast to the FDA and EMA, where regulatory processes can be lengthy and bureaucratic, Australia’s system was streamlined, with approvals overseen by ethics committees rather than a centralized regulatory body.

The short timelines allowed us to secure approval for both Phase 1 and 2 trials in under six months, a stark contrast to the one to two years typically taken by European or the U.S. regulators. The ethics committees’ focus on science and patient safety, and its flexibility, allowed for quicker iterations and adjustments to our study protocols without the delays experienced in more rigid systems. We valued this efficiency particularly for our rare disease study in ALS, where death occurs three to five years after onset.

R&D tax incentives
Under the ACTI scheme, Australia offers a 42% R&D tax rebate, meaning we recouped nearly half of our R&D expenditures. For biotech companies, especially those with limited budgets, this financial incentive is very attractive. The rebate applies to clinical trial costs, placing Australia among the top most cost-effective locations for conducting research.

Skilled workforce and strong knowledge base
With a highly skilled workforce, particularly in neurodegenerative diseases, such as ALS, Australia has successfully developed a network of experts, including practitioners who have transitioned from academia and hospitals to CROs. Through this network of professionals with deep knowledge in the neurodegenerative field, established relationships with hospitals, and in-depth understanding of the logistical and scientific challenges of rare disease trials, we found it highly motivating to coordinate our clinical trial in Australia.

We also value the quality and experience of their local CROs, which specialize in small-scale, high-complexity trials. We chose a CRO with prior experience in ALS and stroke trials with leadership from institutions, including the Florey Institute of Neuroscience in Melbourne.

Australia maintains a strong and skilled workforce by retaining its talent with competitive opportunities to prevent brain drain to the U.S. or Europe. In addition, the healthcare system is actively working to attract researchers and clinicians from abroad, further strengthening its expertise.

Cost-effectiveness
Beyond the R&D tax rebate, Australia enabled us to conduct clinical trials at lower operational costs compared to the U.S. and western Europe. This includes everything from site fees to staffing and logistics. We found that the country provided a comparable quality of data and execution at a fraction of the cost of conducting the trial in France or the U.S.

Regulatory framework aligned with international standards
In Australia, our clinical trial is aligned with international regulatory standards, thus making it easier to transition our trials to other regions, which we plan to do through our Australian subsidiary, PLL Tx, as the sponsor of future Phase 3 trials, to include patients in the U.S., Europe, and, potentially, China. We anticipate that Australia’s reputation for high-quality data will help simplify our path to global approvals.

Additionally, Australia’s compassionate use programs are more flexible than those in many other countries, allowing for earlier and more streamlined access to experimental therapies for patients in need.

Patient recruitment
One of the surprising advantages of conducting a clinical trial in Australia for rare diseases is the country’s high prevalence of ALS (relative to the population). While the exact reason for the higher prevalence is unclear (potential genetic factors or environmental influences), we had a ready cohort of patients to participate.

The patient criteria for our Phase 1/2 clinical trial in ALS were highly specific (e.g., patients with high levels of inflammation). Despite the narrow focus, the principal investigator estimated that ~150 patients per year in Australia met the criteria, making recruitment feasible. We witnessed the hospitals play a proactive role in identifying and referring eligible patients, leveraging their existing networks and databases.

Challenges
While Australia offers many advantages, conducting trials remotely from Europe presented unique challenges.

Logistics and coordination

Managing a trial from afar requires meticulous planning and strong local partnerships to address:

• Site selection: The CRO identified hospitals across Australia (e.g., Calvary and Alfred in Melbourne, hospitals in Brisbane – Wesley and Sydney) with the infrastructure and expertise to conduct the trial.
• Drug distribution: The CRO coordinated the supply chain for investigational products, including labeling, packaging, and shipping to local pharmacies.
• Patient monitoring: Clinical staff administered the injections to patients at the hospital. This will differ in our Phase 2a/2b studies where patients will self-administer injections at home. We will partner with a nursing service to train patients, monitor compliance, and ensure proper administration.
• Sample collection: Blood and stool samples were collected, labeled, and shipped to France for biomarker analysis. This required specialized logistics to maintain sample integrity.

Cultural and operational differences

Contrary to expectations, we experienced minimal cultural barriers. We found the ethics committees in Australia are highly organized, with each hospital or region having its own committee. These committees replace the role of centralized agencies like the TGA or ANSM for trial oversight, focusing on ethical and scientific rigor.

In managing communications, we maintain weekly meetings with the local team, and I personally travel to Australia from France four or five times per year to align on milestones, address challenges, and foster relationships with the principal investigator.

Although we established subsidiaries in Australia and New Zealand, the teams are lean. They focus more on legal and administrative activities while the CRO and local partners undertake the bulk of clinical activities.

Future Outlook
We are looking ahead to conducting our Phase 2a/2b trials in ALS in the Pacific region, at sites in Australia, including Perth, as well as Auckland, New Zealand, where international clinical trials are rarely conducted. The Phase 2a/2b studies are designed to reflect our unique approach of targeting pre-symptomatic patients to protect motor neurons rather than treating them after damage has occurred, making our approach a first in ALS research.

Phase 2a will include 30 patients randomized into three arms (placebo + two dosages) with the primary endpoints being restoration of gut integrity (a key focus of our therapy) and reduction of inflammation. Phase 2b will enroll a minimum of 60 patients for an extended follow-up beyond the initial six-month Phase 2a trial and seek to explain the Phase 2a endpoints to include broader ALS progression metrics.

Lessons Learned Down Under
What would we do differently? Not much. The combination of Australia’s regulatory efficiency, skilled workforce, and financial incentives have shown to be a winning formula for us. For other biotech companies considering trials in Australia, here are some key takeaways:

• Leverage local expertise: Our partnership with local CRO Alithea Lifesciences, which has disease-specific experience, was critical. Their prior ALS and stroke trial experience streamlined site selection, patient recruitment, and logistics.
• Cherish the speed: Australia’s six-month approval timeline is a major advantage, as long as thorough high-quality documentation has been prepared.
• Take advantage of incentives: The 42% R&D tax rebate significantly reduces costs. Work with local advisors to optimize financial strategy.
• Build relationships: Regular travel and in-person meetings with principal investigators and ethics committee fosters trust and alignment.
• Plan for logistics: Long-distance trials require robust logistics for drug distribution, patient monitoring, and sample collection. Partnering with specialized service providers (nursing services, shipping, etc.) is essential.

Australia has been far more than just a location for us. Rather, the country quickly became a strategic partner that enabled rapid progress, high-quality data, and a pathway to global expansion. We consider Australia’s combination of regulatory efficiency, financial incentives, skilled workforce, and cost-effectiveness a compelling case for biotech companies to conduct complex trials.

About The Author:
Jean-Pascal Zambaux, cofounder and CEO of PLL Therapeutics, has a 30+ year career in the pharmaceutical and biotech industry. He created Disposable-Lab, a CMO specializing in producing injectable drugs for clinical trials, where he served as CEO between 2008 and 2018, and successfully ran the first pharma company to use a single-use grade A isolator for fill ‘n’ finish. He holds a Doctorate in Pharmacy (PharmD) earned from the University of Paris and the University of Reims, Champagne-Ardenne.

09/29/2026  |  VHIO (Vall d'Hebron Institut d'Oncology)

https://vhio.net/2026/09/29/blood-could-serve-as-a-main-source-for-finding-cancer-specific-proteins-needed-to-develop-personalized-treatment/ 

A blood-based approach could enable personalized immunotherapy without the need for a tumor biopsy

Cancer neoantigens and neoantigen-specific T cells were identified from patient blood samples by analyzing circulating tumor DNA (ctDNA) and immune cells, respectively, and they largely matched those found through traditional tumor tissue biopsy in many patients, according to research published in Cancer Discovery, a journal of the American Association for Cancer Research (AACR).

“Neoantigens, which are proteins produced by cancer cells, make tumors easily recognizable to the immune system, prompting it to mount an immune response against the cancer cells expressing these neoantigens,” said Alena Gros, PhD, senior author of the study and group leader of the Tumor Immunology and Immunotherapy Group at the Vall d’Hebron Institute of Oncology (VHIO) in Barcelona, Spain.

Because neoantigens are not found on normal cells, targeting them may be an effective and safe strategy for cancer immunotherapy, Gros explained. She noted that researchers are developing personalized immunotherapies that target neoantigens, including cancer vaccines and T cell-based therapies.

A crucial step in developing personalized immunotherapies is identifying the neoantigens and neoantigen-specific T cells that are present within each patient’s tumor. Doing so can also help identify patients likely to benefit from immunotherapy, since the presence of these biomarkers indicates that a tumor may be immunogenic, she added.

“Currently, clinicians identify neoantigens and neoantigen-specific T cells by analyzing tumor tissue collected through a biopsy or other surgical procedure. However, many patients do not have easily accessible tumors or are not healthy enough to undergo an invasive biopsy or surgery,” Gros said.

As a less invasive alternative to these procedures, Gros and colleagues examined whether they could identify neoantigens and neoantigen-specific T cells using only patient blood. They reasoned that the DNA shed by cancer cells into the bloodstream, known as ctDNA, could provide insights into the mutations present within the tumor.

The researchers isolated and sequenced ctDNA from the blood samples of six patients with metastatic melanoma, breast cancer, head and neck cancer, or colorectal cancer. They were unable to isolate ctDNA from the blood of two additional patients, one with breast cancer and the other with head and neck cancer, which Gros explained is consistent with the fact that some tumors shed very little DNA.

Gros and colleagues analyzed the ctDNA sequences to identify neoantigens and compared the results to those obtained from conventional tumor tissue analysis from the same six patients. They found that, across all six patients, the ctDNA analysis identified 63.25% to 97.4% of the neoantigens identified by standard tumor tissue analysis.

Further, ctDNA analysis identified many neoantigens not found by standard tumor tissue analysis. The ability to detect neoantigens that could not be found in resected tumor tissue suggests that a blood-based approach may provide a more representative view of the different neoantigens found in patients with metastatic disease, Gros explained. “Patients with advanced disease have tumors in different organs, so a biopsy of one tumor may not capture the neoantigens found in other lesions,” she said. “By accessing the blood, we can find neoantigens that are present in other lesions, as well as T cells against these other neoantigens, giving us a better understanding of the tumor heterogeneity and the systemic immune response happening in the patient.”

Additionally, they found that T cells isolated from the blood samples of six out of eight patients recognized and reacted to neoantigens identified by ctDNA and/or tumor tissue.

To evaluate the applicability of ctDNA for neoantigen discovery in a broader population, Gros and colleagues expanded their analysis to a separate cohort of 69 patients with various types of metastatic solid tumors. ctDNA was detectable in 32 of 69 patients (46%) across solid tumor types, suggesting that a blood-based approach to neoantigen discovery may be possible in roughly half of patients. Among 17 patients with colorectal cancer, ctDNA was detectable in 14 (82.4%), including in patients with mismatch repair-deficient tumors, which typically express more neoantigens and are typically treated with immunotherapies which target neaontigens.

“Our study suggests that blood-based neoantigen identification has the potential to replace or complement the traditional tissue-based approach in many patients and cancer types,” said Gros. “Because blood is easier and faster to collect than tumor tissue, this approach could reach patients who have inaccessible tumors or are unable to undergo a biopsy. It could also allow patients to begin treatment sooner because they wouldn’t have to wait for a biopsy.”

Gros also pointed to the potential of using the blood-based approach to examine how neoantigens and patient immune responses change during treatment, which could help clinicians monitor treatment responses and provide insights into tumor evolution and treatment resistance.

Limitations of the study include the small patient population and the low prevalence of certain cancer types within the population. Gros noted that additional validation in larger patient cohorts is needed before the approach could be widely used in the clinic.

The study was supported by Merck; Comprehensive Program of Cancer Immunotherapy and Immunology (II) supported by the BBVA Foundation; Instituto de Salud Carlos III; Asociación Española Contra el Cáncer; La Fundació la Marató de TV3; Ministerio de Ciencia, Innovación y Universidades; and Generalitat de Catalunya (Government of Catalonia). Gros has received personal fees from Roche and has patents for E-085-2013/0 (licensed and with royalties paid from Intima Bioscience Inc. and Geneius Biotechnology, Inc) and E-149-2015/0 (licensed and with royalties paid from Intima Bioscience Inc., Intellia Therapeutics Inc., and Tailored Therapeutics, LLC).
 

09/28/2026  |  Access newswire

https://www.accessnewswire.com/newsroom/en/healthcare-and-pharmaceutical/clinical-trial-of-the-oral-drug-nv-387-to-treat-ebola-has-started-enr-1227696 

NanoViricides, Inc. (NYSE American:NNVC) (the "Company"), a clinical stage leader developing antiviral drugs that viruses cannot escape, announces that its Phase II Clinical Trial of NV-387 Oral Gummies as a Treatment for the Current Bundibugyo Ebolavirus and other Ebola viruses in the Democratic Republic of Congo ("DRC") has started enrolling and dosing patients at an Ebola Treatment Center in the Ituri province.

This clinical trial is registered in the Pan African Clinical Trials Registry (pactr.samrc.ac.za) database. The unique identification number for this clinical trial is PACTR202608748555077.

The clinical trial is entitled with a descriptive title: "An adaptive, multi-centre Phase IIA/IIB clinical trial of NV-387 oral gummies plus optimised supportive care in adults with Ebola virus disease (Bundibugyo or other orthoebolaviruses): a single-arm safety and dose run-in (Phase IIA) followed by a randomised, controlled, open-label efficacy evaluation with independent blinded-endpoint adjudication (Phase IIB)." Prof. Patrick de Marie Chimusa Katoto is listed as the principal investigator to lead this clinical trial, as previously announced by the Company.

Enrollment and dosing has begun in the Phase IIA part on September 23, 2026 or thereabouts. The Phase IIA part is designed to arrive at a NV-387 dosing protocol that is safe and well tolerated within the context of the disease symptoms and severity. We are aiming for maximum feasible dosing while avoiding non-tolerable adverse events, because of the high fatality rate of the Ebola Bundibugyo Virus Disease (EVD/BVD), in order to make maximum impact on the infecting virus. The dosage protocol arrived at in this Phase IIA part, as stratified by disease severity, will be fixed for use across patients in the Phase IIB part. The Phase IIB part is designed to evaluate safety tolerability and effectiveness of the NV-387 Oral Gummies treatment on the Ebolavirus infection.

"Our DRC Team and the CRO are committed to contribute to produce the best results for the patients, hoping to maximize survival," said Anil R. Diwan, PhD, President of the Company, adding, "NV-387 as an oral treatment could make a great contribution to combatting the current and future Ebola outbreaks if found to be effective as a treatment."

The severity of EVD/BVD is simplistically stratified into (a) a Dry Stage, wherein patient symptoms include fever, aches, pains, and fatigue that can be confused with many other infections; and (b) a Wet Stage, wherein explosive vomiting and diarrhea, the hallmark clinical symptoms, are presented. The Wet Stage may progress to (c ) a Critical Stage, which requires intensive care, with a high fatality rate. Unexplained bleeding may occur in the Wet Stage or Critical Stage. The Dry Stage or the Wet Stage may progress into Recovery Stage. The patient's recovery is slow. The patient is infectious, i.e., can transmit the viral infection to others from the dry stage until full recovery.

Currently, a clinical trial called "PARTNERS" was started as of July 2, 20261 to evaluate two drugs that both require delivery by infusion. Approximately 300 patients have already been enrolled in this trial across four groups, namely (i) Infusion of a monoclonal antibody cocktail, MBP134, (ii) Infusion of Remdesivir, (iii) Infusion of MBP134 plus Infusion of Remdesivir, and (iv) a control group with local standard of care.

Infusions are inherently unscalable for the extent of the current ebola outbreak in the resource-poor areas in DRC. Additionally, infusion treatment also increases risks to health care workers such as needle-sticks, as well as due to patient handling and possible blood exposure.

NV-387 is currently the only orally administered drug in clinical trials to the best of our knowledge, and this is why medical professionals in the field are looking forward to success in the clinical trial of NV-387.

Oral NV-387 was compared with Intravenously given Remdesivir given in animal studies of a lethal coronavirus infection model when NV-387 was originally developed as a treatment for COVID-19. NV-387 Oral was found to be superior in extending survival of the lethally infected animals when compared to Remdesivir I.V. in this study. Therefore, the Company believes that NV-387 oral drug can be reasonably expected to provide superior activity compared to at least remdesivir infusion that is already in the PARTNERS clinical trial.

Antibodies are easily overcome by viruses in the field, as was experienced during the COVID-19 pandemic. All antibody drugs that received emergency use approvals lost efficacy within a few months due to mutations in the SARS-CoV-2, an RNA virus. Ebola Bundibugyo is an RNA virus with likely similar rates of mutation. It remains to be seen if and how long MBP134 remains effective during the current Ebola outbreak, even if found to be effective and approved, for use.

The Bundibugyo virus is highly unlikely to escape NV-387, unlike in the case of antibodies such as MBP134. This is because NV-387 mimics a portion of the cell surface that is essential for all Ebola viruses to cause productive infection, no matter how different they are.

"Comparing NV-387 to currently available therapeutics under study leads us to rationally anticipate at least partial success in the proposed clinical trial," said Dr. Diwan, warning, "However, it is the data from the clinical trial that will tell us if NV-387 is effective and can become an important pillar in response to this Ebola Outbreak Crisis in DRC."

The current Ebola Virus Disease (EVD) caused by the Bundibogyo ebolavirus (BDBV) is now the largest ever ebola outbreak, as well as the fastest growing ebola outbreak in DRC.

As of September 23, 2026, there have been 7,890 confirmed cases, 3,799 confirmed deaths, and 1,966 confirmed recoveries in DRC, according to the WHO daily report2. In comparison, as of August 14, 2026, there were reported 4,945 confirmed cases and 2,325 confirmed deaths due to this virus. The crude fatality rate (crude CFR)3 is about 48% .

The actual probability of an infected person dying is about 67%, with about 1/3rd of patients recovering in DRC (ibid #2 footnote).

This Ebola outbreak is now the fastest growing ebola outbreak in the world. Additionally, it is also possibly the deadliest ebola outbreak. At this rate, the current outbreak is on track to exceed the worst ever ebola zaire outbreak in West Africa in 2014-20164. In that outbreak, 28,616 cases and 11,310 deaths were recorded across Guinea, Liberia and Sierra Leone, according to the World Health Organization.

Schools have reopened normally in the Ebola affected regions across DRC, despite the well understood risk of transmission in schools. Teaching and implementing hygienic measures such as use of hand sanitizers and frequent hand washing is expected to minimize risk, enabling the children to have in-class education. The alternative of remote learning is very difficult to implement in resource-poor environments, and risks the children's education itself. If cases occur, schools would be shut down. The risk is high, particularly because the crude case fatality rate (CFR) in children is at 60%, much greater than the CFR for adults at sub-50%5.

Additionally, health care workers (HCW) are at high risk, despite personal protective equipment, because of close contact with the patients. At least 43 HCWs have died from Ebola and at least 160 have contracted the disease6.

The need for an oral drug to combat this disease is thus obvious. An oral drug to treat patients, to prevent contacts from contracting the disease, and to keep healthcare workers safe, is sorely needed to combat this outbreak. There is a tremendous urgency to validate a drug that works against this ebolavirus in short and decisive clinical trials for minimizing further spread by treating patients and for saving lives. Om Sai CRO, in consultation with renowned scientists in DRC, has designed the Phase II clinical trial with this particular objective.

In contrast, in the PARTNERS clinical trial, infusions of antibody cocktails and of remdesivir are being tried. This trial will require over 1,000 patients to be treated and may not yield results for several months. A similar large collaborative clinical trial effort in the West Africa 2014-2016 outbreak resulted in US FDA approval of two antibody drugs only specifically for EBOV Zaire, which are not deemed to be useful in the current outbreak without further clinical trials.

Three different vaccines are also expected to enter into clinical trials for efficacy within months, according to the WHO7. Ervebo, a vaccine developed for Ebola Zaire, is being deployed in a research protocol to health care workers. Its efficacy against BDBV needs to be evaluated in a clinical trial, according to WHO.

As of now, there is practically no risk from this Ebola outbreak for the USA, according to the CDC. The US has imposed strict travel restrictions to avoid any possible introduction of the ebola virus into the USA. The CDC is intimately involved in the Ebola response with 150 personnel deployed within DRC for the efforts (ibid #1).

NanoViricides has retained Om Sai Clinical Research Private Limited, India, (Om Sai CRO) as the CRO for this Phase II clinical trial for Ebola in DRC. Om Sai CRO has been instrumental in putting together the team with Prof. Katoto and other renowned experts and with support from the University of Bukavu and in the Ebola-affected region to lead and execute the clinical trial of NV-387 Oral Gummies as a Treatment for Ebola viruses in DRC.

As the Ebola outbreak continues to expand, several limitations on travel are being instated. There are also limitations on availability of resources such as PPE and diagnostic kits, which are compounded by the travel and other restrictions. These on-ground situations have caused delays in our efforts, and we anticipate such delays to continue due to the tenuous outbreak situation.

This Ebola outbreak continues to increase in spread and is now present in at least six provinces in DRC and threatening South Sudan8. More concerning is the fact that over 80% of new cases are outside of known contact lists, leading to the projection that the extent of the outbreak is at least two times or more larger than the reported confirmed cases. Additionally, Ebola is now found to have spread into displacement camps that host over 4.4 million displaced persons due to internal warfare, adding another high risk population pool with poor drinking water, sanitation and medical resources to further fuel this outbreak, according to the UN New Service.

There is no approved Treatment or Vaccine for the new variant of the Bundibugyo Ebolavirus (BDBV) that is causing the current rapidly expanding outbreak of the Ebolavirus Disease (EVD) in DRC. The rare Bundibugyo strain of Ebola virus causing the current outbreak appears to be its new variant, likely freshly introduced from some animal source9, such as fruit bats.

"Although this antiviral (Remdesivir) proved to be ineffective at targeting the Zaire Ebolavirus, there remains hope that it could have some benefit against the Bundibugyo virus, particularly if used in combination with MBP-134," according to an article in Forbes explaining the "PARTNERS" clinical trial by the WHO organized collaboration10. The article also notes that MBP134 contains two separate antibodies designed to, taken together, recognize multiple Ebola species.

Antibodies are highly specific to a particular strain of the virus and usually are not very effective against variants of the same virus that arise in the field. Viruses also escape antibodies readily by mutations in the field.

NV-387 is a broad-spectrum antiviral that mimics the host-side features that the virus requires, and is likely to be effective against Ebola viruses because they use the same host-side feature mimicked by NV-387.

NV-387 Oral Gummies is a drug product readily delivered orally. It does not even require swallowing effort or water, because it dissolves in the mouth by itself, simplifying delivery for even sick individuals with swallowing difficulties.

This oral delivery is an important feature that puts NV-387, a broad-spectrum antiviral, as being superior to the other approaches.

"Only safe and effective broad-spectrum antiviral drugs like NV-387 that can effectively tackle most viral infections will enable the world to combat viruses and defend the global population in the war against known and unknown nanoscopic enemies that are viruses," commented Dr. Diwan, adding, "Today, NV-387 is the only drug in clinical development with such broad-spectrum potential that promises to combat diverse epidemics like Mpox and Ebola, to the best of our knowledge."

While there is currently minimal risk of Ebola in the USA, the CDC's mathematical models suggested this Central African outbreak could grow to 10,000 to 20,000 cases and 2,000 to 4,000 deaths within just three months, rivaling the largest outbreak to date in 2014-201611. Unfortunately, the outbreak appears to be even more aggressive than the CDC model, with over 2,000 deaths in less than three months, over 4,000 confirmed cases, and over 10,000 estimated total cases12.

The outbreak which was declared a Public Health Emergency of International Concern ("PHEIC") by the WHO on May 17, 2026, continues to rapidly expand, outpacing containment efforts. The outbreak arose in a high traffic region bordering the Democratic Republic of Congo (DRC), with travel contacts to Uganda, and South Sudan and with 11 more nations in Africa at risk13.

NV-387 is a broad-spectrum antiviral that mimics the host-side feature called heparan sulfate proteoglycan (HSPG) that over 90-95% of human pathogenic viruses require for infecting cells. No matter how much the virus changes in the field, it continues to use HSPG, and therefore it cannot escape the drug NV-387. In contrast, Remdesivir is a small molecule inhibitor of the viral RDRP enzyme needed for making copies of the viral genome, and the virus can possibly escape by small number of mutations.

All Ebola viruses utilize HSPG as the attachment receptor prior to gaining entry into the cell. Thereafter, followed by entry into the cell inside endosomes, the ebolavirus surface glycoprotein is substantially degraded, opening up its site for binding to its cognate receptor called NPC1, thereby entering into the cytoplasm where the next steps in its replication begin.

Thus there is a strong rationale that NV-387 could be highly effective against Ebola virus infections, not just Bundibugyo, but also the Sudan and other viruses for which there are no treatments.

All previous anti-Ebola efforts have been focused on vaccines and antibodies14. This has led to approval of therapies that are specific to the Ebolavirus Zaire strain only, albeit with limited effectiveness. This leaves out all other filoviruses of consequence: Sudan, Marburg, and the more rare Bundibugyo with no treatment or vaccine.

In contrast, if NV-387, as a broad-spectrum antiviral, is found to be effective against the Bundibugyo virus, it will likely be effective against all ebolaviruses and possibly all filoviruses; that would be a game changer for pandemic preparedness.

The case fatality rate of ebolaviruses has generally been approximately 50% in recent outbreaks, with improvements in care, including hydration therapy, corticosteroids, and other usual symptomatic treatments. Ebola viruses spread via bodily fluid secretions including fomites/sputum, as well as semen/genital secretions. Ebola virus can remain in survivors even as many as 965 days after the disease without symptoms, and can transmit through bodily secretions, suggesting possible latency. Many recent outbreaks have been ignited as a result of such reawakened-transmitted virus from a survivor. Sexual transmission was documented even as late as 482 days after disease. This persistence and possible latency of ebolavirus in immune-privileged organs (e.g. brain, eyes, gonads, where antibodies are not operative) makes it a uniquely serious threat for global transmission and sustained outbreaks.

At present, BDBV has been consistently demonstrating high crude CFR of 48% in DRC. Therefore, BDBV is of great concern as a potential pandemic disease. However, it is believed that ebolaviruses do not transmit via respiratory droplets or aerosols and rather require extensive contact with bodily fluids of an infected person. In addition, within DRC and internationally, certain protective quarantine measures for travel from the outbreak areas have been implemented.

Therefore, currently there is no apparent threat of a global pandemic.

An irony is that because of the high case fatality rate (CFR) approaching 50%, the spread of ebolaviruses remains rather limited. If a variant emerges with a reduced CFR, say in the range of 5-15%, the potential threat of global pandemic from such an outbreak would increase substantially.

With ever-increasing global travel, local outbreaks such as ebola can quickly travel far and wide potentially causing global pandemics, as was the case with COVID-19, if not caught in time. It is not feasible to produce a new vaccine and a new set of antibody drugs to combat every possible virus. Even if vaccines and antibodies are produced, the virus would escape by generating variants, as the world has witnessed during the COVID-19 pandemic.

The US Government is active in ensuring that suspected or confirmed ebolavirus cases do not enter the general population in the USA. To this end, travel from DRC has been restricted, with pre-travel quarantine requirements imposed, and suspect travelers are directed to screening at specific airports and may be further quarantined.

Travelers going to and from Central Africa need to constantly check travel restrictions as well as travel limitations in light of these changing outbreak conditions.

09/28/2026  |  Krishma Shah  |  The Clinical Trial Vanguard

https://www.clinicaltrialvanguard.com/clinical-trial-ops-brief/when-the-primary-endpoint-moves-after-283-patients-are-already-in/ 

The amendment landed on February 10, 2025. By that point, 283 patients had already been enrolled in the intra-arterial alteplase post-thrombectomy trial, 214 of them had completed or were eligible for 90-day follow-up, and the primary outcome was changing. No interim analyses had run. No treatment-group data had broken the blind. The authors of the JAMA reply are clear on those points, and those distinctions matter for data integrity. But none of that clarity reduces the operational weight of what just landed in every site coordinator’s inbox.

A primary outcome amendment at month 12, after the majority of enrolled patients are already in or past the follow-up window, is not a paperwork event. It is a cascade that touches IRB submissions, patient notification decisions, source document alignment, monitoring visit scope, and query resolution logic, often simultaneously, often with no additional timeline accommodation from the sponsor.

The Cascade No One Budgets For
Start with the IRB. Under 21 CFR 312.30, any change that significantly affects the scientific quality of a Phase 2 or 3 protocol requires a formal protocol amendment submission. A primary outcome change almost certainly meets that threshold. The FDA’s reconsent requirement activates when the amendment could affect a participant’s willingness to continue in the study. For a trial measuring a clinical outcome like the modified Rankin Scale score, changing how that outcome is defined, assessed, or weighted is exactly the kind of modification a participant might reasonably want to know about before their next scheduled visit.

That puts every site coordinator in a familiar bind. The amendment is approved by the sponsor’s internal governance on a specific date. The IRB submission goes in. The IRB review timeline for a substantial amendment varies by board and review pathway, often extending weeks, and longer if the board requires full committee review. During that window, sites are in operational limbo: following the old protocol, aware that the new one is coming, and unable to act on the change they already know is approved. Any patient who shows up for a 90-day follow-up visit during that gap gets assessed under the old outcome definition, because the IRB has not yet cleared the new one. The data that comes out of those visits then has to be reconciled against the amended protocol after the fact, and the query cycle that follows is not cheap.

Published cost data from a study of 836 Phase I-IV protocols puts the median direct cost of implementing a substantial amendment at $141,000 for a Phase II protocol and $535,000 for a Phase III protocol. Those figures capture sponsor-side costs. They do not capture the site-level cost: coordinator hours spent re-reviewing the protocol, re-training on the amended outcome assessment, updating source document templates, preparing reconsent scripts, and fielding queries generated by the transition period. Sites absorb that cost against a budget that was negotiated months or years earlier, against a per-visit payment structure that did not anticipate the amendment workload.

The 57% amendment rate across that same dataset means this is not an edge case. More than half of protocols change substantially at some point during execution. Nearly half of those changes were judged avoidable. What that number represents at the site level is thousands of coordinator hours, thousands of IRB submission cycles, and thousands of reconciliation queries that sites fund out of existing budgets while sponsors track the cost as a line item in their protocol management systems.

What the Timing Tells You
The authors are transparent about why the amendment happened when it did: emerging randomized evidence and the established use of blinded mRS score assessment changed the calculus on clinical relevance and interpretability. That is a legitimate scientific rationale. The operational question is separate from whether the rationale is sound.

Well into a trial’s execution, with 283 patients enrolled, is not early. It is not a pre-enrollment correction. It is a mid-execution change that lands on sites that have already built their follow-up workflows, trained their assessors, and in many cases already collected primary outcome data from patients who completed the 90-day window. The DEFUSE 3 trial offers a useful reference point: when the DEFUSE 3 protocol was modified in June 2017 following the DAWN trial results, the amendment triggered enrollment suspension and an NIH-requested interim analysis that ultimately ended the trial early. That is an extreme outcome, but it illustrates the chain: external evidence shifts, protocol changes, and the operational consequences are immediate and structural.

The intra-arterial alteplase study amendment, by contrast, was handled without interim analysis, without breaking the blind, and with enrollment presumably continuing through the change. Those are meaningful protections for data integrity. But sites operating through that window had to manage the transition in real time, often without the kind of protocol amendment training visit that a change of this magnitude warrants. Sites I work with consistently report that amendment communications arrive as a revised protocol document and a cover memo, with the expectation that the site team will self-train and update their own SOPs. When the amendment touches something as central as the primary outcome, that expectation is worth examining.

What Changes on Monday
For sponsor clinops teams, the operational discipline question is whether the amendment plan includes explicit site activation steps, not just IRB submission tracking. A primary outcome amendment needs a defined site readiness checklist: updated source document templates distributed before the IRB approval date so sites can adapt them immediately upon clearance, a brief training attestation for all outcome assessors, and a clear protocol for handling patients who are assessed during the IRB review gap. Without those three elements in place before the amendment package goes to the IRB, the site-level execution risk falls entirely on the coordinator.

For site teams, the immediate priority when a primary outcome amendment arrives is to pull every patient currently in or approaching the follow-up window and map their assessment dates against the IRB review timeline. If any assessments are scheduled to occur during the gap period, that needs to be flagged to the sponsor and CRA before the visit happens, not after. The deviation risk from assessing under the wrong outcome definition is real, and the cost of a protocol deviation at this stage of a trial, with data already accumulated, is higher than the cost of a brief delay to get the assessment right.

Across our network, the sites that manage amendment transitions without generating a wave of queries and deviations are the ones that treat the IRB submission date as a workflow trigger, not a waiting period. They start updating templates, briefing assessors, and mapping patient schedules the day the amendment package goes in, so they can activate within 24 hours of IRB approval rather than scrambling to catch up.

The authors of this JAMA reply handled the scientific rationale for their amendment correctly. The operational industry still needs to catch up to what that kind of mid-stream decision actually costs the sites executing it, and build the infrastructure to absorb that cost before the next 283-patient amendment arrives.

References

1. JAMA, “Intra-Arterial Alteplase After Successful Thrombectomy for Acute Ischemic Stroke, Reply”
2. PubMed, “Cost and impact of substantial protocol amendments in clinical trials” (836 Phase I-IV protocols dataset)
3. eCFR, 21 CFR 312.30, Protocol Amendments
4. Helsedirektoratet, DEFUSE 3 Trial Protocol and Amendment Documentation
    

09/28/2026  |  Robert Herriman  |  Outbreak News Today

https://outbreaknewstoday.substack.com/p/cuba-phase-3-clinical-trial-of-jusvinza 

Specialists from the Center for Genetic Engineering and Biotechnology (CIGB) presented the results of a Phase 3 clinical trial on the use of Jusvinza in patients with arthritis following Chikungunya virus infection.

The is already used in Cuba to treat conditions such as rheumatoid arthritis, Guillain-Barré syndrome, and COVID-19.

For this Phase 3 clinical trial involving the subcutaneous administration of Jusvinza to patients with Chikungunya-induced arthritis, 300 individuals were selected—90% of whom were in the chronic stage of the disease. Starting March 16, 2026, they received nine doses of the Cuban drug at a clinic in the La Lisa municipality and at the Diez de Octubre Clinical-Surgical Hospital.

Chikungunya epidemic risk: A call to action

We wanted to see if the results at week 12 remained consistent with previous studies; indeed, the therapeutic effect was validated as sustained. By week 12, among a total of 260 patients, an additional 16 had shown satisfactory progress, resulting in an 87% response rate. Furthermore, over 95% of patients achieved a reduction in disability—moving to a state of low disability or no disability—a figure that reached over 97% by week 12.

These Phase 3 trials on the use of Jusvinza—leveraging its anti-inflammatory properties in post-Chikungunya patients—were preceded by two earlier trials: one conducted in Matanzas and another in Havana. Both of those studies also yielded encouraging results.

Chikungunya continues in Cuba in early 2026

Across all three trials, the initial hypothesis was conclusively confirmed. Jusvinza has been shown to elicit a favorable clinical response in patients, successfully reducing both painful and inflammatory joint symptoms; this enables patients to maintain their daily routines, return to work, and improve their quality of life. Crucially, throughout the drug’s clinical development for this indication, an appropriate safety profile was demonstrated, with no serious or moderate adverse events—only mild ones, most of which did not require conventional treatment to manage.

Jusvinza is an innovative immunomodulatory and anti-inflammatory peptide developed by the Center for Genetic Engineering and Biotechnology (CIGB) in Cuba.

It is a synthetic 27-amino-acid peptide (originally designated as CIGB-814 or CIGB-258) derived from a human heat shock protein.

It acts as an immunoregulator that controls hyperinflammation without inducing general immunosuppression.