Arbutus, Vaccitech Collaborate on RNAi Therapeutic-Immunotherapeutic for Chronic Hepatitis B

 Arbutus Biopharma Corporation (Nasdaq: ABUS) and Vaccitech plc (Nasdaq: VACC) today announced that the companies have entered into a clinical trial collaboration agreement to evaluate an innovative therapeutic combination for the treatment of subjects with chronic hepatitis B virus (HBV) infection (CHB) who are already receiving standard-of-care nucleos(t)ide reverse transcriptase inhibitor (NrtI) therapy.

The multi-center, Phase 2a clinical trial will evaluate the safety, pharmacokinetics, immunogenicity, and antiviral activity of Arbutus’s proprietary GalNAc delivered RNAi therapeutic, AB-729, followed by Vaccitech’s proprietary immunotherapeutic, VTP-300, in NrtI-suppressed subjects with CHB. The Phase 2a clinical trial is expected to initiate in the second half of this year and will be managed by Arbutus, subject to oversight by a joint development committee comprised of representatives from Arbutus and Vaccitech. The parties retain full rights to their respective product candidates and will split all costs associated with the clinical trial. Pursuant to the agreement, the parties intend to undertake a larger Phase 2b clinical trial depending on the results of the initial Phase 2a clinical trial.

“Based on the positive clinical results we have seen in our ongoing Phase 1a/1b clinical trial for AB-729, including recent data demonstrating increased HBV-specific immune responses, we believe AB-729 has the potential to become a cornerstone therapeutic in multiple future HBV combination regimens,” stated Gaston Picchio, Chief Development Officer at Arbutus. “We are looking forward to initiating this proof-of-concept Phase 2a clinical trial, which will allow us to evaluate the combination of two promising clinical candidates with potential complimentary mechanisms of action. We believe combining AB-729, which is designed to reduce HBsAg resulting in increased HBV immune responses with VTP-300, an immunotherapeutic designed to elicit an HBV specific immune response, may offer patients with CHB a much needed and durable functional cure.”

https://finance.yahoo.com/news/arbutus-biopharma-vaccitech-announce-clinical-110000423.html

Athira Pharma Starts Label Extension Study for Trials of ATH-1017 for Alzheimer’s

 Athira Pharma, Inc. (NASDAQ: ATHA), a late clinical-stage biopharmaceutical company focused on developing small molecules to restore neuronal health and stop neurodegeneration, today announced that it is enrolling patients into an open label extension (OLEX) study for its ongoing Phase 2/3 LIFT-AD and Phase 2 ACT-AD studies of ATH-1017 for the treatment of mild-to-moderate Alzheimer’s disease.

“This treatment extension allows us to meet investigator and patient interest in continuing treatment with ATH-1017. We can now collect up to 1 year of safety and efficacy data on ATH-1017, and patients who received placebo during the randomized portion of the trial will now be able to receive up to 26 weeks of therapy,” said Hans Moebius, M.D., Ph.D., Chief Medical Officer at Athira. “It’s rewarding to have our first patients completing six months of study now continue their treatment. Our novel treatment approach is agnostic to the underlying disease pathology and is designed to focus on neuronal regeneration, which has the potential to improve clinical outcomes for patients.”

“There remains an urgent need for therapies that improve cognition for patients who are living with mild-to-moderate Alzheimer’s disease,” said Michael Mega, M.D., Ph.D., Director of the Center for Cognitive Health and a principal investigator in the ACT-AD trial. “The data we will continue to collect in this open label extension could help us to better understand the long-term safety and efficacy profile of ATH-1017 and could help Athira best design future clinical trials of ATH-1017.”

The LIFT-AD and ACT-AD trials are evaluating ATH-1017, a small molecule therapeutic designed to enhance the activity of Hepatocyte Growth Factor (HGF) and its receptor, MET, which are expressed in the central nervous system, in order to promote brain health and function. The randomized, double-blind, placebo-controlled trials are evaluating the safety and efficacy of ATH-1017 in mild-to-moderate Alzheimer’s disease. Patients are stratified 1:1:1 to receive low dose ATH-1017 (40 mg/day), high dose ATH-1017 (70 mg/day) or placebo.

https://finance.yahoo.com/news/athira-pharma-announces-initiation-open-110000891.html

Provention Bio slapped with FDA rejection for diabetes hopeful teplizumab

 After scraping through a tough advisory committee in March, the FDA has returned a verdict for Provention Bio’s Type 1 diabetes medicine: It’s a no.

Specifically, the FDA has slapped a complete response letter on Provention for teplizumab, which was gunning for an approval to help delay clinical Type 1 diabetes in at-risk individuals.

In the trial that underpinned the drug’s application, Provention said teplizumab delayed the onset of Type 1 diabetes by a median of two years. That delay could help patients avoid diabetic ketoacidosis, a life-threatening complication of diabetes.

Back in March, FDA experts assessing the drug raised concerns about how small the study was—it didn’t meet its enrollment goal and wound up testing teplizumab in just 44 patients—and about the fact that the study did not follow patients after their diabetes diagnosis.

The company also submitted safety data from other trials of the drug in another indication, which the FDA reviewers noted were not a perfect comparison.

Now, the FDA is sharing its own concers, many of which were predicted. In a release from the biotech (the FDA doesn’t publicize complete response letters itself), the FDA stated that a single, low-dose pharmacokinetic/pharmacodynamic (PK/PD) bridging study in healthy volunteers to compare planned commercial product with drug product originating from drug substance manufactured for historic clinical trials “had failed to show PK comparability.”

“As PK remains the primary endpoint for demonstration of comparability between the two products, you will need to establish PK comparability appropriately between the intended commercial product and the clinical trial product or provide other data that adequately justify why PK comparability is not necessary,” the FDA said, as quoted by Provention.

The FDA is also asking for a “safety update” as part of its BLA resubmission, though Provention gave no specifics here.

The biotech said it expects “relevant additional” PK/PD data out from a PK/PD sub-study in patients receiving 12 days of therapy in the ongoing phase 3 Protect trial in newly diagnosed Type 1 diabetes patients “later this quarter.”

These data “will determine whether to submit these data to the FDA for its review,” Provention said, “to support PK comparability or otherwise justify why PK comparability is not necessary.”

And it doesn’t end there: There were also some manufacturing issues. The FDA uncovered “certain deficiencies” amid a recent general inspection at a fill/finish manufacturing facility, and, though not specific to teplizumab, this will need “to be resolved before approval.”

“The CRL contained other comments and recommendations that do not impact approvability, as well as general guidance regarding the resubmission process,” but again gave no details about these.

We do know that this will cause delay and likely more expense, and further knocks back the biotech, which had been flying high ahead of its advisory committee though was brought back to Earth by its squeezing past.

The company had been bullish that it could bypass some of these issues, but clearly, the FDA had other ideas.

“We want to recognize the patients, their families, study investigators, clinicians and T1D champions that have played such a crucial role in the development of teplizumab and thank our partners and our team of dedicated employees and consultants for their outstanding contributions,” said Ashleigh Palmer, co-founder and CEO of Provention Bio.

“We also want to acknowledge the efforts of Drs. Yanoff and Unger and the review team at the FDA, who have worked so closely and transparently with us throughout the priority review of our BLA for this Breakthrough Therapy drug.

“We know the T1D community is urgently awaiting therapeutic advancements to address their medical needs and believe our collective passion and commitment will continue to drive us forward to meet this goal. We will continue to work collaboratively with the FDA to hopefully secure approval of teplizumab and bring the first disease-modifying therapy for T1D to at-risk patients as soon as possible.”

https://www.fiercebiotech.com/biotech/provention-bio-slapped-fda-rejection-for-diabetes-hopeful-teplizumab

Innate Pharma Stops Exploration of Avdoralimab in Treatment for Covid-19

 Innate Pharma SA said Tuesday that it would no longer explore its drug avdoralimab in Covid-19 after missing its Phase 2 targets but would continue to investigate its use in inflammation.

The oncology-​focused biotech company said it didn't meet its primary endpoints in all three of its trial cohorts of Covid-19 patients with severe pneumonia.

The company said preclinical data that were observed didn't translate into clinical benefit over best supportive care.

Innate Pharma said these results don't affect the investigator-sponsored, Phase 2 trial of the treatment in the inflammatory disease bullous pemphigoid, for which it is enrolling patients.

https://www.marketwatch.com/story/innate-pharma-stops-exploration-of-avdoralimab-in-treatment-for-covid-19-271625566941

Chinese Pharma Stocks Drop on Proposed New Rules for Oncology Drug Trials

 Chinese pharmaceutical shares skidded Tuesday as new draft rules for conducting oncology drug trials could increase research and development costs, analysts said.

Shanghai Fosun Pharmaceutical (Group) Co.'s A-shares shed 9.6%, while Hangzhou Tigermed Consulting Co. fell 11% and WuXi AppTec Co. declined 5.1%. The companies' Hong Kong-listed shares lost between 4.7%-8.6%.

A draft of the policy, released Friday by China's Center for Drug Evaluation, takes aim at "the low quality and repetitive R&D" of drugs developed in China, and seeks to push pharmaceutical companies to focus on innovation, said Daiwa Capital Markets analyst Dennis Ip.

Tigermed, which provides clinical research services for pharmaceutical product development, might be hit relatively hard in the short term, given its heavy reliance on Chinese clients for revenue, Mr. Ip said. Other companies like WuXi AppTec and Wuxi Biologics (Cayman) Inc. will be less affected since their largest revenue sources are from international clients, he added.

Changes in regulation will likely have limited impact on drugs that are already in the clinical-trial stage, given that the draft rules are still in the consultation stage, Soochow Securities said. The brokerage said higher requirements for conducting clinical trials should benefit drugmakers with greater capital resources and experience in clinical-trial designs.

https://www.marketscreener.com/quote/stock/SHANGHAI-FOSUN-PHARMACEUT-6548924/news/Chinese-Pharma-Stocks-Drop-on-Proposed-New-Rules-for-Oncology-Drug-Trials-35795850/

A battery-free pacemaker that can be absorbed by the body

 

ADOBE

Scientists have designed a temporary, battery-free pacemaker that can be broken down by the patient’s body when its work is done, the latest advance in the emerging field of bioelectronics.

In a paper published this week in Nature Biotechnology, researchers report that the device reliably kept the heart’s pace in check in tests on mice, rats, and other animals, as well as in human heart tissue in a dish. And while the research is still in the early stages, the scientists say the pacemaker was able to overcome key limitations of existing devices.

“There are about 1 million people a year who receive pacemaker implantations worldwide. It’s a huge, huge medical field, but mostly pacemakers are permanent,” said Igor Efimov, a biomedical engineer and professor at George Washington University and co-author of the new paper.

Unlike traditional pacemakers, which are left inside a patient for the rest of their life or until the battery dies, a traditional temporary pacemaker is implanted and later removed. The devices are typically for children with congenital heart defects or adults who have had a coronary artery bypass graft, who may need a temporary pacemaker to correct a slowed heart rhythm for only a few days or weeks.

A traditional temporary pacemaker has wires connected to the heart, which poke out of the skin and attach to external hardware. Some experts say that setup could raise the risk of infection, potentially injure the heart when the lead is removed, and can hamper patient mobility. Being able to move around after surgery is especially valuable as patients recover.

“The patient will be more free to move around after the surgery,” said Moussa Mansour, director of the Atrial Fibrillation Program at Massachusetts General Hospital. Mansour, who was not involved in the research, added that “the more you keep the patient in bed, the more likely they are to develop clots in their legs or pneumonia” or other complications.

The new device overcomes some of those challenges with the help of an external coil that can be sewn into a patient’s shirt or placed as a patch on the patient’s chest, where it transmits energy to power the pacemaker.

“You know when you try to charge a phone wirelessly? It’s exactly the same principle,”  said Efimov.

Because all of the complex programming for the pacemaker is done not in the device itself, but in external hardware, it isn’t confined by circuits that would otherwise be needed to communicate and process heart information. That means the device can be tiny and thin — less than a millimeter thick — which makes it easier to implant.

“It’s restricted just by the size of the antenna, which will harness the energy,” said Efimov.

Efimov and his colleagues were able to build on past research into bioresorbable materials, which have been developed and used for other applications for years. They selected materials that could be slowly and safely absorbed by the body. The thickness or type of materials used can change depending on how long the temporary pacemaker needs to last. The materials — some organic, silicone-based, or metals like magnesium — are also relatively affordable and comparable to the costs of a typical pacemaker, according to Efimov. The primary cost for manufacturing the devices would come from the external hardware the device requires.

Mansour said that while such a device would not necessarily increase the life span of a patient beyond what current pacemakers accomplish, it could improve patient quality of life.

“It seems to be a very revolutionary idea. I believe it’s going to be well-received in the field. It targets an unmet need, and I believe it’s going to benefit patients,” said Mansour.

The device could be beneficial for hospitals, Mansour said, given that patients who require a temporary pacemaker are typically roomed in the intensive care unit — valuable real estate in a hospital setting. Because patients with this new device wouldn’t be fixed to a single spot, the ICU could be reserved for patients who need the space more.

He also sees value in the research beyond its initial target. A biodegradable platform could be useful in treating a number of other conditions.

“That’s where the strength of this technology is,” Mansour said, “not only because it targets a temporary patient application, but because of its potential to be expanded to other applications in medicine.”

https://www.statnews.com/2021/07/02/temporary-pacemaker-heart-disease/

Japan to ship millions more COVID-19 vaccines to Taiwan, Asian neighbours this week

 Japan said on Tuesday it would ship millions more doses of AstraZeneca Plc's COVID-19 vaccine to Asian neighbours this week as a continuation of bilateral donations.

Japan will send 1.13 million more doses to Taiwan on Thursday, Foreign Minister Toshimitsu Motegi told reporters at a regular press conference, after previously delivering 1.24 million doses last month.

A further 1 million doses each will be sent to Thailand, the Philippines, and Vietnam this week, following earlier donations to Indonesia and Malaysia, Motegi said.

"True friends always lend a hand when they need each other the most," Taiwanese Premier Su Tseng-chang wrote on his Facebook page.

In further good news for Taiwan's vaccine programme, Health Minister Chen Shih-chung told reporters in Taipei that 620,000 additional AstraZeneca doses would arrive on Wednesday, part of the government's direct order from the company.

Japan has arranged to buy 120 million doses of AstraZeneca's vaccine, with most of that supply produced by domestic companies. Regulators approved the shot in May, but amid lingering concerns about blood clots, health authorities have relied on the mRNA-type vaccines made by Pfizer Inc and Moderna Inc in Japan's inoculation push.

Japan has pledged $1 billion and 30 million doses to the global vaccine sharing scheme COVAX, but so far its donations have been outside of that programme.

AstraZeneca doses produced in Japan have not yet been approved by the World Health Organisation for use in COVAX, Motegi said, so the country has turned to bilateral deals to respond to "urgent requests for vaccine supplies."

Japan's first shipments through the COVAX facility are expected in the middle of this month, with some 11 million doses bound for nations in south Asia and the Pacific islands, Motegi said. 

https://news.trust.org/item/20210706035316-u1bl0