Another step backwards for Valneva

 Valneva has had a tricky time developing its Covid vaccine VLA2001, with the UK rejecting the jab and the EU insisting on more data. Yesterday the EMA put the boot in once more, stating that authorisation of VLA2001 would be delayed, and was unlikely to occur before mid-April. 

The vaccine under development by Sanofi and Glaxosmithkline, now known as Vidprevtyn, is also a casualty of delays at the EMA. But better news came for Novavax in the shape of UK authorisation for its Nuvaxovid jab – underlining the disappointment for Valneva, whose jab the UK rejected. 

When asked why the rolling review of the Valneva vaccine would take more time than expected, an EMA spokesperson appeared to suggest that the ball was in the developer’s court. 

Marco Cavaleri, the organisation’s head of vaccines strategy, said during a press briefing yesterday that the EMA needed to look at in-depth clinical data on VLA2001, saying it was “difficult for us to see that we will be in the position to conclude before Eastertime”. 

Mr Cavaleri’s statements about the Sanofi/Glaxo shot were along similar lines, namely that the agency would need full clinical results on Vidprevtyn before it could make a decision. In its fourth-quarter results presentation today Sanofi said the safety and efficacy trial of its primary Covid vaccine was due to be reported towards the end of the first quarter. 

Super Nova

Meanwhile Novavax’s Nuvaxovid, which in December became the fifth EU-approved vaccine, yesterday became the fifth in the UK. Like Valneva’s shot, this product has had a tricky time of it; its pivotal trial readout was a long time coming, and then last summer Novavax admitted that its application for US emergency authorisation would be delayed by three months.

In the event the timelines were even worse: the US application was only made this week.

UK approval is something, at least. The country has ordered up to 60 million doses of Nuvaxovid, which has shown respectable efficacy and acceptable cross-reactivity against Omicron.

Analysts from Jefferies, writing in November, forecast a punchy $5bn for the jab, and to be fair the World Health Organisation’s Covax initiative has ordered more than a billion doses.

In terms of sales expectations for the coming year Valneva’s candidate is languishing at the bottom of the pile. The group guided to worldwide revenues of €350-500m ($400-572m) for VLA2001 in 2022, and that was before the EMA’s announcement.

Selected vaccines in the EU
Company	Vaccine	Type	Date authorised in EU	WW sales 2022e ($bn)
Pfizer/Biontech	Comirnaty	mRNA	Dec 21, 2020	33.6
Moderna	Spikevax	mRNA	Jan 6, 2021	20.3
Astrazeneca	Vaxzevria	Chimp adenovirus vaccine	Jan 29, 2021	1.3
Johnson & Johnson	Ad26.COV2.S/ JNJ-78436735	Adenovirus	Mar 11, 2021	3.0
Novavax	Nuvaxovid	Recombinant spike protein	Dec 20, 2021	5.0
Sanofi/ Glaxosmithkline	Vidprevtyn/ SP0253	Recombinant spike protein	Review began Jul 20, 2021	1.5
Valneva	VLA2001	Inactivated virus	Review began Dec 2, 2021	0.49
Gamaleya Institute	Sputnik V	Adenovirus	Review began Mar 4, 2021	-
Sinovac Life Sciences	Vero Cell Inactivated	Inactivated virus	Review began May 4, 2021	-
Curevac	CVnCoV	mRNA	Application withdrawn Oct 11, 2021	-
Source: Evaluate Pharma, company statements and sellside analysts. https://www.evaluate.com/vantage/articles/news/policy-and-regulation/another-step-backwards-valneva

Transcript : Twist Bioscience Corporation, Q1 2022 Earnings Call, Feb 04, 2022

https://www.marketscreener.com/quote/stock/TWIST-BIOSCIENCE-CORPORAT-46874562/news/Transcript-Twist-Bioscience-Corporation-Q1-2022-Earnings-Call-Feb-04-2022-37749344/

Transcript : Bristol-Myers Squibb Company, Q4 2021 Earnings Call, Feb 04, 2022

 https://www.marketscreener.com/quote/stock/BRISTOL-MYERS-SQUIBB-COMP-11877/news/Transcript-Bristol-Myers-Squibb-Company-Q4-2021-Earnings-Call-Feb-04-2022-37749622/

Cytokinetics NDA for Omecamtiv Mecarbil Accepted By FDA

 Cytokinetics Inc. said the U.S. Food & Drug Administration has accepted and filed a new drug application for omecamtiv mecarbil, an investigational small molecule cardiac myosin activator, for the treatment of heart failure with reduced ejection fraction.

The company said the FDA assigned the NDA a standard review with a Prescription Drug User Fee Act target action date of Nov. 30, 2022. The FDA indicated it isn't planning to hold an advisory committee meeting to discuss the application.

The company said the NDA is supported by the results from a Phase 3 cardiovascular clinical trial of omecamtiv mecarbil that enrolled more than 8,000 patients in 35 countries across 945 sites. The trial demonstrated a statistically significant effect of treatment with omecamtiv mecarbil to reduce risk of the primary composite endpoint of cardiovascular death or heart failure events compared to placebo in patients treated with standard of care.

https://www.marketscreener.com/quote/stock/CYTOKINETICS-INCORPORATE-13479846/news/Cytokinetics-NDA-for-Omecamtiv-Mecarbil-Accepted-By-FDA-37748232/

Bayer Discontinues Clinical Development Candidate Eliapixant, Evotec Regains Rights

 Evotec SE (Frankfurt Stock Exchange, MDAX/TecDAX, ISIN: DE 000 566480 9, WKN 566480; NASDAQ) announces today that the Company has been informed by Bayer about a decision to discontinue the development of the investigational P2X3 receptor antagonist eliapixant (BAY1817080), which stems from a former Evotec/Bayer multi-target research alliance.

Following a review of the available data, Bayer concluded that the overall benefit no longer outweighs the risk in the actively pursued indications.

As a consequence of Bayer's decision, Evotec regains the rights to all P2X3 assets. The Company will evaluate the underlying data as soon as they are made available and will evaluate all options.

This decision has no impact on the overall strategic goals as outlined in Action Plan 2025.

https://finance.yahoo.com/news/bayer-discontinues-clinical-development-candidate-124500059.html

Vanda Phase 3 Study Misses Endpoints

 Vanda Pharmaceuticals Inc. (Vanda) (Nasdaq: VNDA) today announced results from its Phase III clinical study, VP-VLY-686-3303, evaluating the efficacy and safety of tradipitant in treating the symptoms of gastroparesis. The study did not meet its prespecified primary endpoint which was the difference between drug and placebo on the change of the severity of nausea from baseline at week 12 of treatment. Both treatment arms showed significant improvements from baseline on nausea as well as the other core symptoms of gastroparesis.

Initial exploratory analysis has identified potential confounders that may have masked the beneficial effect of the drug previously observed in the Phase II study of tradipitant, which include a baseline imbalance of rescue medication use between the two treatment arms as well as an observed poor compliance with study drug for some patients in the study. When restricting the analysis in the group of patients that used no rescue medications at baseline and adjusting for poor compliance, Vanda identified strong evidence of a drug effect across a number of symptoms and across the duration of the study, including a significant and meaningful effect at the prespecified primary endpoint of nausea change at week 12.

The Phase III study also continued to demonstrate that tradipitant is safe and well-tolerated, as seen in previous studies over the 12 weeks of treatment. Patients on tradipitant experienced a similar number of treatment emergent adverse events as patients receiving placebo. The most common adverse event where tradipitant frequency was higher than placebo was diarrhea. Patients that participated in the clinical program also had the opportunity to seek expanded access to tradipitant based on the benefit in the study and their individual unmet medical needs. Ten patients have received more than 3 months of tradipitant treatment, 6 of whom have received at least 1 year of tradipitant treatment.

https://finance.yahoo.com/news/vanda-pharmaceuticals-reports-results-phase-120000968.html

Israeli study offers strongest proof yet of vitamin D’s power to fight COVID

 Israel scientists say they have gathered the most convincing evidence to date that increased vitamin D levels can help COVID-19 patients reduce the risk of serious illness or death.

Researchers from Bar Ilan University and the Galilee Medical Center say that the vitamin has such a strong impact on disease severity that they can predict how people would fare if infected based on nothing more than their ages and vitamin D levels.

Lacking vitamin D significantly increases danger levels, they concluded in newly peer-reviewed research published Thursday in the journal PLOS One.

The study is based on research conducted during Israel’s first two waves of the virus, before vaccines were widely available, and doctors emphasized that vitamin supplements were not a substitute for vaccines, but rather a way to keep immunity levels from falling.

Vitamin D deficiency is endemic across the Middle East, including in Israel, where nearly four in five people are low on the vitamin, according to one study from 2011. By taking supplements before infection, though, the researchers in the new Israeli study found that patients could avoid the worst effects of the disease.

“We found it remarkable, and striking, to see the difference in the chances of becoming a severe patient when you are lacking in vitamin D compared to when you’re not,” said Dr. Amiel Dror, a Galilee Medical Center physician and Bar Ilan researcher who was part of the team behind the study.

He noted that his study was conducted pre-Omicron, but said that the coronavirus doesn’t change fundamentally enough between variants to negate vitamin D effectiveness.

“What we’re seeing when vitamin D helps people with COVID infections is a result of its effectiveness in bolstering the immune systems to deal with viral pathogens that attack the respiratory system,” he told The Times of Israel. “This is equally relevant for Omicron as it was for previous variants.”

Health authorities in Israel and several other countries have recommended vitamin D supplements in response to the coronavirus pandemic, though data on its effectiveness has been sparse until now.

In June, researchers published preliminary findings showing that 26 percent of coronavirus patients died if they were vitamin D deficient soon before hospitalization, compared to 3% who had normal levels of vitamin D.

They also determined that hospitalized patients who were vitamin D deficient were 14 times more likely, on average, to end up in severe or critical condition than others.

While the scientific community recognized the importance of the results, questions arose as to whether recent health conditions among the patients might have been skewing the results.

The possibility was raised that patients could have been suffering from conditions that both reduce vitamin D levels and increase vulnerability to serious illness from COVID-19, meaning the vitamin deficiency would be a symptom rather than a contributing factor in disease severity.

To zero out that possibility, Dror’s team delved deeper into the data, examining each of its patients’ vitamin D levels over the two-year stretch before coronavirus infection. They found that the strong correlation between sufficient vitamin D levels and ability to fight the coronavirus still held, and the level of increased danger in their preliminary findings remained almost identical.

“We checked a range of timeframes, and found that wherever you look over the two years before infection, the correlation between vitamin D and disease severity is extremely strong,” Dror said.

“Because this study gets such a good picture of patients’ vitamin D levels, by looking at a wide timeframe instead of just the time around hospitalization, it offers much stronger support than anything seen so far emphasizing the importance of boosting vitamin D levels during the pandemic,” he added.

A flood of dubious claims about natural remedies to the coronavirus, including a theory that Israelis had immunized themselves with lemons and baking soda, have left some skeptical about claims of vitamins warding off the virus.

But Dror insisted that his team’s research showed that the importance of vitamin D was not based on incomplete or flawed data.

“People should learn from this that studies pointing to the importance of taking vitamin D are very reliable, and aren’t based on skewed data,” he said. “And it emphasizes the value of everyone taking a vitamin D supplement during the pandemic, which, consumed in sensible amounts in accordance with official advice, doesn’t have any downside.”

https://www.timesofisrael.com/israeli-study-offers-strongest-proof-yet-of-vitamin-ds-power-to-fight-covid/