19 MAY 2020

Cipla to explore remdesivir multi-drug combination for Covid-19

India-based Cipla has plans to explore the use of multi-drug combination, including Gilead Sciences’ investigational antiviral drug remdesivir, for the treatment of Covid-19 coronavirus infection.

In an interview with Livemint news agency, Cipla chief financial officer Kedar Upadhye said that the company intends to assess a combination of zinc, hydroxychloroquine, azithromycin, lopinavir-ritonavir and favipiravir, among other drugs.

Upadhye was quoted as saying: “We are trying all avenues. We are attempting to come to the service of patients and try to see which molecule is more effective. We are trying through all ways. I think we will attack Covid-19 through multiple ways.”

Cipla is among the five companies that entered a non-exclusive licensing agreement with Gilead last week to manufacture and distribute remdesivir for Covid-19 patients in 127 countries, including India and South Africa.

The company also exclusively markets Roche’s rheumatoid arthritis drug Actemra, under the brand name tocilizumab, in India. The anti-inflammatory drug is currently being tested as potential Covid-19 treatment in India as well as international markets.

Upadhye noted: “Cipla is the sole agent of Roche’s anti-inflammatory drug Actemra in India, which can be used in patients with severe lung problems.

“It is one of the possible treatment options being explored for Covid-19 in addition to remdesivir, favipiravir, and lopinavir and ritonavir. The drug (Actemra) is currently undergoing clinical trials worldwide.”

Last month, the Indian Institute of Chemical Technology (IICT) announced the transfer of its process to produce favipiravir to Cipla, along with significant quantities of active pharmaceutical ingredients.

Livemint added that Cipla is seeking the Drug Controller General of India (DCGI) approval to launch favipiravir in India. The company plans to conduct a clinical trial prior to potentially marketing the antiviral drug under the brand Ciplenza.

18 MAY 2020


AstraZeneca gets breakthrough status for Enhertu to treat NSCLC

AstraZeneca and its partner Daiichi Sankyo have received breakthrough therapy designation (BTD) from the US Food and Drug Administration (FDA) for Enhertu (trastuzumab deruxtecan) to treat non-small cell lung cancer (NSCLC).

Approval is for patients with metastatic NSCLC tumours having a HER2 mutation with disease progression on or following platinum-based treatment.

Enhertu is a HER2-directed ADC that delivers cytotoxic chemotherapy to cancer cells through a linker attached to a monoclonal antibody that binds to a target expressed on cancer cells.

In the US and Japan, the drug has the approval to treat adults with a specific type of unresectable or metastatic HER2-positive breast cancer.

AstraZeneca and Daiichi Sankyo partnered in March last year for the development and commercialisation of the drug globally, except in Japan where Daiichi Sankyo has exclusive rights.

Daiichi Sankyo Oncology R&D oncology development global head and senior vice-president Gilles Gallant said: “We are encouraged by the promising evidence of activity seen with Enhertu in patients with advanced lung cancer and a HER2 mutation.

“We look forward to working closely with the FDA on the potential for Enhertu to become the first HER2-directed therapy approved for non-small cell lung cancer.”

FDA breakthrough status is supported by results from the ongoing Phase II DESTINY-Lung01 trial in patients with HER2-mutant (HER2m) metastatic NSCLC, as well as a completed Phase I trial.

During the DESTINY-Lung01 trial, the drug’s overall safety and tolerability profile were found to be consistent with that of the Phase I trial.

Last week, the drug secured BTD in the US for patients with HER2-positive unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma after two or more prior regimens including trastuzumab.

In 2017, Enhertu secured BTD for HER2-positive metastatic breast cancer and received approval in December.

18 MAY 2020

Sorrento’s antibody completely blocks Covid-19 in-vitro

Sorrento Therapeutics has reported that its Covid-19 therapeutic antibody candidate, STI-1499, can completely block the viral infection in-vitro during preclinical studies.

The company intends to develop an antibody cocktail that would protect from Covid-19 and remain effective even if mutations make a single antibody less effective over time.

Sorrento has been diligently screening numerous antibodies in its G-MAB fully human antibody library and discovered hundreds of candidates that bind the S1 subunit of the SARS-CoV-2 Spike protein.

Of these antibodies, around 12 showed the ability to inhibit the interaction of the S1 protein with human angiotensin-converting enzyme 2 (ACE2) used for viral entrance into human cells.

The company analysed these antibodies for their ability to block Covid-19 in an in-vitro SARS-CoV-2 virus infection model. Of the antibodies with neutralising activity, STI-1499 could fully inhibit the infection of healthy cells at a significantly low dose.

In addition, early biochemical and biophysical analyses also demonstrated that STI-1499 could be a potentially strong antibody drug candidate.

Speaking of the development, Sorrento Therapeutics chairman and CEO Dr Henry Ji said: “Our STI-1499 antibody shows exceptional therapeutic potential and could potentially save lives following receipt of necessary regulatory approvals.

“We at Sorrento are working day and night to complete the steps necessary to get this product candidate approved and available to the waiting public.”

The company expects to use STI-1499 as the first antibody in the antibody cocktail, COVI-SHIELD. It will also be developed as a monotherapy, COVI-GUARD, due to its high potency demonstrated to date.

Sorrento’s antibody manufacturing facility in San Diego, US is estimated to have the ability to manufacture up to two hundred thousand doses per month. The aim is to produce up to a million doses at risk while seeking the US Food and Drug Administration (FDA) approval for any STI-1499 candidate.

15 MAY 2020

Oxford University’s Covid-19 vaccine shows promise in animal study

The University of Oxford in the UK has reported positive findings of its Covid-19 vaccine candidate in a small preclinical study involving six monkeys.

This preliminary data of the vaccine, currently in human trials, has been published on the preprint website bioRxiv, noted Reuters.

According to the publication, some monkeys administered with a single shot of the vaccine generated antibodies against the virus within 14 days while all monkeys developed antibodies within 28 days, prior to being exposed to high virus doses.

Following exposure to the coronavirus, the vaccine candidate prevented damage to the lungs and blocked the virus from replication. However, the virus was found to be actively replicating in the nose.

London School of Hygiene & Tropical Medicine pharmacoepidemiology professor Stephen Evans said that the animal data was "good news". Evans was quoted as saying: “It is one of the hurdles to be passed by the Oxford vaccine and it has cleared it well.”

The professor also noted that no evidence of immune-enhanced disease, where a vaccine makes the disease worse, was reassuring.

Evans added: “This was a definite theoretical concern for a vaccine against SARS-CoV-2 and finding no evidence for it in this study is very encouraging.”

Last month, the University of Oxford signed an agreement with AstraZeneca to develop and distribute its Covid-19 vaccine candidate, a recombinant adenovirus vaccine in development by Jenner Institute and Oxford Vaccine Group at the university.

Results from the human trial are expected next month, with plans to start late-stage trials by the middle of this year. As part of the deal, AstraZeneca will carry out the development and global manufacturing and distribution of the vaccine.

13 MAY 2020

FDA fast-tracks Moderna’s Covid-19 vaccine candidate

The US Food and Drug Administration (FDA) has awarded fast-track designation to Moderna mRNA vaccine candidate, mRNA-1273, developed to protect against Covid-19.

Fast-track designation enables development and speed-up of the review of therapies and vaccines that target serious conditions and fill an unmet medical need.

Programmes with the designation could see early and frequent communication with the FDA, along with a rolling submission of the marketing application.

Previously, Moderna obtained fast-track designation for its investigational Zika vaccine, methylmalonic acidemia and propionic acidemia programmes.

Moderna chief medical officer Tal Zaks said: “Fast-track designation underscores the urgent need for a vaccine against the novel coronavirus.

“As we await the full set of clinical data from the NIAID-led Phase I study, we are actively preparing for our Phase II and Phase III clinical studies to continue learning about the potential of mRNA-1273 to protect against SARS-CoV-2.”

The FDA completed its review of the investigational new drug (IND) filing for mRNA-1273 on 6 May, allowing the launch of a Phase II clinical trial.

The Phase II study will assess the safety, reactogenicity and immunogenicity of two vaccinations of mRNA-1273 administered 28 days apart. It will enrol 600 healthy volunteers aged 18 years and above.

Participants will be given placebo, a 50μg or a 250μg dose at both vaccinations and followed through 12 months following the second vaccination.

The company is finalising the protocol for a Phase III study. The Biomedical Advanced Research and Development Authority (BARDA) funding helped plan these studies and will support the late-stage clinical programmes.

In addition, the funding will be used to scale up manufacturing of the vaccine candidate at the company’s facilities and at that of its strategic partner, Lonza.

11 MAY 2020

Lilly secures FDA approval for Retevmo to treat lung/thyroid cancers

Eli Lilly has secured accelerated approval from the US Food and Drug Administration (FDA) for the use of Retevmo (selpercatinib) to treat lung and thyroid cancers.

The drug is indicated for metastatic rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC) in adults.

It is also meant for patients aged 12 years and above with advanced or metastatic RET-mutant medullary thyroid cancer (MTC) needing systemic therapy or advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and are radioactive iodine-refractory.

Retevmo is a selective RET kinase inhibitor that could act on tumour and healthy cells, which may cause side effects.

Lilly Oncology president Anne White said: “We are extremely proud of how quickly the combined Loxo Oncology and Lilly Oncology teams brought Retevmo to patients, further demonstrating our commitment to delivering life-changing medicines to people living with cancer.

“Retevmo entered clinical trials in May of 2017 and is now approved less than three years later, representing the most rapid timeline in the development of an oncology medicine with multiple indications.”

Retevmo was approved based on objective response rate (ORR) and duration of response (DoR) data from the Phase I/II LIBRETTO-001 clinical trial, which is a single-arm, multi-centre study performed in patients with RET-driven cancers.

The trial involved treatment-naive patients as well as heavily pretreated patients with various advanced solid tumours including RET fusion-positive NSCLC, RET-mutant MTC, RET fusion-positive thyroid cancer and other solid tumours with RET alterations.

LIBRETTO-001 lead investigator Alexander Drilon said: “In the clinical trial, we observed that the majority of metastatic lung cancer patients experienced clinically meaningful responses when treated with selpercatinib, including responses in difficult-to-treat brain metastases.

“The approval of selpercatinib marks an important milestone in the treatment of NSCLC, making RET-driven cancers now specifically targetable in the same manner as cancers with activating EGFR and ALK alterations, across all lines of therapy.”

The drug is currently being assessed in two Phase III confirmatory trials, LIBRETTO-431 and LIBRETTO-531.

11 MAY 2020

Sorrento and Mount Sinai to develop antibody cocktail against Covid-19

Sorrento Therapeutics has collaborated with Mount Sinai Health System to develop an antibody cocktail, COVI-SHIELD, for the potential treatment of Covid-19.

Researchers at the Icahn School of Medicine at Mount Sinai screened nearly 15,000 people who may have recovered from the novel coronavirus infection for the presence of anti-Covid-19 antibodies.

Sorrento will be able to access plasma containing anti-Covid-19 antibodies to identify and generate monoclonal antibodies that could potentially neutralise SARS-CoV-2 activity.

As part of the collaboration, Mount Sinai and Sorrento aim to develop antibodies that would be a ‘protective shield’ against Covid-19 by inhibiting and neutralising the virus’ activity in naïve at-risk populations, as well as recently infected patients.

Each COVI-SHIELD dose is expected to comprise a cocktail of three antibodies, which together could identify three different regions of the SARS-CoV-2 Spike protein.

Antibody cocktail therapy could prevent the development of treatment resistance. If approved, COVI-SHIELD will be given as a prophylactic for those individuals returning to work and as a therapeutic to people exposed to the virus.

Each dose of the antibody cocktail may deliver antiviral protection for up to two months.

Sorrento Therapeutics chairman and CEO Dr Henry Ji said: “It is our intention to develop a triple antibody prophylactic and therapeutic agent that would shield healthcare workers and at-risk patients.

“This therapy is designed to be resistant to future virus mutations and, if approved, should be made available in support of testing, tracing, vaccination and other therapeutic approaches to allow for efficient management of viral infection by protecting those most at risk for up to two months at a time.”

The company is in the process of filing investigational new drug (IND) applications for the triple antibody combination therapy and estimates to launch Phase I clinical trials in the third quarter of this year.

In March, Sorrento started a programme to develop a decoy cellular vaccine, STI-6991, against Covid-19.

08 MAY 2020

UK’s NICE recommends Roche breast cancer drug Kadcyla

The National Institute for Health and Care Excellence (NICE) in the UK has recommended the use of Roche’s Kadcyla (trastuzumab emtansine) to treat certain patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer.

Kadcyla is an antibody-drug conjugate (ADC) designed to deliver chemotherapy directly to HER2-positive cancer cells and reduce damage to healthy tissues. It received the European Commission approval in December last year.

Roche licenses the technology for the drug as part of an agreement with ImmunoGen.

NICE noted that approximately 7,000 people with early breast cancer have HER2-positive disease each year in England. HER2 is a protein found on the surface of cancer cells and helps them grow and divide.

Kadcyla is a targeted cancer drug. Trastuzumab binds to the HER2 receptor and enables entry of the emtansine into the cancer cell, where it becomes active and destroys the cancer cell.

Data from clinical trial revealed that trastuzumab emtansine improves the time patients remain free of disease compared to trastuzumab alone in people with some cancer cells remaining following chemotherapy and HER2-targeted therapy.

Evidence on trastuzumab emtansine’s ability to increase the length of time patients live is yet to be available.

Kadcyla list price is an average £51,000 per patient for a course of treatment. Roche entered a commercial arrangement to offer the drug to the NHS at an undisclosed discount.

NICE Centre for Health Technology Evaluation deputy chief executive and director Meindert Boysen said: “Additional treatment options that can increase the amount of time in which people remain free of disease after surgery, and perhaps stop it from coming back altogether, are particularly welcome.

“We are therefore pleased to be able to recommend that trastuzumab emtansine is made available routinely for people with HER2-positive early breast cancer after surgery.”

The pricing watchdog will publish its final draft guidance on Kadcyla next month.

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