17 MARCH 2020

Imfinzi’s success in ES-SCLC not matched in combo with tremelimumab

AstraZeneca’s Imfinzi (durvalumab) plus standard of care (SoC) chemotherapies caused a sustained, clinically meaningful overall survival (OS) benefit in first line treatment of extensive-stage small cell lung cancer (ES-SCLC), according to a final analysis of the Phase III CASPIAN trial.

However, a second arm in the CASPIAN study where Imfinzi and SoC was combined with tremelimumab did not meet its primary endpoint of statistically significant improvement in OS, compared to chemotherapy alone.

Imfinzi is an anti-programmed cell death-ligand 1 (PD-L1) monoclonal antibody, while tremelimumab is an anti-cytotoxic T-lymphocyte–associated antigen 4 (CTLA4) monoclonal antibody. AstraZeneca is trialling these two antibodies in combination in a range of cancers, including non-SCLC, bladder cancer, and head and neck cancer.

The safety data of Imfinzi plus SoC and tremelimumab was consistent with the known profiles of these medicines.

AstraZeneca is currently awaiting approval for Imfinzi plus SoC chemotherapies etoposide and either carboplatin or cisplatin in the first line setting for ES-SCLC in the US, the European Union and Japan. The company recently received approval in this treatment group in Singapore. The drug was also granted priority review by the US Food and Drug Administration in December last year.

These approvals are based upon the final OS results announced today, as well as interim analysis published in June 2019.

AstraZeneca Oncology R&D executive vice-president José Baselga said: “We are pleased to see the sustained and meaningful survival benefit of Imfinzi for patients with small cell lung cancer after more than two years median follow up.

“We have already received the first global regulatory approval for Imfinzi with etoposide plus either carboplatin or cisplatin and remain on track for more approvals soon as we provide patients an important new 1st-line treatment option.”

Imfinzi is also being studied following concurrent chemoradiation in patients with limited-stage SCLC; results of the Phase III ADRIATIC study are expected in 2021.

17 MARCH 2020

 J&J says no evidence darunavir works against coronavirus

Johnson and Johnson (J&J) have noted the lack of evidence that its HIV drug darunavir has antiviral activity against SARS-CoV-2, the novel coronavirus that causes Covid-19.

Currently, HIV protease inhibitors are being considered as potential treatments for the new viral infection. J&J says that the use supports limited, unpublished virologic and clinical data in SARS coronavirus patients.

Darunavir is a protease inhibitor marketed by the company’s unit Janssen Pharmaceutical. The drug has approval as a boosting agent for use in combination with other antiretrovirals to treat HIV-1.

Janssen does not have any clinical nor pharmacological evidence allow the inclusion of darunavir / cobicistat in Covid-19 treatment guidelines.

Furthermore, there are no published safety and efficacy data of darunavir / cobicistat in Covid-19 patients.

To date, no in-vitro studies or clinical trials took place to assess the safety and efficacy of darunavir / cobicistat or darunavir / cobicistat / emtricitabine / tenofovir alafenamide for coronavirus treatment.

In a statement, J&J said: “Johnson & Johnson has no evidence that darunavir has any effect against SARS-CoV-2, the virus that causes Covid-19.

“Johnson & Johnson is screening its antiviral compounds, including darunavir, to determine potential in vitro effect against SARS-CoV-2. We are partnering with multiple organisations to support the development of research programmes and fast-track solutions for Covid-19.”

Janssen provided darunavir-based medicines for three clinical studies in China.

17 MARCH 2020

First US clinical trial of Covid-19 vaccine candidate begins

The first US clinical trial of a Covid-19 vaccine candidate, which is Moderna’s mRNA-1273, has started at Kaiser Permanente Washington Health Research Institute (KPWHRI) in Seattle.

Funded by the National Institutes of Health (NIH)’s National Institute of Allergy and Infectious Diseases (NIAID), the trial has dosed its first participant.

mRNA-1273 is an mRNA vaccine designed to target SARS-CoV-2 encoding a prefusion stabilised form of the Spike (S) protein. Moderna selected the candidate in alliance with the Vaccine Research Center (VRC) at the NIAID.

The Coalition for Epidemic Preparedness Innovations (CEPI) funding supported the production of the first clinical batch.

During the Phase I trial, the safety and immunogenicity of 25μg, 100μg, 250μg dose levels of mRNA-1273 given on a two-dose vaccination schedule 28 days apart will be assessed in a total of 45 healthy adults aged 18 to 55.

The study involves a follow-up of 12 months after the second vaccination.

The primary objective is the safety and reactogenicity of a two-dose vaccination schedule, while the secondary objective is immunogenicity to the SARS-CoV-2 S protein.

Moderna chief medical officer Tal Zaks said: “This study is the first step in the clinical development of an mRNA vaccine against SARS-CoV-2, and we expect it to provide important information about safety and immunogenicity. We are actively preparing for a potential Phase II study under our own IND.

“We are grateful to NIH for their ongoing collaboration and to CEPI for funding the initial manufacturing of mRNA-1273 and are proud to be included with the many companies, worldwide health agencies and NGOs working on a possible response to the novel coronavirus outbreak.”

The potential Phase II and any subsequent trials will further evaluate the safety and immunogenicity of the vaccine candidate in a larger population. Moderna has already started manufacturing the mRNA-1273 material for the Phase II study.

17 MARCH 2020

Eli Lilly receives breakthrough status for baricitinib in alopecia

Eli Lilly and its partner Incyte have received breakthrough therapy designation from the US Food and Drug Administration (FDA) for baricitinib to treat alopecia areata.

Alopecia areata is an autoimmune skin condition characterised by the irregular hair loss on the scalp, face and other body parts. The disease usually develops during childhood and can be unique for everyone.

Marketed as Olumiant, baricitinib is an oral Janus kinase (JAK) inhibitor.

The drug already holds approval to treat moderately to severely active rheumatoid arthritis in adults who do not experience an adequate response to one or more TNF inhibitor therapies.

Eli Lilly immunology development vice-president Lotus Mallbris said: “Patients with alopecia areata currently do not have any FDA-approved treatment options available to them. Alopecia areata not only causes hair loss but also may be a psychosocial burden for people living with this disease.

“At Lilly, we aspire to create new medicines that can give hope to patients. We look forward to working with the FDA to further explore baricitinib’s potential to become the first approved treatment option for these individuals.”

The latest FDA decision supports Phase II findings in the adaptive Phase II / II BRAVE-AA1 clinical trial. The study compared baricitinib to placebo in adult patients.

In the Phase II part of the trial, no new safety signals or serious adverse events were identified up to week 36.

Furthermore, the treatment-emergent adverse events (TEAEs) were mild or moderate, with the most common events being upper respiratory tract infections, nasopharyngitis and acne.

Based on the interim data of the Phase II part, BRAVE-AA1’s Phase III portion and a separate Phase III BRAVE-AA2 trial are investigating the safety and efficacy of 2mg and 4mg baricitinib.

Earlier this month, Lilly partnered with AbCellera Biologics to co-develop antibodies to treat and prevent Covid-19 coronavirus infection.

16 MARCH 2020

Pfizer to develop potential Covid-19 vaccine and drugs

Pfizer has confirmed that the company has initiated efforts to advance its potential antiviral therapies and also develop a vaccine against Covid-19.

The company is in discussions with its existing partner BioNTech to create a potential mRNA coronavirus vaccine.

Earlier this month, Pfizer identified several antiviral compounds, already in development, with potential to block coronaviruses.

Pfizer chairman and CEO Dr Albert Bourla said: “Many companies, including Pfizer, are working to develop antiviral therapies to help infected patients fight this emerging virus as well as new vaccines to prevent infection and halt the further spread of this disease.

“Pfizer is working to advance our own potential antiviral therapies and is engaged with BioNTech on a potential mRNA coronavirus vaccine. We are committed to working as one team across the industry to harness our scientific expertise, technical skills and manufacturing capabilities to combat this evolving crisis.”

The company is adopting a five-point strategy to fight the ongoing Covid-19 pandemic globally.

Companies and researchers are developing cell-based assays, screening, serological assays and translational models to assess potential therapies and vaccines for coronavirus.

The tools developed by Pfizer will be available on an open-source platform. The company will also share its data and insights with other companies in real-time.

Pfizer has a dedicated team of virologists, biologists, chemists, clinicians, epidemiologists, vaccine experts and pharmaceutical scientists, among other experts, to work only on combating the outbreak.

The team is working to rapidly discover and develop therapies and vaccines.

Pfizer will also share its clinical development and regulatory expertise with smaller biotech firms in order to support the most promising candidates against Covid-19.

The company will also provide its manufacturing capabilities to rapidly scale and deploy an approved coronavirus therapy or vaccine.

13 MARCH 2020

Pluristem forms Covid-19 drug development alliance

Israel-based Pluristem Therapeutics has collaborated with the BIH Center for Regenerative Therapy (BCRT) and the Berlin Center for Advanced Therapies (BeCAT) at Charite’ University of Medicine Berlin to work on Covid-19 therapies.

The partnership will see a joint project to explore Pluristem’s PLX cell product candidates for treating respiratory and inflammatory complications caused by the novel coronavirus infection.

PLX cells trigger the immune system’s regulatory T-cells and M2 macrophages, expected to help reduce fatal pneumonia and pneumonitis symptoms induced by Covid-19.

In prior preclinical studies, PLX cells showed significant therapeutic effects against pulmonary hypertension, lung fibrosis, acute kidney injury and gastrointestinal injury in animal models.

These health conditions are considered potential complications of severe Covid-19 infection.

Pluristem Therapeutics president and CEO Yaky Yanay said: “The collaboration with Charité researchers will allow us to expedite our program to potentially enable the use of PLX cells to treat patients infected with COVID-19 that have respiratory and immunological complications.

“The fact that PLX is available off-the-shelf, combined with our ability to manufacture large scale quantities, is a key advantage in case a large number of patients may need respiratory support.

“The primary target is to prevent the deterioration of patients towards Acute Respiratory Distress Syndrome (ARDS) and sepsis.”

13 MARCH 2020

ImmunoPrecise uses PolyTope mAb Therapy for Covid-19

ImmunoPrecise Antibodies is set to use PolyTope mAb Therapy approach for the development of a universal COVID-19 therapy.

The approach builds on the company’s discovery platforms and artificial intelligence (AI) capabilities with its partner, EVQLV.

According to the company, the proposed curative treatments such as polyclonal, sensitised serum or individual monoclonal antibodies may not be effective after viral mutation.

ImmunoPrecise’s approach involves various mechanisms of the immune system, predicts mutations within the virus genome, along with additional characteristics for a maximum clinical benefit against existing and future strains.

ImmunoPrecise Antibodies coronavirus global project leader Ilse Roodink said: “Our PolyTope mAb Therapy perfectly combines the benefits of using well-defined and fully characterised monoclonal antibodies with the essential need for a multi-targeting strategy to tackle this quickly emerging virus, thereby significantly accelerating effective clinical application”.

In February this year, ImmunoPrecise initiated a research programme focused on the development of vaccine and therapeutic antibodies against SARS-CoV-2.

13 MARCH 2020

FDA fast-tracks empagliflozin in chronic kidney disease

Boehringer Ingelheim and Eli Lilly have received the US Food and Drug Administration (FDA) fast track designation for the evaluation of empagliflozin to treat chronic kidney disease in adults.

The drug mitigates the risk of kidney disease progression and cardiovascular death.

Marketed as Jardiance, empagliflozin is an oral, once-daily inhibitor of sodium-glucose cotransporter 2.

It is the first drug approved to decrease the risk of cardiovascular death in adults suffering from type 2 diabetes and established cardiovascular disease.

Eli Lilly product development vice-president Jeff Emmick said: “We recognise the close link between the health of the heart, kidneys and metabolic system, and we have committed to a broad clinical development programme assessing the cardiorenal metabolic benefits of empagliflozin.

“The fast track designation from the FDA is an important step in evaluating the potential of empagliflozin to enhance care for those with chronic kidney disease.”

Currently, empagliflozin is being studied in the ongoing EMPA-KIDNEY clinical study in adults having chronic kidney disease with and without diabetes.

The aim is to assess the drug’s effect on the progression of kidney disease and cardiovascular death. EMPA-KIDNEY comes from exploratory data of EMPA-REG OUTCOME clinical trial.

In the EMPA-REG OUTCOME trial, empagliflozin led to a 39% decrease in the risk of new-onset and worsening kidney disease in adults with type 2 diabetes and cardiovascular disease, compared to placebo.

The University of Oxford’s Medical Research Council Population Health Research Unit is performing and reporting EMPA-KIDNEY independently. Boehringer and Lilly are funding the study.

Last July, the FDA awarded fast track status for empagliflozin to decrease the risk of cardiovascular death and hospitalisation for heart failure in chronic heart failure patients.

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