18 FEBRUARY 2020

China approves first anti-viral drug against coronavirus Covid-19

Anti-viral drug Favilavir has secured approval from the National Medical Products Administration of China to treat coronavirus Covid-19, according to media reports.

China Daily reported that the Taizhou government in Zhejiang province announced the approval, which marks the authorisation of the first drug against the new coronavirus.

Formerly Fapilavir, the drug was developed by Zhejiang Hisun Pharmaceutical.

Fapilavir allegedly demonstrated efficacy with minor side effects in an ongoing 70-patient clinical trial in Shenzhen, Guangdong province. The drug’s generic version received the approval.

Production of the anti-viral drug was begun on Sunday, added the news agency.

According to China’s Ministry of Science and Technology, Favilavir is one of the three drugs that showed encouraging profile for blocking the new coronavirus in early clinical trials.

The remaining two drugs are anti-malaria drug chloroquine and Gilead’s experimental drug remdesivir.

Chloroquine, an existing medicine, is under assessment in more than 100 patients at over ten hospitals in Beijing and Guangdong province. Plans for an additional study in Hunan province are underway.

Meanwhile, Gilead is said to be in studies at more than ten medical institutions in Wuhan, the epicentre of the Covid-19 outbreak.

A study by the US National Institutes of Health (NIH) revealed that remdesivir could prevent the Middle East respiratory syndrome coronavirus (MERS-CoV), a type of coronavirus in monkeys, offering hope for China trials.

Earlier this month, the Wuhan Institute of Virology filed an application seeking a new patent on remdesivir.

18 FEBRUARY 2020

WHO says new coronavirus not as deadly as others

World Health Organization (WHO) director-general Dr Tedros Adhanom Ghebreyesus has said the new coronavirus Covid-19 is not as deadly as other coronaviruses, such as SARS and MERS.

These remarks come from a study paper released by the Chinese Centre for Disease Control and Prevention (CCDC) on 17 February.

The study includes data from more than 44,000 confirmed Covid-19 cases as of 11 February, making it the most comprehensive investigation since the coronavirus outbreak started in December.

WHO notes that the data provides better insights into the age range of patients, severity of the disease, as well as mortality rate.

Ghebreyesus added that the data indicates a decline in new cases. However, the situation is too early to determine if the decline will continue.

Commenting on the decline, Ghebreyesus said: “This trend must be interpreted very cautiously. Trends can change as new populations are affected. It’s too early to tell if this reported decline will continue. Every scenario is still on the table.”

According to the study, more than 80% of infected people have mild disease, which approximately 14% are severe and around 5% are critical.

Severe cases include pneumonia and shortness of breath, and critical crises include respiratory failure, septic shock and multi-organ failure.

The mortality rate among the infected remains as low as 2%, but the risk of death is more in people aged above 80 years. Also, men are at more risk compared to women.

Furthermore, the study finds that existing illnesses such as cardiovascular disease, diabetes, chronic respiratory disease and hypertension increase the risk of death.

The paper also revealed that a total of 1,716 health workers have contracted Covid-19, to date.

Earlier this month, another study by Chinese researchers found that the coronavirus incubation period can be up to 24 days, contrary to the previously believed 14 days.

18 FEBRUARY 2020

EC grants approval to Novartis’ Beovu to treat wet AMD

The European Commission (EC) has approved Novartis’ Beovu (brolucizumab) injection to treat wet age-related macular degeneration (AMD).

Wet AMD is a degenerative eye disease that develops due to excess vascular endothelial growth factor (VEGF) protein, which promotes the growth of abnormal blood vessels below the macula area of the retina.

Beovu is a humanised single-chain antibody fragment (scFv) with high affinity to all VEGF-A isoforms. It is said to be the first anti-VEGF drug approved by the EC that enables three-month dosing intervals immediately following the loading phase.

Novartis Pharmaceuticals president Marie-France Tschudin said: “Currently, wet AMD patients, who are often older, can face significant challenges in managing their disease.

“We believe that Beovu, and its ability to resolve fluid, brings great therapeutic value that will help physicians optimise treatments for patients based on disease activity.”

The EC approval comes after the review of data from the Phase III HAWK and HARRIER clinical trials, where the drug met the primary endpoint with non-inferior gains in best-corrected visual acuity (BCVA), compared to aflibercept at year one.

Data showed that the vision gains were maintained at year two, demonstrating better outcomes on fluid-related secondary endpoints at week 16 and year one.

The company notes that more than 50% of trial participants were treated on the three-month dosing period at year one, while the remaining were on a two-month interval.

Beovu obtained the US Food and Drug Administration (FDA) approval to treat wet AMD in October. FDA approval also came from HAWK and HARRIER results.

Last month, the drug secured approvals from the Swiss Agency for Therapeutic Products and Australian Therapeutic Goods Administration for the treatment of wet AMD.

17 FEBRUARY 2020

Takeda’s SC Entyvio meets primary endpoint in Crohn’s Disease

At the European Crohn’s and Colitis Organization (ECCO) congress in Vienna, Austria, Takeda announced the subcutaneous (SC) formulation of Entyvio (vedolizumab) met its primary endpoint in Crohn’s Disease.

In the Phase III VISIBLE 2 trial, the primary endpoint was clinical remission at week 52; 48% of the Entyvio group met this endpoint, compared to 34.3% of the placebo group. SC Entyvio was administered at week six and then every two weeks up to week 50; it was preceded by two doses of the intravenous (IV) formulation of Entyvio.

The IV formulation of this humanized monoclonal antibody has marketing authorisation in more than 60 countries and is specifically for patients with an inadequate response with, lost response to, or intolerance to corticosteroids, immunomodulators or a tumor necrosis factor-alpha (TNFα)-antagonist.

Honorary member of ECCO and Katholieke Universiteit Leuven Chronic Diseases and Metabolism department head Séverine Vermeire said: “The VISIBLE 2 study showed that the investigational SC formulation of vedolizumab helped patients with moderately to severely active Crohn’s disease achieve clinical remission at week 52, after first responding to induction therapy with IV vedolizumab.

“These results suggest that the investigational SC formulation of gut-selective vedolizumab can provide a new treatment modality for patients who might prefer a therapy that can be self-administered outside of the hospital setting.”

University of California, San Diego, Inflammatory Bowel Disease Centre director William Sandborn added: “These data indicate that the investigational subcutaneous formulation of vedolizumab seems to have a similar safety profile to the intravenous formulation.

“If approved, subcutaneous vedolizumab, together with the intravenous formulation, could provide more choice to patients in how they receive their therapy, helping to meet their individual needs and preferences.”

The IV formulation of Entyvio has been associated with infusion-related reactions, which can be severe and cause an anaphylactic reaction.

Takeda also presented the results from its secondary endpoints at the ECCO congress, including clinical response rate; 52% of the Entyvio group achieved this at week 52, compared to 44.8% of placebo group. Although there is a higher response rate, the difference is not statistically significant.

In addition, the Japanese pharma company performed analysis of certain patient sub-groups included in the trial. VISIBLE 2 studied the use of SC Entyvio during maintenance therapy of either corticosteroids, immunomodulators or TNFα-antagonist.

In patients who received corticosteroid treatment at baseline, 45.3% of patients who achieved corticosteroid-free clinical remission rate at week 52, compared to 18.2% in the placebo group.

The Phase III trial also studied patients who were naïve to treatment with TNFα therapy; 48.6% of the Entyvio group reached clinical remission at week 52, compared to 42.9% of the placebo arm.

14 FEBRUARY 2020

Preclinical data of Gilead’s remdesivir raises hope for China trials

A study by the US National Institutes of Health (NIH) has demonstrated that Gilead’s antiviral drug, remdesivir, could prevent a type of coronavirus in monkeys.

Data showed that the drug prevented the Middle East respiratory syndrome coronavirus (MERS-CoV) disease when administered before infection. In infected animals, remdesivir improved their condition.

NIH noted that these results support testing of the drug against the new coronavirus that emerged in China last month, as MERS-CoV is closely related to SARS-CoV-2.

Remdesivir was originally developed to fight Ebola. Previous tests in monkeys show that the drug is an effective treatment for Ebola and Nipah viruses.

The latest study at the National Institute of Allergy and Infectious Diseases (NIAID)’s Rocky Mountain Laboratories in Hamilton, Montana assessed the drug for the treatment of MERS coronavirus.

During the study, all untreated control animals exhibited signs of respiratory disease, while those treated 24 hours before the infection had no signs of respiratory infection or lung damage, along with lower levels of virus replication.

Compared to the control animals, those treated 12 hours after infection also showed less severe disease, lower virus levels in lungs and less lung damage.

In a statement, NIH said: “The scientists indicate that the promising study results support additional clinical trials of remdesivir for MERS-CoV and 2019-nCoV.

“At least two clinical trials of remdesivir for 2019-nCoV are underway in China, and other patients with 2019-nCoV infection have received the drug under a compassionate use protocol.”

The Biomedical Advanced Research and Development Authority (BARDA) of the US Department of Health and Human Services supported the study, along with Gilead.

NIAID published the study findings in the Proceedings of the National Academy of Sciences.

13 FEBRUARY 2020

Merck’s Keytruda achieves PFS in Phase III TNBC study

Merck has announced Keytruda (pembrolizumab) combined with chemotherapy met one of two primary endpoints, progression-free survival (PFS), in the Phase III KEYNOTE-355 study of triple negative breast cancer (TNBC) patients.

According to interim analysis by an independent data monitoring committee (DMC), Keytruda plus investigator’s choice of one of three types of chemotherapy – nab-paclitaxel, paclitaxel or gemcitabine/carboplatin – achieved statistically significant and clinically meaningful improvement in PFS compared to chemotherapy alone.

The other primary endpoint is overall survival (OS), which will be evaluated in the next DMC’s analysis. Other secondary endpoints of the KEYNOTE-355 study were overall response rate, duration of response and disease control rate.

Merck president Dr Roger M Perlmutter said: “Triple-negative breast cancer is an aggressive malignancy. It is very encouraging that Keytruda in combination with chemotherapy has now demonstrated positive results as both a first-line treatment in the metastatic setting with this trial, and as neoadjuvant therapy in the KEYNOTE-522 trial.

“We look forward to sharing these findings with the medical community at an upcoming congress and discussing them with the FDA and other regulatory authorities.”

The KEYNOTE-355 study was composed of two parts – the first was open label and focused on 30 patients, whereas the second was placebo-controlled and randomised, and had 847 patient participating.

Keytruda is anti-programmed cell death-1 (PD-1) therapy, which activates T lymphocytes against tumours. TNBC does not test positive for oestrogen receptor, progesterone receptor or human epidermal growth factor receptor 2, which are the primary targets of breast cancer treatments.

Merck’s therapy is approved in 13 different types of cancer, as well as many sub-types. Other studies in the company’s TNBC clinical development programme are KEYNOTE-242 and KEYNOTE-522.

The company announced interim independent DMC analysis for KEYNTOE-522 in July 2019. Keytruda combined with chemotherapy met one of two primary endpoints, pathological complete response, following neoadjuvant regimen. The other co-primary endpoint is PFS, and results will be published at a later date.

12 FEBRUARY 2020

Native Antigen Company unveils novel coronavirus antigens

UK-based The Native Antigen Company has commercially introduced novel coronavirus antigens to help fight the ongoing epidemic.

The recombinant antigens were obtained from the strain, emerged in Wuhan, China, by using the company’s mammalian, VirtuE expression system.

These antigens help in infectious disease research, as well as the development of diagnostics and vaccines.

The Native Antigen Company commercial director Dr Andy Lane said: “Our mission is to reduce the global burden of infectious disease by developing the highest-quality reagents in rapid response to emerging public health threats.

“As one of the first recognised suppliers to release 2019-nCoV proteins, we are proud to be able to offer these antigens to in vitro diagnostics and pharmaceutical researchers to help drive the development of serological assays and vaccines that will be vital in stemming the spread of this disease.”

Antigens facilitate the development of serological assays to detect asymptomatic patients. They can also provide reagents to measure vaccine responses, aiding the construction of a vaccine against the virus.

Last month, researchers at the Peter Doherty Institute for Infection and Immunity in Australia recreated a lab-grown version of the new coronavirus.

12 FEBRUARY 2020

Pfizer and Astellas report OS data for Xtandi in non-metastatic CRPC

Japanese company Astellas and US-headquartered Pfizer have announced final overall survival (OS) for Xtandi (enzalutamide) in non-metastatic castration-resistant prostate cancer (nmCRPC).

Xtandi is being studied in this patient group alongside androgen deprivation therapy (ADT) in the Phase III PROSPER trial. The drug demonstrated statistically significant improvement in OS – the key secondary endpoint in the study – compared to placebo plus ADT.

Detailed safety and efficacy results from the final PROPSER OS analysis will be shared at a later date. Other secondary endpoints in the study are time to prostate-specific antigen (PSA) progression and time to use antineoplastic therapy.

This announcement follows on from 2018 primary endpoint PROSPER results of metastasis-free survival. It was measured from the time that participants entered the trial to until their cancer was radiographically detected as having metastasised or they died within 112 days of treatment discontinuation. These results were presented at the Genitourinary Cancers Symposium, and then published in the New England Journal of Medicine.

Xtandi is an androgen receptor indicator, which was approved for nmCRPC in July 2018 by the US Food and Drug Administration (FDA). This made it the first FDA-approved drug for both nmCRPC and mCRPC; it was approved for the latter in 2012.

Prostate Cancer Foundation president and CEO Jonathan Simmons commented: “With today’s approval, there is now a new option for men with non-metastatic CRPC, who are in between the failure of androgen deprivation therapy resulting in CRPC and the onset of metastatic disease.”

The drug is also approved for nmCRPC in Europe and Japan; it is currently under review in China.

CRPC is a subset of men whose PC progresses although they are taking ADT and have castrate levels of testosterone. nmCRPC means the cancer has not spread to other parts of the body and there is a rising PSA level; many nmCRPC patients with a rising PSA level quickly develop mCRPC.

The drug has also been approved for metastatic castration-sensitive prostate cancer, and is being studied in the Phase III ARCHES trial in patients with metastatic hormone-sensitive, but not yet resistant, prostate cancer.

Astellas and Pfizer initiated their global agreed to develop and commercialise enzalutamide in October 2009. They jointly commercialise Xtandi in the US, while Astellas alone commercialises the drug outside of the US.

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