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Monday, February 1, 2021

China's Clover ends COVID-19 vaccine partnership with Glaxo

 Clover Biopharmaceuticals has ended its partnership with GlaxoSmithKline Plc to develop a COVID-19 vaccine using its adjuvant, the Chinese drugmaker said on Monday, as it will stick with a vaccine booster from U.S.-based Dynavax instead.

The decision marks a further setback to GSK which said in December that clinical trials of a rival COVID-19 vaccine developed with partner Sanofi showed an insufficient immune response in older people and they decided to delay its launch.

Clover has been testing two COVID-19 vaccine candidates, one containing an adjuvant, typically designed to boost the efficacy of vaccines, from GSK, and the other from Dynavax Technologies Corp.

While both candidates induced high levels of neutralizing antibodies, Clover said it decided to initiate Phase II and III studies of the candidate using the Dynavax adjuvant after taking into account "scale-up manufacturing considerations."

"Having fully evaluated all available data, and based on our discussions with Clover and CEPI, we will not progress this collaboration using GSK's pandemic adjuvant," a GSK representative said in an emailed response to Reuters.

The Coalition for Epidemic Preparedness Innovations (CEPI), a global epidemic response group, is funding the Phase II/III trial of Clover's vaccine.

CEPI separately on Monday agreed to provide Dynavax funding of up to $99 million to manufacture its adjuvant or vaccine booster for COVID-19 vaccine developers that CEPI has funded.

Shares of Dynavax rose nearly 15% before the trading bell.

A Clover representative said GSK and the company will "move forward with other collaborations that they believe will be able to maximize their respective and overall impacts against the COVID-19 pandemic."

The mid-to-late stage trial of its candidate with the Dynavax's adjuvant will start in the first half of this year, with interim analysis of its efficacy expected around in the middle of 2021, Clover said. 

https://www.marketscreener.com/quote/stock/DYNAVAX-TECHNOLOGIES-CORP-19120561/news/China-s-Clover-ends-COVID-19-vaccine-partnership-with-GSK-32324306/

Bayer agrees to help make CureVac's COVID-19 vaccine

 German pharmaceutical giant Bayer said on Monday it will help CureVac produce its experimental COVID-19 vaccine, the latest drugmaker to offer up manufacturing capacity as supplies fall behind demand.

Bayer said it expects to produce 161 million doses of CureVac’s experimental vaccine, which is currently in late-stage testing, in 2022, its head of pharma Stefan Oelrich told a news conference.

https://www.reuters.com/article/us-health-coronavirus-curevac-bayer/bayer-agrees-to-help-make-curevacs-covid-19-vaccine-idUSKBN2A11VX

Oxford kept COVID-19 vaccine trial volunteers in dark about dosing error

 About 1,500 of the initial volunteers in a late-stage clinical trial of the Oxford/AstraZeneca COVID-19 vaccine were given the wrong dose, but weren’t informed that a mistake had been made after the blunder was discovered, documents obtained by Reuters show.

Instead, the dosing mishap was presented to the trial participants in a letter dated June 8 as an opportunity for University of Oxford researchers to learn how well the vaccine works at different doses. The letter was signed by the trial’s chief investigator, Oxford professor Andrew J. Pollard, and sent to the trial subjects.

As Reuters reported on Dec. 24, participants were given about a half dose due to a measuring mistake by Oxford researchers. The Pollard letter didn’t acknowledge any error. Nor did it disclose that researchers had reported the issue to British medical regulators, who then told Oxford to add another test group to receive the full dose, in line with the trial’s original plan.

There is no suggestion there was any risk to the health of trial participants.

Much is riding on the British-developed vaccine, which is being rolled out across the UK and has been touted as a low-cost weapon against the pandemic. The jab has come under scrutiny because of the dosing error in the Oxford trial and a paucity of data about its efficacy in older people who are most vulnerable to the virus.

Reuters shared the letter – which it obtained from the university through a Freedom of Information request – with three different experts in medical ethics. The ethicists all said it indicates the researchers may not have been transparent with trial participants. Volunteers in clinical trials are supposed to be kept fully informed about any changes.

“They are not clear at all about what they need to be clear about – what’s going on, what they knew, the rationale for undertaking further research,” said Arthur L. Caplan, founding head of the Division of Medical Ethics at New York University Grossman School of Medicine. “It is lost in a snowstorm of verbiage.”

Steve Pritchard, a spokesman for Oxford, told Reuters: “The half-dose group was unplanned, but we did know in advance that there was a discrepancy in the dose measurements and discussed this with the regulators before dosing and when the dosing was revised.”

Pritchard also said, “We have not stated that a dosing error occurred.”

Pollard didn’t respond to a request for comment.

The spokesman’s suggestion that no error was made is contradicted by documents produced last year by Oxford and its vaccine partner, drugs giant AstraZeneca PLC. In December, Reuters reported that a “Global Statistical Analysis Plan” by Oxford/AstraZeneca, dated Nov. 17 and later published in the scientific journal The Lancet, called the dosing discrepancy “a potency miscalculation.”

A spokesman for AstraZeneca declined to comment.

The Health Research Authority, a British government agency responsible for approving medical research and ensuring it is ethical, said in a statement that changes to the study design and the letter sent to participants were approved by one of its ethics committees.

The Oxford/AstraZeneca vaccine recently has received authorization for use in a growing number of countries, including the United Kingdom, the European Union and India. The UK became the first country to approve it, and began rolling out the vaccine on January 4.

But questions surrounding the clinical trials continue to plague the vaccine. Last week, Germany’s vaccine committee recommended it should only be given to people aged under 65, while the EU, which authorized it on Friday for people aged 18 and over, lowered its reported efficacy rate from 70.4% to 60%. In both cases, authorities cited a lack of sufficient data from the clinical trials. The EU also has sharply criticized AstraZeneca for cutting back its planned vaccine deliveries to the continent over the next few months. The company has said it is doing its best to boost supplies.

The mistaken half-dose – which prompted the letter in June to trial participants – continues to be a factor in the reported efficacy of the Oxford/AstraZeneca vaccine.

Oxford had reported interim results in November that showed the efficacy rate for trial subjects who mistakenly received a half-dose and a subsequent full-dose booster shot was 90%, and that the rate for those who received two full doses was 62%. Combining data from the two dosing regimens resulted in an efficacy of 70.4%.

In authorizing the vaccine, UK regulator, the Medicines and Healthcare products Regulatory Agency (MHRA), accepted the pooled results, but didn’t approve administering the half-dose/full-dose regimen. “There is not persuasive evidence of a real difference in” vaccine efficacy between the two different dosing regimens, it said.

“RECENT CHANGES”

The vaccine’s late-stage clinical trial began on May 28. Within days, Oxford researchers realized trial participants had been given lower doses than planned after they displayed milder than expected side effects, such as fever and fatigue. They alerted British medical regulators.

On June 5, the researchers amended the trial protocol at the request of regulators to add a new group that would receive the correct full dose of the vaccine. Three days later, they alerted trial subjects to what they called “recent changes in the study” in a two-page letter attached to an updated 13-page “Participant Information Sheet.”

The letter, signed by chief investigator Pollard, stated that researchers “are not sure what dose of vaccine is most likely to be protective against COVID disease” and explained that doses “are measured using standard scientific test methods.” It said the late-stage trial participants received a dose measured using one method and that another group will receive a dose measured using a different test to match the dose given in another clinical trial of the vaccine.

It said the lower dose is “still in the normal range of doses that are used in clinical trials” and “if it can provide protection, it might be better for use in vaccine programmes.”

Caplan said the explanation would be of “no interest whatsoever to the subject because it’s too technical. To me, that qualifies as gobbledygook. What you want to know is, why are they doing this, we made an error, it involved dosing, we’re not worried about it.”

He and other ethicists interviewed by Reuters said researchers are obligated to be forthcoming with test subjects when things go wrong.

“As a letter purporting to explain a) an error and b) a change of protocol I find this entirely inadequate,” said Simon Woods, a professor of bioethics at Newcastle University, in an email. “It reads like a routine update (and a complex one at that).”

Emma Cave, a professor of healthcare law at Durham University’s law school, said: “Presenting the dosing variation as a planned change in the study is potentially a breach of trust if in fact the dosing resulted from an error. The letter makes clear the dosing change but not the reason for the change.”

To read the earlier Reuters report on the dosing error, click: here

https://www.reuters.com/article/us-health-coronavirus-vaccine-oxford-exc/exclusive-oxford-kept-covid-19-vaccine-trial-volunteers-in-dark-about-dosing-error-letter-shows-idUSKBN2A1263

Horizon Therapeutics ups rare-disease portfolio with $3B Viela buy

 Horizon Therapeutics plc has agreed to buy Viela Bio Inc for about $3.05 billion as it looks to boost its rare-disease portfolio, the drugmakers said on Monday.

Horizon will acquire all of Viela’s common stock for $53 per share in cash and expects the deal to close in the first quarter of 2021.

“This acquisition represents a significant step forward in advancing our strategy – to expand our pipeline in order to accelerate our growth over the long term,” Horizon Chief Executive Officer Tim Walbert said.

Viela’s only approved drug, Uplizna, is used to treat a rare, severe, neuroinflammatory disease named neuromyelitis optica spectrum disorder that attacks the optic nerve spinal cord and brain stem.

Horizon, which had $2.08 billion in cash and cash equivalents as of Dec. 31, expects the transaction to reduce its adjusted EBITDA by about $140 million in 2021.

https://www.reuters.com/article/us-viela-bio-m-a-horizon-therapeu/horizon-therapeutics-boosts-rare-disease-portfolio-with-3-05-billion-viela-bio-buy-idUSKBN2A12EW

Matinas Topline Results of LYPDISO™ Against Vascepa Positive

 – LYPDISO demonstrated a statistically significant 46% relative percent increase in EPA change from baseline over Vascepa® –

– LYPDISO demonstrated a 39% relative difference in response over Vascepa in TG reduction –

– Primary endpoint of percent change from baseline to end of treatment in triglycerides in the pharmacodynamic population did not meet statistical significance over Vascepa® –

– Per protocol analysis demonstrated statistical significance and superiority vs. Vascepa® on several key lipid and inflammatory markers –

– Management to host conference call today, Monday, February 1, 2021 at 8:00 a.m. ET –

The conference call can be accessed by dialing 877-407-5976 for participants in the U.S. or Canada and 412-902-0031 for international callers (reference passcode 13715418).

The conference call will also be webcast live on Matinas' website, www.matinasbiopharma.com, under the ‘Investors’ section and will be archived there for 90 days.

https://www.globenewswire.com/news-release/2021/02/01/2167088/0/en/Matinas-BioPharma-Announces-Topline-Results-from-ENHANCE-IT-Study-of-LYPDISO-Against-Vascepa.html

Gilead partners with cancer biotech Gritstone on HIV immunotherapy

 

  • Gilead will partner with a small Californian biotech to develop an immunotherapy for HIV, announcing Monday a collaboration-and-option deal with the company, Gritstone Oncology, that could be worth hundreds of millions of dollars.
  • Per deal terms, Gilead will pay Gritstone $30 million upfront and invest another $30 million in the smaller company's stock. Gritstone could receive as much as $725 million more, should Gilead exercise an option to take the treatment forward following early clinical tests, and if other, unspecified milestones are met. All or some of that money may never materialize, however, if development doesn't go as planned.
  • Gilead and Gritstone envision the immunotherapy working much like a vaccine to teach the immune system which targets to attack and destroy, except they plan for it to be used as treatment rather than for prevention.

Gritstone, as its full name suggests, was started as a cancer drug developer. Since launching a little more than five years ago, the biotech's chief focus has been advancing research into personalized and donor-based cancer immunotherapy.

Lately, though, Gritstone is making headlines for its efforts in infectious disease. Two weeks ago, the company announced plans to develop a coronavirus vaccine together with the U.S. National Institutes of Health and the Bill and Melinda Gates Foundation. Borrowing from its cancer work, Gritstone believes it can design a vaccine capable of eliciting a stronger response from virus-killing T cells than current candidates and will soon start a Phase 1 clinical trial.

Shares in Gritstone more than tripled following the coronavirus vaccine announcement.

Monday's deal with Gilead calls more attention to the infectious disease applications of Gritstone's cancer research.

Some of the preclinical testing underpinning Gritstone's immunotherapies used model proteins derived from simian immunodeficiency virus, the monkey version of HIV. These proteins functioned as stand-ins for the cancer proteins Gritstone aims to teach the body to target with immunotherapy.  

The T cell response in monkeys treated by Gritstone "captured the attention of Gilead's virology team," said Karin Jooss, head of research and development at Gritstone, in a Feb. 1 statement.

Gilead sells more than half a dozen HIV therapies, which combined earn the company billions of dollars each year. But while all are potent drugs, capable of keeping the deadly virus in check, none are curative and must be taken chronically.

Like other companies in HIV research, Gilead has worked to develop longer- and longer-lasting treatments, including an experimental drug called lenacapavir now in late-stage testing. The biotech also has four drugs in earlier stages that are designed to be steps toward the broader goal of an HIV cure.

Gilead and Gritstone have similarly high hopes for the vaccine-based approach they plan to take under Monday's collaboration deal. Gilead will use Gritstone's vaccine-like technology, which combines an adenovirus vector with self-amplifying messenger RNA, to target HIV-specific "antigens," or target proteins, that it's developing. The idea, according to Gilead and Gritstone, is to train the immune system to destroy HIV-infected cells.

The idea of a "T cell vaccine" for HIV is not new, however, and past efforts using different approaches have come up short, too.

Gilead will be responsible for a Phase 1 study of the therapeutic vaccine, after which it has the choice to obtain an exclusive license for further development.

https://www.biopharmadive.com/news/gilead-gritstone-hiv-vaccine-immunotherapy/594258/

Dynavax Gets $99M Funding for Covid Response Adjuvant Manufacturing

  Dynavax Technologies Corporation (Nasdaq: DVAX), a biopharmaceutical company focused on developing and commercializing novel vaccines, and the Coalition for Epidemic Preparedness Innovations (CEPI) today announced they have entered into an agreement to support the supply of Dynavax's CpG 1018 advanced adjuvant to be used in approved COVID-19 vaccines developed by CEPI grantees.

Under the terms of the agreement, CEPI will provide Dynavax funding of up to $99 million through a forgivable loan for the manufacturing of CpG 1018 with the potential to support hundreds of million doses of COVID-19 vaccine for delivery in 2021 through COVAX. COVAX is the global initiative to ensure rapid and equitable access to COVID-19 vaccines for all countries, regardless of income level. This stockpile of CpG 1018 will be first available for purchase by CEPI grantees for use in approved COVID-19 vaccines. Dynavax will sell the reserved CpG 1018 under separate commercial supply agreements made directly with CEPI grantees within price parameters agreed with CEPI. Upon sale of CpG 1018 manufactured under this agreement, Dynavax will reimburse CEPI for the funded manufacturing cost. If the relevant vaccine programs are unsuccessful and no alternative use is found for the adjuvant, the loan will be forgiven.

https://finance.yahoo.com/news/dynavax-cepi-announce-99-million-120100542.html