Partially-vaccinated Fla. woman among first to birth baby with COVID antibodies

  Two pediatricians based in Boca Raton, Dr. Paul Gilbert and Dr. Chad Rudnick, have published a “pre-print” of the first case believed to be reported in the world of a baby born with antibodies to COVID-19.

“After the vaccine came out, we started looking for people who might be pregnant, who were eligible to get it,” said Gilbert. “We saw the recommendations changed pretty quickly to allow pregnant women to get the vaccine.

Gilbert and Rudnick wrote up a case report, saying a pregnant woman received a single dose of the Moderna COVID-19 vaccine. They said three weeks later, she gave birth to a healthy baby girl, who they claim had antibodies against COVID.

“Coming into January, we had the opportunity with a healthcare worker for her to get her vaccine at the end of her pregnancy and then when the baby was born, we were able to test that baby’s cord blood to look for antibodies that were made from the vaccine to see if those antibodies passed from the mom to the baby and potentially give the baby protection,” said Gilbert.

“We were fortunate this was essentially an opportunity study, because of the time this healthcare worker was able to receive her first vaccine, it was early on in the vaccine rollout,” said Rudnick. “It was the first case to our knowledge that was reported in the literature around the world, of a baby born to a mother who had not had COVID previously, and then was vaccinated and then see that they had antibodies.”

The two doctors said because of what they know about antibody transmission to a fetus during pregnancy, this was expected.

“We were very excited to see once the test result came back, that the antibodies from the mom’s vaccine did in fact pass through the plancenta to the newborn,” he said.

They hope this now leads to further studies of maternal COVID vaccinations to protect babies as well.

For both doctors, they said they’re excited at what they believe is the first in the world in our backyard, and a positive in the midst of the pandemic. Right now, Gilbert and Rudnick said they’re in the final phase to get formal publication.

They’re excited at what they believe is the first reported case in the world and a positive in the midst of the pandemic. Right now, they said they’re in the final phase to get formal publication.

“Really cool great scientific opportunity and we knew that we were going to be potentially one of the first in the world to report it and that opportunity probably only comes once in a career,” said Gilbert.

“Being able to report something that is the first in the world in literature is something that does not come up in most careers,” said Rudnick.

https://www.wptv.com/coronavirus/boca-raton-partially-vaccinated-woman-among-first-to-birth-baby-with-covid-antibodies

Novartis says £1.8m Zolgensma is model for gene therapy pricing

 Novartis has said its gene therapy pricing model, involving a steep one-off payment, could be a template for the hundreds of similar treatments that could follow its Zolgensma for Spinal Muscular Atrophy (SMA). 

Zolgensma (onasemnogene abeparvovec) has a list price of £1,795,000 excluding VAT in the UK, but Novartis says the price is justified by the clinical data it has gathered, showing the treatment is particularly effective at reducing symptoms in babies if given early.

The data were strong enough to convince NICE and the Scottish Medicines Consortium to recommend NHS funding early last week in young babies, followed shortly after by Italy’s AIFA.

Germany was the first country in Europe to launch the drug under its AMNOG system last year, which allows for a year of free pricing before negotiations begin with the national health insurance system.

Despite the high initial outlay, Mike Fraser, general manager for Europe, Middle East and Africa at Novartis, said the successful launch of Zolgensma paves the way for other gene therapies in the pharma pipeline.

There are hundreds in development – including a clinical trial of an Alzheimer’s gene therapy in the US – and Fraser said the precedent has now been set with payers in Europe.

The decision to fund Zolgensma show payers are coming around to the idea of a one-off payment for a powerful therapies, as well as other innovative ideas such as annuity schemes and outcomes-based contracts.

He told pharmaphorum: “This is very different to the way the system is set up for chronic therapies. You have to convince the ecosystem to change the way it views therapies.

“The model is going to last for the long term. [Products] need to show value in terms of efficiencies and cost offsets. There are around 350 gene therapies in various studies.”

In the UK Novartis has negotiated a confidential discount with the NHS, but nevertheless it’s a bold move to reimburse the therapy.

Fraser told pharmaphorum that the decision was driven by the government’s drive to encourage pharma companies to research and launch novel therapies in the UK.

Support from patient groups and academic institutions helped to build the critical mass that led to funding approval, Fraser said.

“It was the UK leading the way. It’s not only collaboration with payers and NICE and NHS – patient advocacy groups were crucial to getting us across the finishing line.”

https://pharmaphorum.com/news/novartis-e1-9m-zolgensma-is/

GSK, German Merck's $4.2B bintrafusp alfa drug flops again

 Two months after GlaxoSmithKline and Merck KGaA’s oncology asset bintrafusp alfa failed to beat out King Keytruda in certain lung cancers, it has followed up with another disappointment.

The bifunctional fusion protein immunotherapy, which is the center of the $4.2 billion deal GSK penned with Merck in 2019, flopped a midstage test on its own treating 159 second-line patients with locally advanced or metastatic biliary tract cancer (BTC).

An independent review showed it had an objective response rate (ORR) of just 10.1% , with efficacy hitting below a predefined threshold that would have let it file the drug in that setting.

Merck is not throwing in the towel completely for this target, as an ongoing phase 2/3 study of bintrafusp alfa with chemo as a first-line treatment for BTC “is assessing a different hypothesis than the second-line monotherapy study,” according to a statement.

Despite the second-line flop, Merck still says it saw single-agent activity in a tough area; and, though it had a small ORR, this was better than what others had achieved.

“Given the high unmet treatment need in BTC, where single agent immunotherapy in PD-L1 all comers has shown an ORR of 5.8%, we are encouraged by the single agent clinical activity of bintrafusp alfa in this study as a second-line treatment,” said Milind Javle, M.D., professor of GI medical oncology at the MD Anderson Cancer Center and an investigator for the INTR@PID BTC 047 study.

“The bintrafusp alfa 047 study is one of the most important clinical investigations conducted for chemo-refractory biliary cancers, and I would like to thank the patients, families, and study team for their valuable participation.”

“This study demonstrates single-agent activity with bintrafusp alfa in locally advanced or metastatic BTC, a disease that has been historically difficult to treat,” added Danny Bar-Zohar, M.D., global head of development for the healthcare business sector of Merck. “The data will contribute to our understanding of addressing both TGF-β and PD-L1 inhibition in the tumor microenvironment.”

The drug is designed to combine a TGF-β trap with the anti-PD-L1 mechanism in one fusion protein and to combine co-localized blocking of the two immuno-suppressive pathways. Targeting both pathways aims to control tumor growth by potentially restoring and enhancing anti-tumor responses.

This impressed GSK enough two years back to see the U.K. Big Pharma hand German Merck €300 million upfront with development milestone payments of up to €500 million and potential sales-related payments of €2.9 billion, which brought the total to an eye-watering figure of €3.7 billion ($4.16 billion).

But it’s not had a good run thus far: In January this year, in a late-stage test of the drug in PD-L1-expressing non-small cell lung cancer patients, an independent monitoring committee told the pair the drug will likely not hit its primary endpoint, which was progression-free survival, in the trial known as INTR@PID Lung 037.

The drug was going head-to-head with Merck’s rival U.S. pharma, also called Merck, and its winner-takes-all checkpoint inhibitor Keytruda, in newly diagnosed late-stage lung cancer patients. Beating out Keytruda, which has a strong track record in lung cancer, was always going to be a tough ask, and both companies were given some slack because of this.

Looking past a second failure just two months down the line, even in a tough-to-treat cancer, might be a bigger ask.

https://www.fiercebiotech.com/biotech/gsk-german-merck-s-4-2b-bintrafusp-alfa-drug-flops-again-but-companies-squint-to-see

Abu Dhabi's Mubadala interested in buying NMC hospital business

 Abu Dhabi’s sovereign fund Mubadala is considering buying NMC Health’s core hospital business, three sources familiar with the matter told Reuters, emerging as another suitor of the troubled hospital group.

NMC, the largest private healthcare provider in the United Arab Emirates, ran into trouble last year after the disclosure of more than $4 billion in hidden debt left a many UAE and overseas lenders with heavy losses.

The company, now in administration, is exploring the possibility of selling its healthcare business in the UAE and Oman, which sources have previously said could generate around $1 billion.

Mubadala, which has over $230 billion in assets under management, is one of the investors and companies looking at the asset, said the sources.

“As an investor we regularly assess opportunities for their potential fit into our portfolio,” a source close to Mubadala told Reuters.

Other suitors include Abu Dhabi state-owned holding company ADQ and Europe’s largest private equity firm CVC, Reuters reported earlier this month.

Sources have told Reuters the potential sale is a price discovery exercise to determine whether NMC’s business can get the value its creditors seek, or whether the business should keep the assets, complete the restructuring, and sell when they can achieve the value they want.

https://www.reuters.com/article/nmc-mubadala-ma/rpt-abu-dhabis-mubadala-interested-in-buying-nmc-hospital-business-sources-idUSL1N2LE0OT

Moderna: First Participants Dosed in Phase 2/3 Study of Pediatric COVID Vax Candidate

  Moderna Inc. (Nasdaq: MRNA), a biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines, today announced that the first participants have been dosed in the Phase 2/3 study, called the KidCOVE study, of mRNA-1273, the Company’s vaccine candidate against COVID-19, in children ages 6 months to less than 12 years. The study is being conducted in collaboration with the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH) and the Biomedical Advanced Research and Development Authority (BARDA), part of the Office of the Assistant Secretary for Preparedness and Response at the U.S. Department of Health and Human Services.

“We are pleased to begin this Phase 2/3 study of mRNA-1273 in healthy children in the U.S. and Canada and we thank NIAID and BARDA for their collaboration,” said Stéphane Bancel, Chief Executive Officer of Moderna. “It is humbling to know that 17.8 million adults in the U.S. have received the Moderna COVID-19 Vaccine to date. We are encouraged by the primary analysis of the Phase 3 COVE study of mRNA-1273 in adults ages 18 and above and this pediatric study will help us assess the potential safety and immunogenicity of our COVID-19 vaccine candidate in this important younger age population.”

This Phase 2/3 two-part, open label, dose-escalation, age de-escalation (Part 1) and randomized, observer-blind, placebo-controlled expansion study (Part 2) will evaluate the safety, tolerability, reactogenicity and effectiveness of two doses of mRNA-1273 given 28 days apart. The Company intends to enroll approximately 6,750 pediatric participants in the U.S. and Canada ages 6 months to less than 12 years.

In Part 1, each participant ages two years to less than 12 years may receive one of two dose levels (50 μg or 100 μg). Also in Part 1, each participant ages six months to less than 2 years may receive one of three dose levels (25 μg, 50 μg and 100 μg). An interim analysis will be conducted to determine which dose will be used in Part 2, the placebo-controlled expansion portion of the study. Participants will be followed through 12 months after the second vaccination. Vaccine effectiveness will either be inferred through achieving a correlate of protection, if established, or through immunobridging to the young adult (ages 18-25) population. Evaluation of vaccine safety and reactogenicity is also a primary endpoint of the study. The ClinicalTrials.gov identifier is NCT04796896. For more information about the trial, including the process for enrolling participants, please visit www.kidcovestudy.com.

https://www.biospace.com/article/releases/moderna-announces-first-participants-dosed-in-phase-2-3-study-of-covid-19-vaccine-candidate-in-pediatric-population/

FibroGen Initiates Second Phase 3 Study of Pamrevlumab for Duchenne

 FibroGen, Inc. (NASDAQ: FGEN) announced the initiation of LELANTOS-2, a Phase 3, randomized, double-blind, placebo-controlled trial of pamrevlumab or placebo in combination with systemic corticosteroids in patients with ambulatory Duchenne muscular dystrophy (DMD).

The primary objective of this global study is to evaluate the effect of pamrevlumab on muscle function in patients with DMD. Approximately 70 patients ages 6 to 12 years will be randomized 1:1 to receive pamrevlumab plus systemic corticosteroids, or placebo plus systemic corticosteroids every two weeks, for up to 52 weeks. The primary efficacy endpoint is ambulatory function assessment, measured by the change in North Star Ambulatory Assessment (NSAA) from baseline to Week 52. Additional secondary endpoints will be assessed in the study. Subjects who complete the 52-week study will be eligible for rollover into an open-label extension study with pamrevlumab and systemic corticosteroids. For more information about LELANTOS-2 please visit www.clinicaltrials.gov (NCT04632940).

“Duchenne, the most common form of muscular dystrophy in children, is typically diagnosed by 2-6 years of age and progresses rapidly, resulting in the loss of independent motor function by the early teenage years,” said Elias Kouchakji, M.D., Senior Vice President, Clinical Development, Drug Safety, and Pharmacovigilance, FibroGen. “The initiation of LELANTOS-2, the second Phase 3 clinical trial in the pamrevlumab clinical development program, underscores our commitment to delivering a meaningful treatment for DMD, an area with high unmet medical need.”

Pamrevlumab is a first-in-class antibody developed by FibroGen to inhibit the activity of connective tissue growth factor (CTGF), a common factor in fibrotic and proliferative disorders characterized by persistent and excessive scarring that can lead to organ dysfunction and failure. Importantly, skeletal muscle from DMD patients shows elevated levels of CTGF, and a major manifestation of DMD is cardiac fibrosis.

“The initiation of our second Phase 3 study of pamrevlumab for DMD furthers our research on the clinical benefits of inhibiting connective tissue growth factor, an important biological mediator in fibrotic and proliferative disorders,” said Mark Eisner, M.D, M.P.H, Chief Medical Officer, FibroGen. “We are committed to advancing the science of CTGF biology and evaluating clinical benefit in diverse diseases with unmet medical need, including idiopathic pulmonary fibrosis, locally advanced unresectable pancreatic cancer and Duchenne muscular dystrophy.”

https://www.biospace.com/article/releases/fibrogen-initiates-lelantos-2-second-phase-3-clinical-study-of-pamrevlumab-for-the-treatment-of-duchenne-muscular-dystrophy/

Roche launches SARS-CoV-2 variant test

 Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced

the launch of the cobas(R) SARS-CoV-2 Variant Set 1 Test to detect and 
differentiate mutations found in variants that originated in the UK 
(B.1.1.7), South Africa (B.1.351), and Brazil (P.1). This research use 
only laboratory test can be used to help scientists track mutation 
prevalence and to assess any potential impact on diagnostics, vaccines 
and therapeutics, providing crucial insight for healthcare systems in 
making appropriate measures to combat COVID-19. 
 
 
 
   Variants of B.1.1.7, B.1.351 and P.1 lineage gained prominence in late 
2020, with each carrying a number of genomic mutations. Among them, 
mutations E484K, N501Y and del 69-70 are located in the spike protein, 
the region that enables the virus to attach to and enter the human cell. 
Studies have suggested that these mutations may be linked to increased 
disease transmissibility, and possibly decreased therapeutic and vaccine 
efficacy.(1-4) 
 
 
 
   "Viruses naturally evolve over time. While most mutations do not have a 
clinical impact, some variants need to be tracked carefully as they seem 
to spread more easily and quickly," said Thomas Schinecker, CEO Roche 
Diagnostics. "Continued surveillance is essential for public health. Our 
latest solution provides laboratories a fast and efficient way to 
investigate these variants found in infected individuals and the 
potential impact on existing therapies, vaccines and tests." 
 
 
 
   The cobas SARS-CoV-2 Variant Set 1 Test runs on the widely available, 
high-volume cobas(R) 6800/8800 Systems. Pre-optimised assay design, 
ready-to-use test cassettes and predefined software parameters enable 
laboratories to reduce testing complexity and increase walkaway time. 
 
 
 
   It is important to note that Roche has confirmed its existing diagnostic 
tests to detect SARS-CoV-2 are not affected by known mutations and 
remain accurate and effective in detecting active infections. The 
company is conducting assessments on a regular basis and will continue 
to monitor as new variants arise. 
 
 
 
   About SARS-CoV-2 Variants B.1.1.7, B.1.351 and P.1 
 
   First reported in the UK in December 2020, B.1.1.7 variant has quickly 
become the dominant circulating variant and has since been found in 
countries worldwide.(1) B.1.1.7 carries a large number of mutations, 
eight of which are accumulated in the spike region. Preliminary studies 
have suggested that two such spike mutations, N501Y and del 69-70, are 
associated with increased transmissibility of the disease.(2,3) Another 
variant, B.1.351, which arose independently from B.1.1.7, was reported 
in South Africa in December 2020. In addition to having mutation N501Y, 
B.1.351 carries another spike mutation E484K, which appears to evade the 
body's immune response, possibly diminishing vaccine efficacy.(4) 
Variant P.1, a close relative to B.1.351, has several defining mutations 
including N501Y and E484K in the spike region. P.1 has been circulating 
in the Amazon region as of late 2020 and is thought to evade immunity 
generated after infection by other variants.(5) 
 
 
 
   About cobas SARS-CoV-2 Variant Set 1 Test 
 
   cobas SARS-CoV-2 Variant Set 1 Nucleic Acid test for use with the cobas 
6800/8800 Systems is an automated, multiplex, real-time reverse 
transcription polymerase chain reaction (RT-PCR) assay for the rapid in 
vitro qualitative detection and discrimination of select SARS-CoV-2 
mutations E484K, N501Y and del 69-70. The test contains the respective 
primers and probes provided in the ready-made 384-test cassette. 
Automated data management is performed by the cobas 6800/8800 software, 
which assigns test results for all tests. Results can be reviewed 
directly on the system screen, and printed as a report. Roche is 
committed to providing additional variant tests as needed based on 
regular assessments of the infectious disease landscape. 
 
 
 
   About cobas 6800/8800 Systems 
 
   When every moment matters, the fully automated cobas 6800/8800 Systems 
offer the fastest time to results with the highest throughput and the 
longest walk-away time available among automated molecular platforms. 
With proven performance, absolute automation and unmatched flexibility 
delivering unparalleled throughput 24/7-- cobas 6800/8800 Systems are 
designed to ensure a lab's long-term sustainability and success now, 
more than ever. Learn more now: www.cobas68008800.com. 
 
 
 
   About Roche's response to the COVID-19 pandemic 
 
   As a leading healthcare company we are doing all we can to support 
countries in minimising the impact of COVID-19. We have developed a 
growing number of diagnostic solutions that help to detect and diagnose 
the infection in patients, as well as providing digital support to 
healthcare systems, and we continue to identify, develop and support 
potential therapies which can play a role in treating the disease. 
 
 
 
   We understand the impact of COVID-19 goes beyond those who contract it, 
which is why we are working with healthcare providers, laboratories, 
authorities and organisations to help make sure that patients continue 
to receive the tests, treatment and care they need during these 
challenging times. As we learn from the pandemic, we are partnering with 
governments and others to make healthcare stronger and more sustainable 
in the future. 
 
 
 
   Our diagnostics solutions: 
 
   Reliable, high-quality testing is essential to help healthcare systems 
overcome this pandemic. Our portfolio includes: 
 
 
   -- a high-volume molecular test to detect SARS-CoV-2, the virus that causes 
      COVID-19, (FDA Emergency Use Authorisation (EUA) and available in 
      countries accepting the CE Mark) 
 
   -- a SARS-CoV-2 laboratory-based antibody test, aimed at detecting the 
      presence of antibodies in the blood targeting the nucleocapsid (FDA EUA 
      and CE Mark) 
 
   -- an IL-6 test to assist in identifying severe inflammatory response in 
      patients with confirmed COVID-19 (FDA EUA and CE Mark) 
 
   -- Roche v-TAC, which could help simplify the screening, diagnosis and 
      monitoring of patients with respiratory compromise in the current 
      COVID-19 pandemic 
 
   -- a SARS-CoV-2 rapid antibody test to help determine at the point of care 
      whether a person has been exposed to the virus (CE Mark) 
 
   -- a rapid antigen test to support in the detection of SARS-CoV-2 at the 
      point of care within 15 minutes (CE Mark) 
 
   -- a high-volume molecular test to simultaneously detect and differentiate 
      between SARS-CoV-2 and influenza A/B, as the symptoms are similar for 
      both (FDA EUA and CE Mark) 
 
   -- a second SARS-CoV-2 antibody test, aimed at measuring the spike protein 
      to support vaccination development and complement our existing portfolio 
 
   -- a point-of-care molecular PCR test that simultaneously detects and 
      differentiates between SARS-CoV-2 and influenza A/B infections to support 
      urgent triage and diagnosis (FDA EUA and CE Mark) 
 
   Our research into therapies 
 
 
 
   Roche is committed to improving the treatment of COVID-19. We are 
actively involved in understanding the potential of our existing 
portfolio and are exploring the potential of our investigational 
molecules. 
 
   In August we signed a collaboration agreement with Regeneron on 
developing and manufacturing and significantly increasing global supply 
of an investigational antibody combination for COVID-19 if it proves 
safe and effective in clinical trials and regulatory approvals are 
granted. We are also partnering with Atea to jointly develop AT-527, an 
orally administered direct-acting antiviral (DAA) currently in Phase 2 
clinical trials. If approved, Atea will distribute AT-527 in the United 
States and Roche will be responsible for global manufacturing and 
distribution outside the United States. 
 
   At the beginning of the pandemic, on 19 March, we announced the 
initiation of COVACTA - a global Phase III randomised, double-blind, 
placebo-controlled clinical trial to evaluate the safety and efficacy of 
intravenous Actemra(c)/RoActemra(c) (tocilizumab) plus standard of care 
in hospitalised adult patients with severe COVID-19 pneumonia compared 
to placebo plus standard of care. On 29 July we announced that COVACTA 
did not meet its primary endpoint of improved clinical status in 
patients with COVID-19 associated pneumonia or the key secondary 
endpoint of reduced mortality. 
 
   Separately, we have studied Actemra(c)/RoActemra(c) in the EMPACTA study 
in COVID-19 associated hospitalised pneumonia in patients that are often 
underrepresented in clinical trials. On 18 September we announced that 
the phase III EMPACTA study showed Actemra/RoActemra plus standard of 
care reduced the likelihood of progression to mechanical ventilation or 
death in hospitalised patients with COVID-19 associated pneumonia 
compared to placebo plus standard of care. However, there was no 
statistical difference in mortality between patients who received 
Actemra/RoActemra or placebo. 

https://www.marketscreener.com/quote/stock/ROCHE-HOLDING-AG-9364975/news/Press-Release-nbsp-Roche-launches-SARS-CoV-2-variant-test-to-help-monitor-emerging-coronavirus-mut-32693153/