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Thursday, January 21, 2021

VBI Vaccines Progresses on Coronavirus Vaccine Program

VBI Vaccines Inc. (Nasdaq: VBIV) (VBI), a commercial-stage biopharmaceutical company developing next-generation infectious disease and immuno-oncology vaccines, today provided an update on the progress of its coronavirus vaccine program, consisting of two vaccine candidates: (1) VBI-2901, a trivalent pan-coronavirus vaccine candidate expressing the SARS-CoV-2 (COVID-19), SARS-CoV (SARS), and MERS-CoV (MERS) spike proteins; and (2) VBI-2902, a monovalent vaccine candidate expressing the SARS-CoV-2 spike protein.

"Over the last several months, the preclinical results achieved with our two coronavirus vaccine candidates continue to excite us, and we are working hard to get these candidates into the clinic in forms that are optimized both for clinical outcome and long-term commercial viability," said Jeff Baxter, VBI’s president and CEO. "The COVID-19 challenge we face as an industry is two-fold: first, how do we get the ongoing pandemic under control, and second, how do we ensure long-term protection against known and emerging coronaviruses. We continue to progress our candidates as we work to optimize, assess, and manufacture them, with the goal of bringing forward candidates that add meaningful clinical and medical benefit to those vaccines already approved – be it as a one-dose administration and/or providing broader protection against known and mutated future strains of COVID-19."

Phase 1/2 Human Clinical Study

VBI expects to initiate the first Phase 1/2 clinical study of VBI-2902 in Canada in Q1 2021. The clinical study protocol has previously been positively reviewed by Health Canada. Though there have been unanticipated delays in receipt of release testing materials due to recent industry-wide supply chain issues, the Company has been working closely with its partners and Health Canada to complete testing and release of clinical materials to enable clinical study initiation. This study will use clinical material manufactured by our manufacturing partner, National Resilience, Inc., formerly Therapure Biomanufacturing.

Work is ongoing to further optimize and manufacture the Company’s pan-coronavirus vaccine candidate, VBI-2901, with the anticipation that a Phase 1/2 study will begin later in 2021.

https://finance.yahoo.com/news/vbi-vaccines-announces-progress-coronavirus-130000486.html

Half of drugs rolled out since 2004 didn't live up to sales forecasts

 The Nasdaq Biotechnology Index has risen more than 600% in the last 15 years, reflecting investor enthusiasm for a flood of novel drugs that Wall Street analysts pegged as likely blockbusters.

But just how many of those drugs lived up to the Street’s high expectations?

Not nearly as many as investors—or biopharma companies—would hope. About half the drugs launched in the last 15 years underperformed analysts’ sales estimates by more than 20%, according to a recent report from L.E.K. Consulting. In fact, only one-fifth of new meds reached $1 billion in U.S. sales, and more than half failed to hit even $250 million.

Granted, the accuracy of analysts’ forecasts is likely to be “spotty,” L.E.K. said, because they put dollar estimates on products still in clinical development and therefore unproven. “However, even when looking at consensus forecasts just prior to launch—forecasts that are heavily informed by expected product labels and management expectations—40% of products underperform Street forecasts by more than 20%,” the firm wrote in an online summary.


L.E.K. found underperformers across many therapeutic areas, but a few stood out for producing the most duds. Half of new cardiovascular drugs fell short of expectations in their first three years, as did half of immunology meds. About 48% of new products to treat infectious diseases also failed to hit their marks.

No doubt the cardiovascular field has seen its fair share of high-profile—but ultimately disappointing—launches in recent years. Take PCSK9 inhibitors Repatha and Praluent, for example. The cholesterol-lowering drugs, from Amgen and Sanofi and Regeneron, respectively, were pegged as all-but-certain blockbusters when they hit the market in 2015, but neither has come close. Instead, they've been hampered by multiple factors, including massive price cutting.

Cancer drug launches performed slightly better than others, with only 38% failing to live up to the hopes pinned on them. Innovation helped. In fact, the oncology field produced 82 of the 450 new molecular entities L.E.K. tracked.


L.E.K.’s research uncovered another significant trend: Bigger companies are way better equipped than small biotechs are to successfully commercialize new products. The firm discovered that average peak sales for new products is 50% higher in Big Pharma than it is among smaller players.

Size and scale are often considered barriers to innovation, but when it comes to commercialization, “they become key enablers,” L.E.K. said.

Small companies launching drugs in the cardiovascular, infectious disease and immunology fields face particularly high hurdles, because they have to pitch those products to general practitioners as well as specialists. And small companies tend to underestimate “the challenge of educating and changing the prescribing behavior of a large and disparate group of physicians,” L.E.K. said.

The bottom line, the L.E.K. concluded, is that biopharma companies should rethink their strategies for providing pre-launch estimates to Wall Street analysts. “Since the negative impact of missing a forecast can be severe, particularly for a small biotech launching a first product,” the firm said, “companies must be cautious when providing revenue guidance and managing expectations from the Street.”

https://www.fiercepharma.com/pharma/half-drugs-launched-last-15-years-failed-to-meet-wall-street-s-expectations-report

Novo Nordisk, in Lilly's Trulicity steps, files higher Ozempic dose for diabetes

 Novo Nordisk and Eli Lilly are locked in a tough fight, both vying for the top spot in the GLP-1 diabetes treatment class. On strategy they’ve both pursued is increasing the dosing of their existing offerings to reach better efficacy. Now, Novo has made its regulatory move.

Wednesday, the Danish company said it had filed for U.S. approval of once-weekly Ozempic at a new dose of 2.0 mg. The GLP-1 analogue currently comes at two lower doses of 0.5 mg and 1.0 mg. It submitted the same label extension request to EU regulators in late December.

The news came after Lilly in September secured a U.S. nod for rival once-weekly GLP-1 drug Trulicity to include 3.0 mg and 4.5 mg doses on top of the original 1.5 mg offering.

Both drugs have shown they work better in diabetes patients when given at higher doses. For Ozempic specifically, in the phase 3b Sustain Forte trial, the 2.0-mg dose showed a statistically significant reduction in blood sugar levels compared with the 1.0-mg dose at week 40. More patients on the high dose achieved the American Diabetes Association treatment target of HbA1c—a commonly used metric for blood sugar—below 7%. The high-dose takers also lost more bodyweight than their low-dose counterparts did.


Ozempic’s been growing aggressively since its launch in 2018 as Lilly’s earlier-to-market Trulicity plays defense, even though the entire GLP-1 share in the diabetes market continues to increase thanks to the two drugs.

As of 2020’s third quarter, the two drugs were neck and neck in terms of U.S. new-to-brand share, with Ozempic at 34.7% and Trulicity 34.5%. Total scripts share was 44.3% for Trulicity, versus 26.8% for Ozempic.

But the focus at Novo Nordisk these days also includes newly launched Rybelsus, an oral drug that shares injectable Ozempic’s active ingredient, semaglutide. Approved by the FDA in September 2019, the drug is viewed as a market disrupter.

Merely 20 weeks into its launch, Rybelsus enjoyed new-to-brand share that matched that of the entire SGLT2 class, which also consists of oral medications. While its share slipped during the first few months of the COVID-19 pandemic, it has returned and been ticking upward as lockdowns lift. More good news for Novo: Over 80% of the drug's new scripts went to patients new to the GLP-1 class, CEO Lars Fruergaard Jørgensen said during a call in October.

During the third quarter of 2020, Novo also launched a phase 1 trial testing higher doses of oral semaglutide for diabetes.

Combined, Novo’s GLP-1 franchise, which also includes old stalwart Victoza, generated sales of DKK30.05 billion ($4.9 billion) during the first nine months of 2020, with Ozempic contributing half of that. By contrast, Lilly’s Trulicity hauled in sales of $2.9 billion during the same period after 22% year-over-year growth.


Novo’s ambitions for semaglutide lie beyond diabetes. Last month, the company filed a 2.4 mg, once-weekly version of the under-the-skin drug to the FDA as an obesity treatment after showing weight loss of around 15% to 18% across three phase 3 trials.

The drug also recently showed promise in non-alcoholic steatohepatitis (NASH) in a phase 2 trial, though industry watchers mostly expect it to be able to help earlier-stages patients but not those with heavier liver fibrosis. In a more surprising move, Novo unveiled in mid-December that it would launch a phase 3 trial of oral semaglutide in Alzheimer’s disease.

Lilly has its countermeasure taking shape, too. Its GIP and GLP-1 dual agonist tirzepatide just nailed a phase 3 trial in diabetes, showing significant improvements in blood sugar levels and body weight that were superior to placebo’s data. But both Lilly and Novo, as well as industry watchers, will be more interested in the readout from a second phase 3 trial dubbed Surpass-2, which pits tirzepatide against Ozempic.

https://www.fiercepharma.com/marketing/novo-nordisk-following-lilly-s-trulicity-footsteps-files-ozempic-higher-dose-for-diabetes

Antibody-assisted vaccination can speed path to Covid protection

 


After almost a year of pandemic terror, the end is in sight. But you still have to squint.

The FDA has granted emergency use authorization for two safe and effective vaccines that science has delivered at record speed. The question now is: How do we best distribute them?

The Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP) has published guidance that vaccinations should start with health care personnel and residents of long-term care facilities, followed by other essential frontline workers and those over 75 years old. Mentioned only as a subpriority is how a history of Covid-19 infection should affect one’s place in line: “HCP with documented acute SARS-CoV-2 infection in the preceding 90 days may choose to delay vaccination until near the end of the 90-day period in order to facilitate vaccination of those HCP who remain susceptible.”

Given the low risk for reinfection and the limited supply of vaccine doses, it would be a mistake not to make previous infection a more central consideration in our vaccine prioritization. With an estimated 75 million Americans having already been infected with SARS-CoV-2, but only 24 million knowing it, using wide-scale Covid-19 antibody testing can help better target vaccine allocation to those at highest risk. Doing so can save lives and return us to normalcy sooner.

This strategy builds upon the two biggest discoveries made in efforts against the virus. The first is that after infection, including mild and asymptomatic infections, there appears to be lasting and strong immunity out to six-plus months. The fact that there have been nearly 100 million cases of Covid-19 confirmed worldwide and only a handful of documented reinfections provides convincing evidence of lasting immunity. And even among the rare reinfections, their course will likely be milder thanks to the immune system’s memory.

The second breakthrough is the resounding success of Covid-19 vaccine development.

This combination of lasting immunity and effective vaccines has been the cornerstone of almost all past successes against viruses (HIV, to date, being the key exception). It’s how the scourges of smallpox, polio, measles, mumps, and other infectious diseases have been beaten. And it’s how we are going to beat Covid-19.

But even in a best-case scenario, it will be months before enough vaccine doses have been made to treat everyone. With epidemiologists estimating that two-thirds of the population must be immune for the herd protection needed to quell the pandemic, an antibody-assisted approach would let us reach that threshold faster.

Here’s another reason why an antibody-assisted approach to vaccination is needed: Due to the combination of inadequate testing and asymptomatic infection, most people infected with Covid-19 are never diagnosed with it. This is especially true in states hardest hit by the virus. In New York state, for example, it is estimated that 30% of the population has recovered from Covid-19 while only 7% have been diagnosed with the virus. Underdiagnosis isn’t limited to locales like New York, which had an early surge. More than 36% of North Dakotans are estimated to have been infected, while only 13% have been diagnosed. Given these discrepancies, in states like North Dakota, without the assistance of antibody testing, I estimate that as many as 1 in 4 vaccines could be given to someone who is currently immune to Covid-19.

While the presence of antibodies is not a perfect measure of immunity, thanks to both the rarity of reinfection and the accuracy of current antibody testing (with false positive rates around 1% or lower), those with antibodies can safely be considered a low-risk group. This reality was further confirmed in a recent New England Journal of Medicine report from Oxford University that followed 12,000 health care workers over six months and found no symptomatic infections in those with antibodies to SARS-CoV-2.

But theory and in practice are two different things. With the difficulty the U.S. has had scaling PCR testing, and with early vaccine distribution sputtering, efforts to test swaths of the public for antibodies may sound foolhardy. It isn’t.

In regards to scaling antibody testing, the process is wholly different from the PCR-based testing used to detect acute infection. Antibody tests are more like traditional bloodwork and are processed as automated immunoassays. This means they can be run in large batches on machines almost all functional medical laboratories already own and can use existing lab collection infrastructure for collection and processing. As Benjamin Mazer, a pathologist at Johns Hopkins Hospital, told me, “The delays we’ve faced with PCR testing shouldn’t deter people from antibody tests if they’re needed. The antibody test is far simpler to perform and can be turned around in hours instead of days.”

An easy place to start would be testing for antibodies in people already requiring lab tests for other reasons, such as when they are admitted to a hospital, at the emergency department, or have a clinic appointment. Standing orders paired with canceled copayments for others at clinical and commercial laboratories can further expand access. School- and employer-based batch testing can inform their future vaccination campaigns.

To be clear, it is both safe and beneficial for those previously infected with SARS-CoV-2 to be vaccinated (just like adults who had the chickenpox need a booster to prevent shingles). It is paramount proper investments be made to support both testing and vaccination. These efforts must be complements, not competitors. And if access to antibody testing is not readily accessible, vaccination should never be delayed. Lastly, once we have enough supply to meet public demand, everyone should be vaccinated, regardless of antibody status.

I could close with an argument about how an antibody-assisted approach would allow the U.S. to reach herd immunity faster. Or revive our economy quicker. Or protect more frontline workers — nurses, teachers, grocers, delivery drivers, firefighters, and others — sooner.

But for me, and I suspect for you too, it’s much less abstract than that. For every vaccine we save by using antibody testing, there will be one more we can give to a higher-risk individual anxiously awaiting her or his turn in line. And we all have loved ones standing in line: an elderly grandparent, an immunocompromised mom, or a cousin fighting cancer.

Given all we have done so far to keep them safe — deferred dining, canceled vacations, and missed hugs — we must employ every weapon in our armamentarium against this plague. This includes antibody testing.

Michael Rose is a resident physician in internal medicine and pediatrics at Johns Hopkins University School of Medicine.

https://www.statnews.com/2021/01/21/antibody-assisted-vaccination-will-speed-the-path-to-protection/

Lilly’s Blazes trail in Covid-19 prevention

 Antibodies, already authorised to treat mild to moderate Covid-19, could soon also be used to prevent the virus, a study of Lilly’s bamlanivimab in nursing homes suggests. To be eligible for the trial, called Blaze-2, nursing homes had to have had at least one confirmed coronavirus case. Across residents and staff receiving bamlanivimab, there was a 57% reduction in the risk of developing symptomatic Covid-19 compared with those receiving placebo. Among residents the figure was even more impressive, with an 80% reduction with bamlanivimab versus placebo. Lilly plans to speak to regulators about expanding bamlanivimab’s EUA; however, there are questions about the role of the antibody if the vaccine rollout goes well. The logistics of infusing nursing home residents on a large scale might be also be tricky. Other antibody developers are looking at prevention, and a notable player here is Astrazeneca with AZD7442, a long-acting antibody. This is given intramuscularly, which could give it an edge over bamlanivimab and Regeneron’s casirivimab/imdevimab, which are both intravenous. Glaxosmithkline also has a long-acting project, the intravenous VIR-7831, but that does not appear to be in any prevention studies; the pivotal Comet-Ice trial in outpatients is set to read out this quarter.

Selected prevention studies with Covid-19 antibodies
ProjectCompanyTrialSettingData?
Bamlanivimab (LY-CoV555)*LillyBlaze-2**(NCT04497987)Prevention in nursing home residents and staffPositive data reported
Casirivimab + imdevimab (REGN-COV2)***RegeneronStudy 2069 (NCT04452318)Prevention in household contacts of Covid-19 patientsDue H1 2021
AZD7442AstrazenecaProvent (NCT04625725)"Pre-exposure prophylaxis"Due H1 2021
Storm Chaser (NCT04625972)"Post-exposure prophylaxis"
*Trial also includes combo with LY-CoV016 in treatment; **Conducted with NIAID; ***Subcutaneous formulation. Source: clinicaltrials.gov & EvaluatePharma.

https://www.evaluate.com/vantage/articles/news/snippets/lillys-blazes-trail-covid-19-prevention

XBiotech: Covid antibody therapy works on variant

 XBiotech Inc. (XBIT) reported that its COVID-19 candidate True Human antibody therapy may also be used for treating the COVID-19 mutant virus that recently emerged in the UK and is now rapidly spreading across the US.

https://www.nasdaq.com/articles/stock-alert%3A-xbiotech-up-6-2021-01-21

Aditxt Covid Immune Monitoring Service to be Operational February 1

 Aditx Therapeutics, Inc. (Aditxt) (the “Company”) (Nasdaq: ADTX), a life sciences company developing biotechnologies specifically focused on improving the health of the immune system through immune monitoring and reprogramming, today announced the operational launch of the AditxtScore™ Immune Monitoring Platform as of February 1st, 2021.

The initial application of the platform will be AditxtScore™ for COVID-19 which has been designed to provide a more complete assessment of an individual’s infection and immunity status with respect to the SARS-CoV-2 virus. Infection status will be determined by evaluating the presence or absence of the virus, and immunity status by measuring levels of antibodies against viral antigens and their ability to neutralize the virus. Aditxt will soon be expanding the panel to measure other components of the immune response such as cellular immunity.

AditxtScore™ for COVID-19 will be available as a Lab Developed Test (LDT) and processed at the AditxtScore™ Immune Monitoring Center, which will operate as a CLIA-certified reference lab for the Company’s prospective channel partners, including labs and hospitals.

https://finance.yahoo.com/news/aditxtscore-immune-monitoring-operational-february-130000310.html