Novocure Presents Final Safety, Efficacy Results from Phase 2 Liver Cancer Trial

 Disease control rate was 76% with 9.5% objective response in a patient population with poor prognosis and limited exposure to study treatments

In patients who completed at least 12 weeks of Tumor Treating Fields treatment, disease control rate was 91% with 18% objective response

Novocure plans to proceed with phase 3 pivotal trial in liver cancer incorporating Tumor Treating Fields together with standard treatments, including immunotherapy

Novocure (NASDAQ: NVCR) today announced final results from its phase 2 pilot HEPANOVA trial in liver cancer testing the safety and efficacy of Tumor Treating Fields (TTFields) together with sorafenib for the treatment of advanced hepatocellular cancer. In 21 evaluable patients, the disease control rate was 76% in a patient population with poor prognosis and limited exposure to study treatments. The objective response rate for the intent-to-treat population was 9.5%. In patients who completed at least 12 weeks of TTFields treatment, the disease control rate was 91% with an objective response rate of 18%. The final HEPANOVA results will be presented at the virtual ESMO World Congress on Gastrointestinal Cancer on July 1.

The HEPANOVA trial enrolled 27 patients with unresectable hepatocellular cancer. Fourteen of the 27 patients, or 52%, had a Child-Turcotte-Pugh (CTP) score of 7 or 8, representing significant liver dysfunction. Six patients, or 22% of the study population, survived less than 12 weeks. The median sorafenib treatment duration was only nine weeks, a much shorter treatment duration than the referenced historical controls1. The median treatment duration of TTFields was 10 weeks.

“We are very encouraged by the HEPANOVA results, especially in light of the poor prognosis of the study population and low treatment exposure,” said Dr. Uri Weinberg, Novocure’s Chief Science Officer. “We intend to initiate a randomized controlled trial as soon as possible and are working with key opinion leaders to finalize a protocol incorporating the evolving treatment landscape in advanced liver cancer. We are particularly interested in the potential to use TTFields together with immunotherapy in this aggressive disease given in vivo data which suggest that using TTFields together with anti-PD-1 therapy results in increased tumor response versus either therapy alone.”

The objective response rate reached 9.5% in the 21 evaluable patients, more than double the historical controls. The disease control rate was 76%, a much higher rate than the historical controls of 43% to 52%. For the 11 patients who completed at least 12 weeks of TTFields therapy, the objective response rate was 18%. The disease control rate for patients who completed at least 12 weeks of TTFields therapy was 91%. The objective response rate is defined as the percentage of patients who achieved complete or partial response. The disease control rate includes the percentage of responders plus the patients who achieved stable disease. In the intent-to-treat population, median progression free survival was 5.8 months and median time-to-progression was 8.9 months, higher than the historical, sorafenib alone control for both endpoints. No increase in the toxicity of sorafenib and no device-related serious adverse events were reported.

https://www.businesswire.com/news/home/20210701005145/en/Novocure-Presents-Final-Safety-and-Efficacy-Results-from-its-Phase-2-Pilot-HEPANOVA-Trial-in-Liver-Cancer

CureVac to ‘plow forward’ with Covid vaccine despite disappointing results

 CureVac plans to continue work on its Covid-19 vaccine despite disappointing clinical trial results that showed the shot is just 48% effective.

The German biotech firm published its final analysis of the clinical trials of its coronavirus vaccine — known as CVnCoV — on Wednesday, confirming that the shot was 48% effective against Covid of any severity across all age groups and 15 variants.

Pierre Kemula, CFO of CureVac, defended the vaccine on CNBC Thursday, however, saying the clinical trials had been conducted at a time when multiple new strains of the virus were spreading across the world.

“We need now to speak to the EMA [European Medicines Agency] and want to make sure we have an open dialogue and share all the data we have to assess the path forward,” he told CNBC’s Squawk Box Europe Thursday.

When asked whether it was worth continuing to develop the vaccine when there are other successful shots already deployed in Europe and elsewhere, Kemula said the company had contractual obligations to fulfil.

“We have a contract with the European Commission to supply 225 million doses of the drug so I think, with that in mind, we need to plow forward,” he said.

“There’s plenty of jabs to be given, there’s plenty of people under the age of 60 that haven’t had access to the vaccine to date. So if we can contribute to fight — in the short-term in the pandemic, but also in the mid-term with these other avenues of [multivalents] ... that’s something we continue to work on.” Multivalent or polyvalent vaccines are designed to immunize against more than one strain of a virus.

The results of the CureVac trial, which involved 40,000 participants in ten countries in Latin America and Europe, showed the vaccine was more effective in younger participants. The efficacy rate among those aged 18 to 60 came in at 53% against disease of any severity, and rose to 77% against moderate and severe disease in the same age group.

However, as Covid-19 poses more risks for older people, the trial results are disappointing, not least because two other vaccines made using messenger RNA (mRNA) — those from Pfizer-BioNTech and Moderna — have proved to be over 90% effective at preventing Covid-19 infection.  Shares in CureVac dropped as much as 13% in pre-market trade Thursday.

CureVac CEO Dr Franz-Werner Haas also defended the results in a statement Wednesday, saying the vaccine “demonstrates a strong public health value” for those between 18 and 60 and will be an “important contribution to help manage the Covid-19 pandemic and the dynamic variant spread.”

He also cited “the current context of an increasingly diverse environment of Covid-19 variants.”

Multiple variants having emerged over the course of the pandemic, with some more virulent than others — such as the alpha variant first discovered in the U.K. and the delta variant first identified in India — and Kemula said he believed mutations would continue to occur.

“With more and more people infected with coronavirus, we are set for a continued evolution of the disease as it moves forward and has more and more variants,” Kemula said. The industry needed to think ahead on “how we can better manage this with current vaccines but also with different boosters (booster shots) potentially,” he added.

https://www.cnbc.com/2021/07/01/curevac-to-plow-forward-with-covid-vaccine-despite-trial-results-.html

Roche dismisses early filing chatter for its Alzheimer’s drug, remains focused on phase 3 trial

 An analyst report stating that Roche will seek early FDA approval for its Alzheimer’s disease candidate gantenerumab appears to have jumped the gun, according to comments from the Swiss pharma giant. 

Jefferies stated in a research note that Roche had met with FDA regulators last week and would be following in Eli Lilly's footsteps to file the candidate under an accelerated review pathway. 

But Roche told Fierce Biotech they would not "comment on speculations." Instead, the company is continuing with a phase 3 clinical trial for gantenerumab and more details will be shared when they are available. Discussions with the FDA and other regulatory authorities are being done "when appropriate." 

The news was the latest in a saga that began when the FDA approved Biogen's Aduhelm for Alzheimer's disease under the accelerated approval lane. The therapy is the first approved for the devastating neurological disease in decades and has set off a firestorm of speculation over which companies might leap through the door cracked open by Biogen. 

Aduhelm was approved by the FDA on the strength of data for a surrogate endpoint, thereby raising the possibility that developers of other Alzheimer’s candidates could get to market before completing big pivotal studies that show clinical benefit.

Lilly responded by committing to seek accelerated approval for donanemab later this year; however, Mizuho analysts said in a June 24 note that the company and the FDA "are not yet fully aligned" on the plan to submit the therapy. Donanemab was granted a breakthrough therapy tag, kicking off excitement that the drug may follow in Aduhelm's footsteps.   

Given the precedent Aduhelm set, Mizuho still thinks the FDA will accept and ultimately approve Lilly's drug. 

As for gantenerumab, Roche brought the drug candidate back from the dead in 2018, four years after it failed a phase 3 study, in the belief that a much higher dose may be more effective.

The 2014 flop, coupled with the later failure of a Washington University School of Medicine-sponsored study, leaves sizable doubts about whether gantenerumab can improve clinical outcomes. However, Roche has linked the new phase 3 dose to the removal of amyloid-beta plaque. In a post-Aduhelm world, data on amyloid-beta plaque removal could be enough to win accelerated approval.

Jefferies said that if gantenerumab is filed in the near future and granted priority review and a fast track designation, the drug could be headed for shelves under an accelerated approval late in the first quarter of 2022. This would be a year earlier than expected.

Roche is expecting data from the late stage trial to arrive in the second half of next year, putting the Jefferies timeline firmly out of reach if the Swiss pharma intends to wait. 

If gantenerumab comes to market, it could have advantages over the potential pool of rivals such as Biogen’s Aduhelm. Notably, gantenerumab is administered subcutaneously over five minutes, making it quicker and easier to deliver than intravenous therapies such as Aduhelm. The Jefferies analysts forecast gantenerumab sales of $3 billion but assign a 0% probability of success to the candidate. 

https://www.fiercebiotech.com/biotech/roche-to-seek-early-fda-approval-for-alzheimer-s-drug-following-lilly-through-door-blown

Arcutis ends trial of vitiligo treatment candidate, to reformulate

 

• Formulation-related observations from ARQ-252 trial in chronic hand eczema informed early termination of Phase 2a ARQ-252 trial in vitiligo
  

• Company progressing new formulation with goal of greater drug delivery to targets in the skin

https://finance.yahoo.com/news/arcutis-provides-phase-2a-clinical-100000416.html

Immunic gets FDA OK to start Phase 2, 3 MS studies

 Phase 3 ENSURE Program in Relapsing-Remitting Multiple Sclerosis (RRMS) Comprises Twin Studies Evaluating Efficacy, Safety, and Tolerability of IMU-838 Versus Placebo, Intended to Provide Straightforward Path to Regulatory Approval -

- Supportive Phase 2 CALLIPER Trial in Progressive Multiple Sclerosis (PMS), Designed to Corroborate IMU-838's Neuroprotective Potential and Support Differentiated Profile -

- Company Expects Initiation of Both ENSURE and CALLIPER in the Second Half of 2021 -

- Conference Call and Webcast to be Held July 1, 2021 at 8:00 am ET -

Conference Call and Webcast Information

Immunic's management team will host a public conference call and webcast on July 1, 2021 at 8:00 a.m. Eastern Time to discuss the company's overall MS development strategy, the phase 3 ENSURE program in RRMS, and the phase 2 CALLIPER trial in PMS.

To participate in the conference call, dial 1-877-870-4263 (USA) or 1-412-317-0790 (International) and ask to be joined into the Immunic, Inc. call. A live, listen-only webcast of the conference call can be accessed at https://www.webcaster4.com/Webcast/Page/2301/39951 or on the "Events and Presentations" section of Immunic's website at ir.imux.com/events-and-presentations.

https://finance.yahoo.com/news/immunic-inc-announces-fda-clearance-103000225.html

Safety and Efficacy of NVX-CoV2373 Covid-19 Vaccine

 

Paul T. Heath, F.R.C.P.C.H., 

Eva P. Galiza, M.B., B.S., 

David N. Baxter, M.D., Ph.D., 

Marta Boffito, M.D., Ph.D., 

Duncan Browne, M.D., 

Fiona Burns, Ph.D., 

David R. Chadwick, Ph.D., 

Rebecca Clark, M.B., Ch.B., 

Catherine Cosgrove, Ph.D., 

James Galloway, Ph.D., 

Anna L. Goodman, D.Phil., 

Amardeep Heer, M.B., Ch.B., 

 for the 2019nCoV-302 Study Group*

DOI: 10.1056/NEJMoa2107659

PDF: 

https://www.nejm.org/doi/pdf/10.1056/NEJMoa2107659?articleTools=true

Abstract

BACKGROUND

Early clinical data from studies of the NVX-CoV2373 vaccine (Novavax), a recombinant nanoparticle vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that contains the full-length spike glycoprotein of the prototype strain plus Matrix-M adjuvant, showed that the vaccine was safe and associated with a robust immune response in healthy adult participants. Additional data were needed regarding the efficacy, immunogenicity, and safety of this vaccine in a larger population.

METHODS

In this phase 3, randomized, observer-blinded, placebo-controlled trial conducted at 33 sites in the United Kingdom, we assigned adults between the ages of 18 and 84 years in a 1:1 ratio to receive two intramuscular 5-μg doses of NVX-CoV2373 or placebo administered 21 days apart. The primary efficacy end point was virologically confirmed mild, moderate, or severe SARS-CoV-2 infection with an onset at least 7 days after the second injection in participants who were serologically negative at baseline.

RESULTS

A total of 15,187 participants underwent randomization, and 14,039 were included in the per-protocol efficacy population. Of the participants, 27.9% were 65 years of age or older, and 44.6% had coexisting illnesses. Infections were reported in 10 participants in the vaccine group and in 96 in the placebo group, with a symptom onset of at least 7 days after the second injection, for a vaccine efficacy of 89.7% (95% confidence interval [CI], 80.2 to 94.6). No hospitalizations or deaths were reported among the 10 cases in the vaccine group. Five cases of severe infection were reported, all of which were in the placebo group. A post hoc analysis showed an efficacy of 86.3% (95% CI, 71.3 to 93.5) against the B.1.1.7 (or alpha) variant and 96.4% (95% CI, 73.8 to 99.5) against non-B.1.1.7 variants. Reactogenicity was generally mild and transient. The incidence of serious adverse events was low and similar in the two groups.

CONCLUSIONS

A two-dose regimen of the NVX-CoV2373 vaccine administered to adult participants conferred 89.7% protection against SARS-CoV-2 infection and showed high efficacy against the B.1.1.7 variant. (Funded by Novavax; EudraCT number, 2020-004123-16. opens in new tab.)

https://www.nejm.org/doi/full/10.1056/NEJMoa2107659

Regeneron, GlaxoSmithKline and Eli Lilly COVID-19 drugs prioritized for expedited review in Europe

 Amid the global war on pandemic variants, the European Union has identified five COVID-19 therapeutics it will prioritize with the hope to authorize three by October.

Europe has selected four monoclonal antibody regimens—Eli Lilly's bamlanivimab/etesevimab combo, Celltrion’s regdanvimab, Regeneron and Roche’s casirivimab/ imdevimab cocktail and GlaxoSmithKline and Vir Biotechnology’s sotrovimab.

Also on the list is Eli Lilly’s baricitinib, a treatment already approved as Olumiant to treat rheumatoid arthritis and atopic dermatitis. The drug reduces the activity of the immune system and has been repurposed for COVID-19 patients on oxygen.

The effort is aimed at providing more regulatory flexibility with rolling reviews, conditional marketing authorizations and flexible labelling and packaging requirements. It also will allow for more scientific support from the European Medicines Agency and for the bloc to facilitate partnerships within the industry.

To that end, the EU will hold an industry "matchmaking event” on July 12 and 13. Officials aim to identify and address supply chain bottlenecks and make plans to immediately boost production for the drugs upon their potential approvals.

An apparent frontrunner is the antibody treatment from Regeneron. In February, the EMA issued a positive opinion on the cocktail for patients at risk of progressing to severe COVID-19. Earlier this month, the EU purchased 55,000 doses of the drug.

Lilly’s bamlanivimab and etesevimab combo was the first to win approval in the United States for COVID-19 patients at risk for progressing to a severe form of the disease. But with the cocktail showing weakness against COVID variants from Brazil and South Africa, the U.S. halted its use last week.

The sotrovimab antibody from GSK/Vir scored authorization for use in America last month, but the companies have yet to cut a deal with the U.S. to supply it.

Last October, Europe purchased 500,000 doses of Gilead's remdesivir for $1.2 billion. But a month later, the bloc suspended its use after the World Health Organization declared the drug ineffective for patients hospitalized with COViD-19.

The EU hopes to add more promising treatments to the portfolio, targeting 10 by the end of the year “subject to R&D outcomes,” it explained in a release.

https://www.fiercepharma.com/pharma/covid-19-treatments-from-regeneron-lilly-gsk-vir-among-5-prioritized-for-expedited-review