EbolaCov: A Phase IV, Single-centre, Single-blinded, Randomized Controlled Trial to Assess Safety and Immunogenicity of rVSVΔG-ZEBOV-GP Vaccination When Dosed Concurrent With mRNA COVID-19 Vaccine Booster Doses in Healthy African Adults

Concurrent vaccination scheduling for key target populations in Rwanda, such as healthcare workers, may confer significant advantages in the provision of vaccine coverage to several infectious diseases. This is a phase IV vaccine trial that looks to establish if two licenced vaccines, the rVSVΔG-ZEBOV-GP vaccine for protection against Ebola virus and messenger ribonucleic acid (mRNA) COVID vaccine for protection against SARS-CoV-2 virus, given concurrently to self selected healthy adult volunteers confers an acceptable safety profile and immunogenicity response.

Start Date01 Oct 2024

Sponsor / Collaborator

University of Birmingham

[+2]

NCT06126822 / Not yet recruitingPhase 3IIT

Safety and Immunogenicity of Ervebo® and Zabdeno® Booster Vaccines Against Ebola Virus Following Previous Vaccination With the Zabdeno/Mvabea® or Ervebo® Vaccine Schedules in DRC: a Mix-and-match Phase II RCT

The goal of this randomized controlled trial is to investigate whether individuals in DRC previously vaccinated with Zabdeno/Mvabea® or Ervebo® vaccine schedules against Ebola virus can be safely and adequately boosted with homologous or heterologous vaccine schedules.
Participants will be randomized to receive either a homologous or heterologous vaccine schedule and will be asked to come to the clinic at prespecified timepoints over a period of 6 months to collect blood samples for comparison of immunological responses against Ebola virus between both schedules. Safety and tolerability of the vaccines will be evaluated by recording Adverse Events (AE's) and grading physical and vital signs evaluations.

Start Date01 Oct 2024

Sponsor / Collaborator-

NCT05959421 / Not yet recruitingPhase 3IIT

Durability of Immunity Induced by the Ebolavirus Vaccine VSV-EBOV and As-sessment of a Booster Dose for Pre-Exposure Prophylaxis in Individuals at Potential Occupational Risk for Ebolavirus Exposure

This study is a multi-center, open label, randomized phase 3b trial to assess the durability of Immunity induced by the Ebolavirus Vaccine VSV-EBOV ( with or without booster vaccination) in individuals at potential occupational risk for ebolavirus exposure

Start Date01 Sep 2024

Sponsor / Collaborator

Universitätsklinikum Hamburg-Eppendorf

[+3]

100 Clinical Results associated with rVSV-ZEBOV

100 Translational Medicine associated with rVSV-ZEBOV

100 Patents (Medical) associated with rVSV-ZEBOV

170

Literatures (Medical) associated with rVSV-ZEBOV

01 Nov 2024·The Lancet Microbe

Safety and immunogenicity of a delayed booster dose of the rVSVΔG-ZEBOV-GP vaccine for prevention of Ebola virus disease: a multicentre, open-label, phase 2 randomised controlled trial

Article

Author: Khurana, Surender ; Maljkovic Berry, Irina ; Kuhn, Jens H ; Moir, Susan L ; Marron, Lindsay C B ; Bhadelia, Nahid ; Dighero-Kemp, Bonnie ; Langley, Joanne M ; Hewlett, Angela L ; DuChene, Alain ; Lane, H Clifford ; Rouphael, Nadine ; Raabe, Vanessa N ; Neaton, James D ; Teitelbaum, Marc ; McLellan, Susan L F ; Dozier, Nelson C E ; Davey, Richard T ; McConnell, Rosemary ; Collins, Gary L ; Kurtz, Jonathan R ; Grubbs, Gabrielle ; Poliquin, Guillaume ; Mulligan, Mark J ; Brown, Shawn K ; Hensley, Lisa E

BACKGROUNDrVSVΔG-ZEBOV-GP is the first approved vaccine with clinical efficacy against Ebola virus disease. Although a seroprotective threshold has not been defined for those at occupational risk of exposure, the current vaccine strategy is to attain a sustained high level of antibody titres. The aim of this trial was to explore the effects of delayed boosting upon both the height and duration of antibody titres following primary immunisation.METHODSIn this open-label phase 2 randomised controlled trial, we compared antibody titres at month 36 in participants who had received a homologous booster dose at month 18 following primary immunisation with those who had received no booster. From Oct 25, 2016, to Jan 29, 2020, healthy adults aged 18 years or older deemed at occupational risk of exposure to Ebola virus due to laboratory work, clinical duties, or travel to an active endemic region were recruited from four hospital clinics in the USA and one hospital clinic in Canada and received primary vaccination with 2×10⁷ plaque-forming unit per mL of VSVΔG-ZEBOV-GP. 18 months later, individuals who consented and were still eligible were randomly assigned 1:1 to receive either a homologous booster dose or no booster. Study visits for safety and serial blood collections for antibody titres were done on enrolled participants at months 0, 1, 3, 6, 12, 18, 19, 24, 30, and 36. Through July, 2021, a web-based application was used for randomisation, including assignments with schedules for each of the five sites using mixed permuted blocks. The trial was not masked to participants or site staff. The primary endpoint was a comparison of geometric mean titres (GMTs) of anti-Ebola virus glycoprotein IgG antibody at month 36 (ie, 18 months after randomisation) for all randomly assigned participants who completed the 36 months of follow-up (primary analysis cohort). Investigators were aware of antibody titres from baseline (enrolment) through month 18 but were masked to summary data by randomisation group after month 18. This study is registered with ClinicalTrials.gov (NCT02788227).FINDINGSOf the 248 participants who enrolled and received their primary immunisation, 114 proceeded to the randomisation step at month 18. The two randomisation groups were balanced: 57 participants (24 [42%] of whom were female; median age was 42 years [IQR 35-50]) were randomly assigned to the booster group and 57 (24 [42%] of whom were female; median age was 42 years [IQR 36-51]) to the no-booster group. Of those randomly assigned, 92 participants (45 in the booster group and 47 in the no-booster group) completed 36 months of follow-up. At 18 months after primary immunisation, GMTs in the no-booster group increased from a baseline of 10 ELISA units (EU)/mL (95% CI 7-14) to 1451 EU/mL (1118-1882); GMTs in the booster group increased from 9 EU/mL (6-16) to 1769 EU/mL (1348-2321). At month 19, GMTs were 31 408 EU/mL (23 181-42 554) for the booster group and 1406 EU/mL (1078-1833) for the no-booster group; at month 36, GMTs were 10 146 EU/mL (7960-12 933) for the booster group and 1240 EU/mL (984-1563) for the no-booster group. Accordingly, the geometric mean ratio (GMR) of antibody titres had increased almost 21-fold more in the booster versus no-booster group at 1 month after booster administration (GMR 20·6; 95% CI 18·2-23·0; p<0·0001) and was still over 7-fold higher at month 36 (GMR 7·8; 95% CI 5·5-10·2; p<0·0001). Consistent with previous reports of this vaccine's side-effects, transient mono-articular or oligo-articular arthritis was diagnosed in 18 (9%) of 207 primary vaccination recipients; after randomisation, arthritis was diagnosed in one (2%) of 57 participants in the no-booster group. No new cases of arthritis developed after booster administration. Four serious adverse events occurred following randomisation: one (epistaxis) in the booster group and three (gastrointestinal haemorrhage, prostate cancer, and tachyarrhythmia) in the no-booster group. None of the serious adverse events was judged attributable to the booster vaccination assignment.INTERPRETATIONIn addition to no new safety concerns and in marked contrast to earlier trials evaluating short-term boosting, delaying a rVSVΔG-ZEBOV-GP booster until month 18 resulted in an increase in GMT that remained several-fold above the no-booster group GMT for at least 18 months. These findings could have implications for defining the optimal timing of booster doses as pre-exposure prophylaxis in populations at ongoing risk for Ebola virus exposure.FUNDINGThe Division of Intramural Research and the Division of Clinical Research of the National Institute of Allergy and Infectious Diseases at the US National Institutes of Health, Canadian Immunization Research Network through the Public Health Agency of Canada, Canadian Institutes of Health Research, and the US Defense Threat Reduction Agency.

01 Oct 2024·Journal of Infection

Replication, safety and immunogenicity of the vectored Ebola vaccine rVSV-ΔG-ZEBOV-GP in a sub-Saharan African paediatric population: A randomised controlled, open-label trial in children aged 1-12 years living in Lambaréné, Gabon

Article

Author: Kavishna, Ranmali ; Agnandji, Selidji T ; Velavan, Thirumalaisamy P ; Harandi, Ali M ; Musangomunei, Fungai P ; Olubiyi, Bisola F ; Rothenberger, Sylvia ; Nakaya, Helder I ; Siegrist, Claire-Anne ; Kabwende, Anita L ; Medaglini, Donata ; Kokou, Kossiwa ; Mahmoudou, Saidou ; Engler, Olivier ; Alabi, Ayodele ; Nakka, Sravya S ; Kremsner, Peter G ; Bie-Ondo, Juste C

BACKGROUNDUnlike adults, children experienced stronger and longer vector replication in plasma and shedding in saliva following rVSVΔG-ZEBOV-GP vaccination. The resulting risks of immunosuppression or immune hyperactivation leading to increased Adverse Events (AEs) and altered antibody responses are concerns that have been addressed in the present manuscript.METHODSChildren aged 1-12 years living in Gabon received either rVSVΔG-ZEBOV-GP (ERVEBO®) vaccine or the varicella-zoster virus (VZV) vaccine (VZV). The concentration of rVSVΔG vector in blood and saliva, the occurrence of AEs up to day 28; the anti-rVSVΔG-ZEBOV-GP and anti-VZV IgG antibody titres, neutralising and avidity functions of anti-rVSVΔG-ZEBOV-GP by day 365; were assessed in serum. (PACTR202005733552021) FINDINGS: In the rVSVΔG-ZEBOV-GP group, 70% and 7% of children had > 0 copies/ml of rVSVΔG respectively in plasma by day 3 and in saliva by day 14 after vaccination, with no detection on day 28. Significantly higher but transient AEs occurred in the rVSVΔG-ZEBOV-GP group. Both vaccines induced seroconversion on day 28 and sustainable IgG antibody titres by day 365. Avidity and neutralisation functions of the anti-rVSVΔG-ZEBOV-GP antibodies peaked at day 28 and were maintained by day 365.INTERPRETATIONThe replication and shedding do not affect the favourable risk-benefit balance of the rVSVΔG-ZEBOV-GP in children.FUNDINGThis trial is funded by the Innovative Medicines Initiative 2 (IMI 2) Joint Undertaking (grant number: 116068). The Biomedicine and Social Sciences research team of CERMEL is funded by the European and Developing Countries Clinical Trials Partnership (EDCTP-TMA-SF-1946-VARSAF).

01 Sep 2024·Vaccine

Knowledge, attitudes, and practices and long-term immune response after rVSVΔG-ZEBOV-GP Ebola vaccination in healthcare workers in high-risk districts in Uganda

Article

Author: Harmon, Jessica ; Mulei, Sophia ; Haberling, Dana L ; Spiropoulou, Christina ; Cossaboom, Caitlin M ; Waltenburg, Michelle A ; Kainulainen, Markus H ; Twongyeirwe, Sam ; Bergeron, Eric ; Makumbi, Issa ; Muruta, Allan ; Baluku, Jimmy ; Whitesell, Amy ; Lutwama, Julius J ; Shoemaker, Trevor ; Montgomery, Joel M ; Balinandi, Stephen ; Driwale, Alfred ; Nyakarahuka, Luke ; Kyondo, Jackson ; Klena, John D ; Tumusiime, Alex

BACKGROUNDThe rVSVΔG-ZEBOV-GP Ebola vaccine (rVSV-ZEBOV) has been used in response to Ebola disease outbreaks caused by Ebola virus (EBOV). Understanding Ebola knowledge, attitudes, and practices (KAP) and the long-term immune response following rVSV-ZEBOV are critical to inform recommendations on future use.METHODSWe administered surveys and collected blood samples from healthcare workers (HCWs) from seven Ugandan healthcare facilities. Questionnaires collected information on demographic characteristics and KAP related to Ebola and vaccination. IgG ELISA, virus neutralization, and interferon gamma ELISpot measured immunological responses against EBOV glycoprotein (GP).RESULTSOverall, 37 % (210/565) of HCWs reported receiving any Ebola vaccination. Knowledge that rVSV-ZEBOV only protects against EBOV was low among vaccinated (32 %; 62/192) and unvaccinated (7 %; 14/200) HCWs. Most vaccinated (91 %; 192/210) and unvaccinated (92 %; 326/355) HCWs wanted to receive a booster or initial dose of rVSV-ZEBOV, respectively. Median time from rVSV-ZEBOV vaccination to sample collection was 37.7 months (IQR: 30.5, 38.3). IgG antibodies against EBOV GP were detected in 95 % (61/64) of HCWs with vaccination cards and in 84 % (162/194) of HCWs who reported receiving a vaccination. Geometric mean titer among seropositive vaccinees was 0.066 IU/mL (95 % CI: 0.058-0.076).CONCLUSIONAs Uganda has experienced outbreaks of Sudan virus and Bundibugyo virus, for which rVSV-ZEBOV does not protect against, our findings underscore the importance of continued education and risk communication to HCWs on Ebola and other viral hemorrhagic fevers. IgG antibodies against EBOV GP were detected in most vaccinated HCWs in Uganda 2─4 years after vaccination; however, the duration and correlates of protection warrant further investigation.

News (Medical) associated with rVSV-ZEBOV

14 Nov 2024

·www.prnewswire.com

INOVIO Reports Third Quarter 2024 Financial Results and Recent Business Highlights

New immunology data for INO-3107 supporting proposed mechanism of action presented at several recent conferences Data showed ability of INO-3107 to induce an antigen-specific cytotoxic T cell response against HPV-6 and HPV-11 and drive recruitment of T cells into airway tissues and papilloma Data showed INO-3107 induced expansion of new clonal T cells that infiltrate airway tissues and correspond with reduction of surgeries for RRP patients observed in Phase 1/2 trial Continued progress on preparing regulatory submissions for INO-3107 All non-device BLA modules on track for completion by end of 2024 BLA submission remains targeted for mid-2025 PLYMOUTH MEETING, Pa., Nov. 14, 2024 /PRNewswire/ -- INOVIO (NASDAQ: INO), a biotechnology company focused on developing and commercializing DNA medicines to help treat and protect people from HPV-related diseases, cancer, and infectious diseases, today announced its financial results for the third quarter of 2024 and provided an update on recent company developments. "We continue to be focused on advancing INO-3107 and delivering a non-surgical option to RRP patients. Toward this goal, we expect to have all non-device modules for our BLA completed by year end, while in parallel we continue to implement the plan to resolve the previously announced manufacturing issue with the single-use array component of the device. With this progress, we continue to target the submission of our BLA in mid-2025," said Dr. Jacqueline Shea, INOVIO's President and Chief Executive Officer. "Our development of INO-3107 is supported by a growing body of research that collectively points to INO-3107's potential to be an important therapeutic option for all RRP patients regardless of the severity of their disease. We recently presented new immunology data highlighting the ability of INO-3107 to induce new populations of T cells that travel to the airway tissue and papilloma and correspond with clinical benefit. We've also presented our full safety and efficacy data, demonstrating that INO-3107 was shown to be well tolerated and have clinical benefit in the Phase 1/2 trial. Additionally, by the end of year, we anticipate announcing long-term clinical durability data. We continue to believe INO-3107 has the potential to become the preferred choice for the broadest number of RRP patients, healthcare providers and payors, if approved." Recent Business Highlights Lead Candidate, INO-3107 – Recurrent Respiratory Papillomatosis INOVIO's primary focus is driving toward the regulatory approval and commercialization of its lead product candidate, INO-3107. Recent progress includes advancing preparations for submitting the BLA, targeted for mid-2025, and announcing the following new data. New Immunology Data: INOVIO presented additional immunology data demonstrating the ability of INO-3107 to induce antigen-specific T cell responses against HPV-6 and HPV-11 and drive recruitment of those T cells into airway tissues and papilloma of RRP patients, which could potentially slow or eliminate papilloma regrowth. These data were presented at the American Association for Cancer Research (AACR) Special Conference and at the 36th International Papillomavirus Conference. In totality, this new data showed: Induction of T cell responses specific to HPV-6 and HPV-11, including cytotoxic CD8+ T cells, which were still present at week 52, indicating an establishment of memory response Expansion of clonal T cell populations in peripheral blood, including induction of new clonal T cell populations that travelled to airway or papilloma tissue Induction of inflammatory responses in papilloma and airway tissue, including: - Interferon, cytokine and chemokine signaling - Adaptive and innate immune cell infiltration, with emphasis on T cells Cytotoxic signatures of infiltrated T cells in papilloma/airway tissue, providing direct evidence of increased overall T cell infiltration compared to pre-treatment T cell infiltration in airway tissues of clinical responders were predominantly new T cell clonal populations not detectable prior to INO-3107 treatment Clinical activity not impacted by immunosuppressive papilloma microenvironment Full Safety and Efficacy Data: INOVIO presented its full safety and efficacy data set for the Phase 1/2 trial in which INO-3107 was shown to be well tolerated and have clinical benefit. Of the 32 patients in the trial, 26 patients, or 81%, experienced a decrease in the number of surgical interventions in the year after treatment when compared to the year before treatment. These data were presented at both the International Society of Vaccines Conference and the Fall Voice Conference. In the trial, the overall clinical response (OCR) was 81%, with 26 of the 32 enrolled patients experiencing a decrease in the number of surgical interventions in the year after INO-3107 administration compared to the prior year, including 28% (9/32) that required no surgical intervention (i.e., complete response, or CR) during or after the dosing window. Further, 44% (14/32) of patients had a partial response (PR), measured by a reduction of at least 50%, but less than 100%, in the number of surgeries when compared to the prior year. The overall response rate (ORR) of patients (CR+PR) was therefore 72% (23/32). Other key data points presented include: INO-3107 was shown to be well tolerated and have clinical benefit - 41% (13/32) of patients reported a treatment-related Adverse Event (AE) - No treatment-related AEs greater than Grade 2 severity were reported - Most frequent treatment-related AE's reported were injection site pain (31%) and fatigue (9%) Modified Derkay-Pransky severity scores improved from baseline to the end of 52-week trial INO-3107 induced durable cellular responses and generated T cells against HPV-6 and HPV-11 Other Pipeline Updates INOVIO continued to advance plans for a Phase 3 trial of INO-3112 as a potential treatment for HPV-related oropharyngeal squamous cell carcinoma also known as throat cancer, through ongoing conversations with regulators in the European Union. This trial is anticipated to be conducted in North America and Europe. Previously, the FDA had indicated alignment with the proposed trial design, which was developed in conjunction with a trial steering committee. INOVIO continued to advance its plans for a Phase 2 trial of INO-4201 as a heterologous boost to the FDA licensed Ebola vaccine, Ervebo®. A meeting is scheduled with the FDA in the fourth quarter of 2024 to discuss the proposed Phase 2 trial design. Patients continue to be dosed in the GBM-001 trial with INO-5401. Regeneron and Inovio have discussed that an appropriate next step would be a controlled Phase 2 trial. Third Quarter 2024 Financial Results Cash, Cash Equivalents and Short-term Investments: As of September 30, 2024, cash, cash equivalents and short-term investments were $84.8 million compared to $145.3 million as of December 31, 2023. Research and Development (R&D) Expenses: R&D expenses for the three months ended September 30, 2024, were $18.7 million compared to $15.5 million for the same period in 2023. The increase in R&D expenses was primarily the result of overall higher drug manufacturing costs and higher engineering professional and outside services related to device development, offset by lower employee and consultant compensation, including non-cash stock-based compensation, among other variances. General and Administrative (G&A) Expenses: G&A expenses were $8.6 million for the three months ended September 30, 2024 compared to $9.9 million for the same period in 2023. The decrease in G&A expenses was primarily related to a decrease in employee compensation, including non-cash employee and consultant stock-based compensation, and a decrease in legal expenses, among other variances. Total Operating Expenses: Total operating expenses were $27.3 million for the three months ended September 30, 2024, compared to $35.9 million for the same period in 2023. During the three months ended September 30, 2023, the company recognized a non-cash goodwill impairment charge of $10.5 million. Net Loss: Net loss for the three months ended September 30, 2024 was $25.2 million, or $0.89 per basic and diluted share, compared to net loss of $33.9 million, or $1.52 per basic and diluted share, for the three months ended September 30, 2023. Shares Outstanding: As of September 30, 2024, INOVIO had 26.1 million common shares outstanding, 2.1 million pre-funded warrants outstanding, and 29.9 million common shares outstanding on a fully diluted basis, after giving effect to the exercise, vesting, and conversion, as applicable, of its outstanding pre-funded warrants, options, restricted stock units and convertible preferred stock. INOVIO's balance sheet and statement of operations are provided below. Additional information is included in INOVIO's quarterly report on Form 10-Q for the quarter ended September 30, 2024, which can be accessed at: . Cash Guidance INOVIO estimates its cash runway to extend into the third quarter of 2025. This projection includes an operational net cash burn estimate of approximately $24 million for the fourth quarter of 2024. These cash runway projections do not include any further capital-raising activities that INOVIO may undertake. Conference Call / Webcast Information INOVIO's management will host a live conference call and webcast with slides at 4:30 p.m. ET today to discuss INOVIO's financial results and provide a general business update. The live webcast and replay may be accessed by visiting INOVIO's website at . About INOVIO's DNA Medicines Platform INOVIO's DNA medicines platform has two innovative components: precisely designed DNA plasmids, delivered by INOVIO's proprietary investigational medical device, CELLECTRA®. INOVIO uses proprietary technology to design its DNA plasmids, which are small circular DNA molecules that work like software the body's cells can download to produce specific proteins to target and fight disease. INOVIO's proprietary CELLECTRA® delivery devices are designed to optimally deliver its DNA medicines to the body's cells without requiring chemical adjuvants or lipid nanoparticles and without the risk of the anti-vector response historically seen with viral vector platforms. About INOVIO INOVIO is a biotechnology company focused on developing and commercializing DNA medicines to help treat and protect people from HPV-related diseases, cancer, and infectious diseases. INOVIO's technology optimizes the design and delivery of innovative DNA medicines that teach the body to manufacture its own disease-fighting tools. For more information, visit . Contact: Media: Jennie Willson (267) 429-8567 [email protected] Investors: Thomas Hong (267) 440-4298 [email protected] Forward-Looking Statements This press release contains certain forward-looking statements relating to our business, including our plans to develop and commercialize DNA medicines and our expectations regarding our research and development programs, including the planned initiation and conduct of clinical trials and the availability and timing of data from those trials, the planned submission of a BLA in mid-2025, expectations regarding INO-3107's potential to be an important therapeutic option for RRP patients and the preferred choice of RRP patients, healthcare providers and payors, as well as plans for discussions with regulatory authorities, the planned commercial launch of INO-3107 if regulatory approval is obtained, and expectations with respect to our cash resources into the third quarter of 2025 and expected cash burn for the fourth quarter of 2024. Actual events or results may differ from the expectations set forth herein as a result of a number of factors, including uncertainties inherent in pre-clinical studies, clinical trials, product development programs and commercialization activities and outcomes, the availability of funding to support continuing research and studies in an effort to prove safety and efficacy of electroporation technology as a delivery mechanism or develop viable DNA medicines, our ability to support our pipeline of DNA medicine products, the ability of our collaborators to attain development and commercial milestones for products we license and product sales that will enable us to receive future payments and royalties, the adequacy of our capital resources, the availability or potential availability of alternative therapies or treatments for the conditions targeted by us or collaborators, including alternatives that may be more efficacious or cost effective than any therapy or treatment that we and our collaborators hope to develop, issues involving product liability, issues involving patents and whether they or licenses to them will provide us with meaningful protection from others using the covered technologies, whether such proprietary rights are enforceable or defensible or infringe or allegedly infringe on rights of others or can withstand claims of invalidity and whether we can finance or devote other significant resources that may be necessary to prosecute, protect or defend them, the level of corporate expenditures, assessments of our technology by potential corporate or other partners or collaborators, capital market conditions, the impact of government healthcare proposals and other factors set forth in our Annual Report on Form 10-K for the year ended December 31, 2023, our Quarterly Report on Form 10-Q for the quarter ended September 30, 2024, and other filings we make from time to time with the Securities and Exchange Commission. There can be no assurance that any product candidate in our pipeline will be successfully developed, manufactured, or commercialized, that the results of clinical trials will be supportive of regulatory approvals required to market products, or that any of the forward-looking information provided herein will be proven accurate. Forward-looking statements speak only as of the date of this release, and we undertake no obligation to update or revise these statements, except as may be required by law. SOURCE INOVIO Pharmaceuticals, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Clinical ResultPhase 2Vaccine

22 Aug 2024

·www.fiercepharma.com

First real-world analysis of Merck's Ebola vaccine reveals 84% effectiveness during DRC outbreak

Merck delivered hundreds of thousands of doses of its then-unapproved vaccine to the Democratic Republic of Congo to help to address the 2018 Ebola outbreak. When a deadly outbreak of the Ebola virus spread through the Democratic Republic of Congo in 2018, Merck’s then-unapproved vaccine was quickly deployed to help address the crisis and provide protection to hundreds of thousands of recipients. Now, four years after that epidemic ended, a new analysis offers a clearer picture on the vaccine’s real-world effectiveness. For the study, the researchers looked at data collected from Ebola treatment centers to gauge the real-world effectiveness of the vaccine during the 2018-20 outbreak in the DRC, according to an article published in The Lancet Infectious Diseases. The study, which is the first to evaluate the real-world effectiveness of "widespread use" of the vaccine, showed that Merck's shot was 84% effective against the virus in people who were infected 10 or more days after vaccination.The "test-negative analysis" determined the vaccine's effectiveness by weighing the likelihood of Ebola-positive patients being vaccinated or unvaccinated during the period. The study framework has also been used to weigh vaccine effectiveness in other viral diseases such as influenza and COVID-19, the study authors noted, as the usual standard of running randomized controlled trials can present ethical concerns in the context of a virus epidemic. Before this study, the only efficacy stats on Merck’s vaccine were estimated in a phase 3 study that utilized the ring vaccination strategy in a smaller number of participants. Ring vaccination is a viral mitigation strategy that involves vaccinating those in contact with someone with confirmed exposure.That study, which occurred during a massive outbreak in West Africa from 2014 to 2016, put the vaccine's efficacy rate at an estimated 100%. The real-world outcomes findings weren’t expected to match that perfect result, the authors of the new study noted.Merck's vaccine, branded as Ervebo, is recommended by the World Health Organization's (WHO's) Strategic Advisory Group of Experts on Immunization for those at risk of Ebola exposure during outbreaks. The shot was provided in the DRC during the 2018-20 epidemic through an expanded access framework. The vaccine won approval in Europe and the U.S. in 2019. Last year, the FDA expanded its use to cover use in people 12 months and older, versus its previous approval only in adults. More than 300,000 people received the vaccine during the 2018 DRC outbreak via the ring vaccination approach, including pregnant women and infants. That outbreak had a fatality rate of 66%, with 2,287 reported Ebola-related deaths. The largest Ebola outbreak in history took place in West Africa a few years prior, killing more than 11,300 people.Elsewhere on the Ebola countermeasures front, Regeneron markets a triple-combo antibody treatment for the virus, while Johnson & Johnson and Bavarian Nordic also have a WHO-prequalified vaccine regimen. Merck, for its part, was the first to score approval for an Ebola vaccine. The company took over the shot from original developer National Microbiology Laboratory and licensee NewLink Genetics during the West African outbreak in 2013.

Drug ApprovalClinical ResultVaccinePhase 3

08 Aug 2024

·www.prnewswire.com

INOVIO Reports Second Quarter 2024 Financial Results and Recent Business Highlights

PLYMOUTH MEETING, Pa., Aug. 8, 2024 /PRNewswire/ -- INOVIO (NASDAQ:INO), a biotechnology company focused on developing and commercializing DNA medicines to help treat and protect people from HPV-related diseases, cancer, and infectious diseases, today announced its financial results for the second quarter of 2024 and provided an update on recent company developments. "We continue to make progress with our lead candidate, INO-3107, which has the potential to significantly improve the lives of patients with RRP. We expect all non-device related elements of our BLA package to be completed by year end and our pre-BLA meeting last week with the FDA provided us with confidence that we remain on the right track for the regulatory submission. However, as part of the testing process required for BLA submission, we've recently identified a manufacturing issue with the single use disposable administration component of our device that we believe is resolvable, but will take additional time to rectify," said Dr. Jacqueline Shea, INOVIO's President and Chief Executive Officer. "We're taking corrective steps to address the issue, and while we have not altered our ultimate expectations for INO-3107 to be a potentially transformative therapeutic option for RRP patients that could be the first DNA medicine approved for use in the United States, we now expect to be able to submit the BLA in mid-2025. We will continue to work hard to advance all other elements necessary for INO-3107's success, including working to initiate our confirmatory trial, advancing plans for our redosing trial, making key regulatory progress in Europe and the U.K., and continuing commercial preparations to be launch-ready if we receive approval. These efforts will help maintain the momentum that's carried us from Breakthrough Therapy Designation to BLA preparation in less than a year." "We've continued making progress in other key areas of our business as well," Dr. Shea continued. "We submitted our Phase 3 clinical plans for INO-3112 to European regulatory authorities, anticipate re-submitting our Phase 2 clinical plans for our Ebola booster vaccine candidate, INO-4201, to the FDA in the third quarter, and are continuing discussions with partners to advance INO-5401 as a potential treatment for GBM. We also welcomed Steve Egge to our leadership team as our Chief Commercial Officer. Steve brings extensive launch experience in HPV-related diseases, cancer, immunology and rare diseases and I know his commercial expertise will be invaluable as we work to advance INO-3107 and our other promising candidates." Recent Business Highlights INO-3107 – Recurrent Respiratory Papillomatosis (RRP) INOVIO continued advancing preparations for submitting its BLA under the FDA's Accelerated Approval pathway, including holding a pre-BLA meeting with the FDA, advancing development of all BLA modules, trial site preparations and ongoing commercial readiness plans. However, INOVIO has identified an issue related to the manufacturing of the single use disposable administration component of the CELLECTRA® device that will delay its BLA submission, now anticipated in mid-2025. INOVIO is working to rectify the issue as quickly as possible, using all resources available, and expects to provide further updates at the next quarterly report. INO-3107 was designated an innovative medicine as part of the U.K.'s Innovative Licensing and Access Pathway (ILAP). The designation, called an Innovation Passport, is the first step on a development pathway that offers enhanced access to regulators and development tools that could accelerate the timeline for achieving U.K. regulatory approval. INO-3107 received an Advanced Therapy Medicinal Product (ATMP) Certification from the European Medicines Agency's Committee for Advanced Therapies (CAT) after review of chemistry, manufacturing and controls (CMC) and nonclinical data. This certification confirms that the data reviewed complies with the standards that would be used to evaluate a European marketing-authorization application. Immunology data for INO-3107 has been accepted at the following fourth quarter conferences: Fall Voice, a leading conference for clinicians focused on vocal disorders 36th International Papillomavirus Conference, a platform for sharing cutting-edge international HPV research International Society for Vaccines Annual Congress INO-3112 – Oropharyngeal Squamous Cell Carcinoma (OPSCC) INOVIO submitted its Phase 3 trial design for INO-3112 to European regulatory authorities. The proposed multi-center Phase 3 trial will investigate INO-3112 in combination with LOQTORZI as a potential treatment for oropharyngeal squamous cell carcinoma (OPSCC). INOVIO plans to conduct the trial in Europe and North America. INOVIO received positive feedback on this study protocol from the FDA in the first quarter of 2024. The manufacturing issue with the single use disposable administration component of the device that is impacting INO-3107 will also need to be resolved before we can commence the Phase 3 trial with INO-3112. The combination of INO-3112 with LOQTORZI has the potential to address a substantial unmet need in patients with HPV-16 and -18 related high-risk throat cancer. The Phase 3 study will investigate whether LOQTORZI can help amplify the tumor-infiltrating abilities of the antigen-specific T cells generated by INO-3112. INO-3112 is a DNA medicine candidate containing a DNA plasmid encoding HPV-16/-18 E6 and E7 antigens combined with another DNA plasmid encoding IL-12 as an immune activator. LOQTORZI is an FDA-approved PD-1 inhibitor approved for the treatment of recurrent locally advanced/metastatic nasopharyngeal carcinoma. INO-4201 for Ebola INOVIO anticipates submitting its revised protocol to the FDA for a Phase 2/3 clinical trial with INO-4201 as a heterologous boost to the FDA licensed Ebola vaccine, Ervebo, in the third quarter. INOVIO previously announced positive results from a Phase 1b clinical trial evaluating INO-4201 as a booster in healthy adult participants who previously received a single injection of Ervebo. In the trial, INO-4201 was well-tolerated and boosted humoral responses in 100% (36 of 36) of treated participants. Operational and Financial Updates INOVIO appointed Steve Egge as Chief Commercial Officer to lead the company's commercial strategy and operations as it prepares to launch INO-3107. Mr. Egge has extensive experience in many different therapeutic areas, including immunology and vaccines, HPV, and rare disease. Mr. Egge spent 20 years at Merck, where he held a number of different commercial leadership roles, including leading Merck's HPV Vaccines Franchise and serving as Chief Marketing Officer for the Vaccine Division. Over the course of his career, he has overseen or contributed to more than 13 commercial product launches. INOVIO welcomes his expertise, particularly in creating and growing new therapeutic areas as well as driving market share in competitive markets. INOVIO strengthened its balance sheet with an offering of common stock and pre-funded warrants in April 2024; net proceeds from the offering, after deducting underwriting discounts and commissions and offering expenses, were $33.2 million. Second Quarter 2024 Financial Results Cash, Cash Equivalents and Short-term Investments: As of June 30, 2024, cash, cash equivalents and short-term investments were $110.4 million compared to $145.3 million as of December 31, 2023. Research and Development (R&D) Expenses: R&D expenses for the three months ended June 30, 2024, were $23.1 million compared to $23.7 million for the same period in 2023. The slight decrease in R&D expenses was primarily the result of overall lower drug manufacturing costs and lower employee and consultant compensation, including non-cash stock-based compensation, among other variances. General and Administrative (G&A) Expenses: G&A expenses were $10.2 million for the three months ended June 30, 2024 compared to $13.5 million for the same period in 2023. The decrease in G&A expenses was primarily related to a decrease in employee compensation, including non-cash employee and consultant stock-based compensation, and a decrease in legal expenses, among other variances. Total Operating Expenses: Total operating expenses were $33.3 million for the three months ended June 30, 2024, compared to $37.3 million for the same period in 2023. Net Loss: INOVIO's net loss for the three months ended June 30, 2024 was $32.2 million, or $1.19 per basic and diluted share, compared to net loss of $35.5 million, or $1.61 per basic and diluted share, for the three months ended June 30, 2023. Shares Outstanding: As of June 30, 2024, INOVIO had 26.0 million common shares outstanding, 2.1 million pre-funded warrants outstanding, and 29.9 million common shares outstanding on a fully diluted basis, after giving effect to the exercise, vesting, and conversion, as applicable, of its outstanding pre-funded warrants, options, restricted stock units and convertible preferred stock. INOVIO's balance sheet and statement of operations are provided below. Additional information is included in INOVIO's quarterly report on Form 10-Q for the quarter ended June 30, 2024, which can be accessed at: . Cash Guidance INOVIO estimates its cash runway to extend into the third quarter of 2025. This projection includes an operational net cash burn estimate of approximately $28 million for the third quarter of 2024. These cash runway projections do not include any further capital-raising activities that INOVIO may undertake. Conference Call / Webcast Information INOVIO's management will host a live conference call and webcast with slides at 4:30 p.m. ET today to discuss INOVIO's financial results and provide a general business update. The live webcast and replay may be accessed by visiting INOVIO's website at . About INOVIO's DNA Medicines Platform INOVIO's DNA medicines platform has two innovative components: precisely designed DNA plasmids, delivered by INOVIO's proprietary investigational medical device, CELLECTRA®. INOVIO uses proprietary technology to design its DNA plasmids, which are small circular DNA molecules that work like software the body's cells can download to produce specific proteins to target and fight disease. INOVIO's proprietary CELLECTRA® delivery devices are designed to optimally deliver its DNA medicines to the body's cells without requiring chemical adjuvants or lipid nanoparticles and without the risk of the anti-vector response historically seen with viral vector platforms. About INOVIO INOVIO is a biotechnology company focused on developing and commercializing DNA medicines to help treat and protect people from HPV-related diseases, cancer, and infectious diseases. INOVIO's technology optimizes the design and delivery of innovative DNA medicines that teach the body to manufacture its own disease-fighting tools. For more information, visit . Contact: Media: Jennie Willson (267) 429-8567 [email protected] Investors: Thomas Hong (267) 440-4298 [email protected] Forward-Looking Statements This press release contains certain forward-looking statements relating to our business, including our plans to develop and commercialize DNA medicines and our expectations regarding our research and development programs, including the planned initiation and conduct of clinical trials and the availability and timing of data from those trials, the planned submission of a BLA towards the middle of 2025, plans for discussions with regulatory authorities, the planned commercial launch of INO-3107 if regulatory approval is obtained, and expectations with respect to our cash resources into the third quarter of 2025 and expected cash burn for the third quarter of 2024. Actual events or results may differ from the expectations set forth herein as a result of a number of factors, including uncertainties inherent in pre-clinical studies, clinical trials, product development programs and commercialization activities and outcomes, the availability of funding to support continuing research and studies in an effort to prove safety and efficacy of electroporation technology as a delivery mechanism or develop viable DNA medicines, our ability to support our pipeline of DNA medicine products, the ability of our collaborators to attain development and commercial milestones for products we license and product sales that will enable us to receive future payments and royalties, the adequacy of our capital resources, the availability or potential availability of alternative therapies or treatments for the conditions targeted by us or collaborators, including alternatives that may be more efficacious or cost effective than any therapy or treatment that we and our collaborators hope to develop, issues involving product liability, issues involving patents and whether they or licenses to them will provide us with meaningful protection from others using the covered technologies, whether such proprietary rights are enforceable or defensible or infringe or allegedly infringe on rights of others or can withstand claims of invalidity and whether we can finance or devote other significant resources that may be necessary to prosecute, protect or defend them, the level of corporate expenditures, assessments of our technology by potential corporate or other partners or collaborators, capital market conditions, the impact of government healthcare proposals and other factors set forth in our Annual Report on Form 10-K for the year ended December 31, 2023, our Quarterly Report on Form 10-Q for the quarter ended June 30, 2024, and other filings we make from time to time with the Securities and Exchange Commission. There can be no assurance that any product candidate in our pipeline will be successfully developed, manufactured, or commercialized, that the results of clinical trials will be supportive of regulatory approvals required to market products, or that any of the forward-looking information provided herein will be proven accurate. Forward-looking statements speak only as of the date of this release, and we undertake no obligation to update or revise these statements, except as may be required by law. SOURCE INOVIO Pharmaceuticals, Inc.

Phase 1VaccineClinical ResultPhase 3Phase 2

100 Deals associated with rVSV-ZEBOV

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KEGG	Wiki	ATC	Drug Bank
-	rVSV-ZEBOV	J07BX	-

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Approved

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Indication	Country/Location	Organization	Date
Hemorrhagic Fever, Ebola	IS	Merck Sharp & Dohme BV	11 Nov 2019
Hemorrhagic Fever, Ebola	LI	Merck Sharp & Dohme BV	11 Nov 2019
Hemorrhagic Fever, Ebola	EU	Merck Sharp & Dohme BV	11 Nov 2019
Hemorrhagic Fever, Ebola	NO	Merck Sharp & Dohme BV	11 Nov 2019

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Indication	Highest Phase	Country/Location	Organization	Date
HIV Infections	Phase 2	CA	Merck Sharp & Dohme Corp.	01 Aug 2017
Hemorrhagic Fever, Ebola	Phase 2	-	Merck Sharp & Dohme Corp.	17 Aug 2015

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02378753 (STRIVE, Pubmed \| Emerg Infect Dis)	Phase 2/3	Pregnancy	84	rVSVΔ-ZEBOV-GP Ebola Vaccine (Immediate vaccinated women)	(nfpdksgbzu) = vakxxzzefh ugkekickew (eghoajmwnf )	-	17 Mar 2020
				rVSVΔ-ZEBOV-GP Ebola Vaccine (Unvaccinated women)	(nfpdksgbzu) = kvmcmdcmpb ugkekickew (eghoajmwnf )
NCT02269423 (V920-001, CTgov)	Phase 1	Hemorrhagic Fever, Ebola	39	Placebo+V920 (3x10^6 Plaque-forming Units (Pfu) Vaccine Cohort)	gnfmqtitep(akgsbvewuc) = nyesjjzabp umncvgsjmp (hyvewkdcnf, ynpjovpnto - joxefyptpa) View more	-	23 Oct 2019
				Placebo+V920 (2x10^7 Pfu Vaccine Cohort)	gnfmqtitep(akgsbvewuc) = icuuxzclps umncvgsjmp (hyvewkdcnf, cbzcepfswc - sdewhecayd) View more
NCT02503202 (V920-012, Pubmed \| Am J Trop Med Hyg)	Phase 3	-	1,197	rVSVΔG-ZEBOV-GP Vaccine (rVSVΔG-ZEBOV-GP (2 × 107 pfu))	tmitaxdjvd(xlnekhcjnw) = jsocrxorml pjthrfldix (ptgeutcixs )	-	30 Aug 2019
				rVSVΔG-ZEBOV-GP Vaccine (high-dose 1 × 108 pfu)	tmitaxdjvd(xlnekhcjnw) = tplucgzgno pjthrfldix (ptgeutcixs )
NCT02280408 (V920-002, CTgov)	Phase 1	Hemorrhagic Fever, Ebola	39	V920 (3x10^6 Plaque-forming Units (Pfu) Vaccine Cohort)	pkbbbbraav(xijsjxcdux) = psfxrnqkiz hpnxwgpmkv (wjgvsljeph, qhfrjxards - itwyvzpioj) View more	-	12 Jul 2019
				V920 (2x10^7 Pfu Vaccine Cohort)	pkbbbbraav(xijsjxcdux) = rysobwzoap hpnxwgpmkv (wjgvsljeph, uwrhwiphww - zpgbpwqgct) View more
NCT02503202 (V920-012, CTgov)	Phase 3	Hemorrhagic Fever, Ebola	1,197	V920 Consistency Lot A (V920 Consistency Lot A)	ieurxnadbe(qdenkgijvu) = ffrfeyjigb odfgfviqpe (oujveoeqhp, wbxecmfjxe - pgoiatvhoj) View more	-	12 Oct 2018
				V920 Consistency Lot B (V920 Consistency Lot B)	ieurxnadbe(qdenkgijvu) = knumlqqewl odfgfviqpe (oujveoeqhp, etqazrgtla - kczkyhidrk) View more
NCT02378753 (STRIVE, CTgov)	Phase 2/3	Hemorrhagic Fever, Ebola	8,651	rVSVΔG-ZEBOV (rVSVΔG-ZEBOV (Immediate Vaccination))	awskmbserx(dhphmkcbff) = pxexlkplqs htiflkvfsc (hqkaeijqnx, zprvgxwiig - brsskfxsff) View more	-	05 Apr 2018
				rVSVΔG-ZEBOV (rVSVΔG-ZEBOV (Deferred Vaccination))	awskmbserx(dhphmkcbff) = vsmgrahyia htiflkvfsc (hqkaeijqnx, gvhatyjqzv - tnhescmiso) View more
NCT02378753 (Pubmed) Manual	Phase 2/3	Hemorrhagic Fever, Ebola	992	rVSV-ZEBOV	(wekljragcf) = aayfoqyini mpzeoongwu (noidatzbtw )	Positive	08 Jul 2016
NCT02287480 (Pubmed) Manual	Phase 1/2	Hemorrhagic Fever, Ebola	51	rVSV-ZEBOV	(numrfumqhg) = No serious adverse events occurred. cybxjbykro (cmkoqpcjiv )	Positive	01 Oct 2015
				Placebo

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