Oncocyte: New Data on Pan-Cancer Utility of DetermaIO at AACR

 Achieved primary endpoint demonstrating significant correlation between DetermaIO and two-year overall survival rate to atezolizumab in metastatic bladder cancer

DetermaIO identified additional immunotherapy responsive patients missed by commonly used biomarkers

Data supports potential utility of DetermaIO test across multiple solid tumors as predictor of response to Immune Checkpoint Inhibitor therapy in estimated $3 billion market in the United States

KOL Webinar discussing results to be held on April 19 at 11:30 AM EDT/8:30 AM PDT

https://finance.yahoo.com/news/oncocyte-presents-data-2021-american-173100664.html

AACR: Bayer Aliqopa leaps ahead of Gilead Zydelig in lymphoma

The PI3K inhibitors were once viewed as a blockbuster opportunity in blood cancer. But patient deaths in clinical trials for earlier-line use of Gilead Sciences’ first-to-market Zydelig dashed that hope. Now, in what could be viewed as a redemption of the drug class, Bayer’s Aliqopa has come up with a success safely.

Adding Aliqopa to Roche’s Rituxan cut the risk of disease progression or death by 48% in patients with indolent non-Hodgkin’s lymphoma (iNHL) who relapsed after at least one prior therapy, according to data presented at the virtual American Association for Cancer Research annual meeting.

This showing makes Aliqopa the first PI3K inhibitor to demonstrate superior efficacy in combination with Rituxan with a manageable safety profile in patients with relapsed iNHL, Scott Fields, Bayer’s head of oncology development, said in a statement.

Bayer now plans to file the data to FDA and other drug regulators to potentially get Aliqopa into earlier, second-line iNHL, Barry Childs, Bayer’s global development lead for Aliqopa, said in an interview. The drug currently bears an accelerated approval in third-line follicular lymphoma (FL) based on tumor response data.

It also hopes the data, from the phase 3 Chronos-3 trial, could turn that conditional nod into a full one. The confirmatory trial Bayer has previously agreed with the FDA is actually the Chronos-4 study, which is testing Aliqopa in tandem with Rituxan and chemotherapy in relapsed iNHL. But Childs said the company will ask the FDA to consider using the current study instead, given that it’s also a randomized trial.

For a second-line filing, Bayer intends to aim for a broader label for the whole iNHL population, though the FDA might pick apart each subset of disease, Childs and Fields cautioned during the interview.

Aliqopa’s benefits were shared across all prespecified iNHL subtypes in Chronos-3. For FL, the risk reduction amounted to 42%. The number was 52.5% for marginal zone lymphoma (MZL), 75.7% for small lymphocytic lymphoma (SLL) and 55.7% for Waldenstrom macroglobulinemia.

For the larger FL and MZL diseases, the subgroup analyses are powered to stand on their own, while the two smaller diseases aren’t statistically powered, according to Childs. That said, “there is consistent treatment effect,” he added. “What we’re requesting of the FDA is that they will consider the treatment effect consistency to be part of their approval decision for the smaller subsets.”

As for the perhaps more important data on Aliqopa’s ability to extend patient’s lives, Childs said the overall survival data were still immature after a median follow-up of 30 months as neither treatment arms has reached a median survival mark.

Gilead’s PI3K inhibitor Zydelig entered the U.S. market in 2014 for previously treated chronic lymphocytic leukemia, FL and SLL, bearing blockbuster hopes. However, the company was forced to cap several trials—including ones equivalent to Aliqopa’s Chronos-3 and Chronos-4—after reports of multiple deaths in its clinical programs in 2016. After that, the drug’s sales have never picked up, with just $72 million in 2020.

In Chronos-3, the Aliqopa regimen showed side effects that were generally consistent with the individual drugs, according to Bayer. Some of the frequent side effects such as hyperglycemia were transient and manageable, the company said.

There was however a relatively high discontinuation rate of 32% in the Aliqopa arm, versus 8% for solo Rituxan. The company is still exploring the exact reason, but Childs pointed to a higher rate of complete tumor clearance among Aliqopa patients, suggesting that some investigators may have chosen to discontinue patients especially during the pandemic because they were already in good remission. He also noted that the company took a very conservative protocol to discontinue patients who developed pneumonitis but only later realized that the side effect can be managed without taking patients off treatment.

In terms of managing side effects, Childs pointed to Aliqopa’s intravenous administration—versus Zydelig and other PI3K inhibitors’ oral dosing—as an advantage as it can be given intermittently to allow normal tissues to recover between doses.

So far, Aliqopa still hasn’t earned a place in Bayer’s annual report, meaning that its 2020 sales were below the €262 million ($312 million) prostate cancer drug Xofigo raked in during the period. Verastem Oncology recently transferred its PI3K drug Copiktra to Secura Bio for $70 million upfront. That drug sold merely $9.3 million in the first half of 2020. TG Therapeutics just got a go-ahead for Ukoniq, and Incyte’s waiting in the wings with parsaclisib.

But as Bayer pharma chief Stefan Oelrich laid out at a recent investor event, the German company expects to see about €500 million in Aliqopa peak sales. With the Choronos-3 win, Bayer may now seek to move Aliqopa into earlier line of treatment and to markets beyond the U.S., Fields said.

https://www.fiercepharma.com/marketing/aacr-redemption-pi3k-drug-class-bayer-s-aliqopa-leaps-ahead-gilead-s-zydelig-lymphoma

N.H. To Allow Vaccines For Non-Residents Starting April 19

 New Hampshire will soon loosen its residency restriction for COVID-19 vaccine eligibility even further, allowing Massachusetts residents to cross state lines for an appointment.

Gov. Chris Sununu says starting April 19, non-residents, no matter where they live, can register for a COVID-19 vaccine in New Hampshire. They’ll have to sign up, like everyone else, through the state-run vaccination site, vaccines.nh.gov.

“Whether you live in Boston, Maine, Vermont, New York, doesn’t matter, come on in, get your vaccine. We’re open for business,” Sununu said at a press conference Thursday in Concord.

Last Friday, the state opened up vaccine eligibility to all New Hampshire residents 16 and older, but, at the time, did not include people like out-of-state college students or second-home owners.

Sununu said Thursday the increased availability of COVID vaccines led him to reverse course.

After the state opened eligibility to residents 16 and older, over 100,000 people have registered for the vaccine. The state says new registrations are coming in at an average of 5,000 to 6,000 per day.

Sununu said the number of Granite Staters signing up for vaccines is now slowing down, and there are over 200,000 appointments available between now and Memorial Day.

So far, around 60% of eligible residents have either already been vaccinated or have an appointment booked, according to state health officials.

As vaccinations increase, Sununu has been pushing for other aspects of life in New Hampshire to return to some version of normal. Last week, he announced that all schools in the state must return to full in-class instruction by April 19.

A number of schools are pushing back and asking for an extension, but Sununu has remained firm on his mandate.

“Most schools in the state have been up and running without being fully vaccinated or even vaccinated at all,” Sununu said Thursday.

If a school continues to not offer the full in-person learning past the April 19 deadline, Sununu said those days would not count toward state-mandated instructional hours, and that time may need to be made up by schools later in the year.

Sununu said the state is not “allowing hybrid and remote learning anymore unless it's requested by the individual, the student themselves.”

Even as vaccination becomes widespread, new COVID cases continue on an upward trend across New Hampshire.

State health officials announced 515 new cases of COVID-19 Thursday. That's the highest one-day number of new cases in more than two months.

The number of hospitalizations in the state due to COVID-19 topped 100, continuing a steady, daily increase in that number.

Officials reported one new death from COVID-19.

https://www.wbur.org/commonhealth/2021/04/09/new-hampshire-vaccines-residency-requirement-dropped

Chinese mRNA vaccines seen ready to hit market by end of year

China is on course to produce its own version of the revolutionary new vaccines that use genetic technology to stimulate the immune system by the end of the year, according to a senior industry figure.

The two available mRNA vaccines designed to tackle Covid-19 – produced by Moderna and Pfizer-BioNTech – have a higher efficacy rate than those produced using other forms of technology.

“We fully expect that there is a high possibility that a domestic mRNA vaccine will hit the market by this year,” said Feng Duojia, president of the China Association of Vaccines.

“We increasingly feel that we must master the core theories and technologies … because no one can help our country solve all the immunisation problems once a global public health crisis like Covid-19 breaks out. We must have a long-term strategy,” he added.

A senior executive with Walvax, who declined to be named because he was not authorised to speak to the media, said there would be uncertainties concerning regulatory approval for product launch. 

Feng said an mRNA vaccine jointly developed by the Academy of Military Science (AMS), Walvax Biotechnology and Suzhou Abogen Biosciences, has completed its phase 1 and 2 human trials with “satisfactory” results. He continued that plans for phase 3 trials in multiple sites overseas were under way and expectations were “very good”.

Walvax started building a production facility in December with a first-phase annual capacity of 120 million doses.

Another mRNA vaccine jointly developed by Shanghai-based biotechnology company Stemirna Therapeutics and Shanghai East Hospital, started human trials last month, two months after it obtained regulatory approval to do so.

Meanwhile, Fosun Pharmaceutical, which has a licensing deal with BioNTech in the Greater China area, is still sorting through data from phase 2 trials held in Jiangsu province. It has already started delivering batches of the 

Covid-19 vaccine

 to Hong Kong and Macau.

Fosun is co-developing the vaccine by having early stage trials on the mainland before using phase 3 data from overseas to seek mainland China’s regulatory approval.

“The preparations at the production facility are ready … After effective results are obtained through these trials, an application will be submitted to the relevant government agency immediately, with the hope to start domestic production of the foreign vaccine in China,” Feng said.

Feng said the developers are “racing against time without relaxing for a moment” and the production facilities were being prepared before the trial results were known in a break with the usual practice of waiting until the drug’s effectiveness has been proven.

“We are latecomers and will still have some time before the products are approved, but these products feature Chinese innovation and intelligence with independent intellectual property rights and patents for the core parts of the production process and core technology. We do not have to worry about technical bottlenecks and obstacles in the future,” Feng said.

The Chinese vaccines currently in use are inactivated vaccines, which take dead matter from the coronavirus to stimulate the immune system. But the radical new vaccines use messenger RNA to copy the virus’s genetic profile and train the body into mounting an immune response.

The technology has a number of advantages, including a shorter development time if changes are needed to combat viral variants and better biosafety because there is no need to handle live viruses as part of the production process.

That synthetic mRNA is wrapped in an oily coating made of lipid nanoparticles (LNP), which helps deliver the vaccine and is considered the key technology for unlocking its potential.

Only a handful of companies supply LNP, including Germany’s Merck and Evonik, Switzerland’s Corden Pharma and Canada’s Acuitas. Walvax has developed its own LNP for the vaccine and Stemirna said it has developed its own nano delivery system using lipopolyplex.

According to a paper published in Cell, the Walvx-Abogen-AMS candidate vaccine can be kept at room temperature for up to a week, whereas the Pfizer-BioNTech product needs to be stored well below zero and the Modena vaccine can be kept in a fridge for up to a month, but needs ultra-low temperatures for longer term storage.

Jay Lee, an analyst for the investment company Morningstar, said mRNA platforms are in the early stages of development, but potentially have broad applicability in other areas beyond Covid-19, such as infectious diseases and cancer. He believes Chinese companies will eventually be competing with global players in developing the technology.

“In the long-run, many Chinese biotech companies want to compete in the global markets, especially the US market which offers far more lucrative pricing compared to most other countries, including China. This requires early investment in new drug targets and modalities, including mRNA platforms which could ultimately prove to have broad applicability beyond Covid-19,” Lee said.

https://www.scmp.com/news/china/politics/article/3128998/revolutionary-mrna-vaccines-made-chinese-firms-will-be-ready

China Knocks on People's Doors to Speed Up Domestic Covid-19 Vax

 A year after Covid-19 swept through China, the virus is under control. Now authorities have to motivate a population that feels little urgency to get vaccinated by using a mix of social pressure, incentives, education and coercion.

While surveys show vaccine acceptance remains high, the motivation to go out and get inoculated is lagging in the world's second-largest economy given low infection rates.

China's public health officials say the aim is to get 40% of the population vaccinated by summer. With the country administering more than 4.5 million shots a day in the past week, 161 million had been given by the end of Friday, according to the National Health Commission. Oxford University data-tracking project Our World in Data said about 11% of China's population had received at least one dose.

That is a long way from herd immunity -- which would require about 80% coverage -- and compares with about a third of the U.S., according to the U.S. Centers for Disease Control and Prevention.

Another challenge for China is the low efficacy rate of its vaccines currently in use. Preliminary data suggest that they range somewhere between 50% to 80%. To optimize the protection rate, China was looking into, for example, adjusting the dosage, adding an extra shot or changing the interval between injections, George Gao, director of China's Center for Disease Control and Prevention, said Saturday.

A senior Chinese official said last month that vaccine coverage is fundamental to the recovery of the world's second-largest economy, during an teleconference call with local officials to accelerate the country's vaccination drive. One of the country's most highly regarded public health experts has tied success to patriotism and national security.

With motivation low, China's neighborhood committees, companies and schools have been deputized to bring vaccines to people rather than wait for them to sign up. Community workers and residential-compound managers are calling people and knocking on doors, showing older people how to book slots on their mobile phones, handing out fact sheets, setting up information stalls and answering questions from those who remain hesitant. A dozen people said they had been asked multiple times by their building management or workplace to sign up for a vaccine.

In the capital, Beijing, shops, restaurants and markets can put up a green certificate at their entrance if 80% of their employees have been inoculated. Bright red banners on streets and catchy jingles on social-media platforms remind people to get the shots.

The city had administered at least one dose to half its 21.5 million residents by early April, and a local health official said last week that it aims to cover its adult population by the end of May.

Si Weijiang, partner at the Shanghai-based DeBund Law Offices, booked his slot after his workplace circulated a sign-up sheet through all-purpose mobile messaging app WeChat, and he received his first shot March 25 in a gymnasium turned vaccination site.

"I regard getting vaccinated as my social duty," he said, adding that his qualms about the vaccines' safety were assuaged after seeing some of his colleagues and friends get inoculated.

China's domestic vaccination had already started off slowly this year. With vaccine makers constrained by production capacity and focused on exporting doses, it fell short of reaching an internal target reported by The Wall Street Journal to fully inoculate 50 million people before Lunar New Year in mid-February. Other Asia-Pacific countries that succeeded in controlling the spread of the coronavirus have also lagged behind much of the West in inoculations.

A few months ago, Chinese public-health experts picked up on a lack of urgency to get vaccinated. A nationwide survey by researchers from Peking University, China's CDC and the National Health Commission collected data that found vaccine acceptance between March and December last year was around 90% among more than 2,000 respondents. But the proportion of those who wanted to get inoculated as quickly as possible fell to 23% from 58% between the height of China's outbreak and when it had brought the virus under control.

The predominant reasons for hesitance, this and another study of healthcare workers in the eastern province of Zhejiang found, were inconvenience, safety concerns and a feeling that the risk of infection was low.

None of the five vaccines approved in China have been included in the World Health Organization's emergency-use list, and Chinese vaccine-makers haven't publicly released detailed efficacy data. In recent years, scandals involving ineffective, fake or substandard vaccines have damaged the image of Chinese vaccine makers and vendors. Still, nearly half of the respondents in the nationwide survey said they preferred domestic vaccines over imported ones.

"There are so many reasons, or excuses, for me to wait and see," said Simon Zhang, a marketing manager for an Italian company who moved from Italy to his hometown of Zhengzhou in central Henan province in February. He pointed to worries about the vaccine's effectiveness against future variants and the potential short duration of its protection.

Another concern is that China can't maintain forever the strict border controls that have helped it contain infections, said Zhong Nanshan, an epidemiologist who leads China's National Health Commission's Covid-19 expert group, in a recent interview with domestic media.

"If China completely opened to the world now, that would be very dangerous because most people don't have immunity," he said.

As of late March, China had set up more than 27,000 vaccination sites, a Chinese CDC official said. The centers are open into the evening, and teams have been deployed to universities, police stations and housing compounds to provide door-to-door service. Some local governments have doled out incentives such as shopping coupons worth about $7.50, or free ice cream and eggs.

Some at times have threatened punitive measures: Last week, officials in Wancheng town in the southern island province of Hainan province apologized for threatening to bar people from public transport if they refused to get vaccinated, according to the Communist Party-run tabloid Global Times.

In around four border towns in the southwest, shots were briefly compulsory. After Ruili, on the Myanmar border, locked down because of a cluster in late March, local authorities launched a five-day blitz on April 2 to vaccinate 300,000 people. On Tuesday, local authorities suspended the campaign to focus on testing the population for a second time instead, local officials told The Wall Street Journal.

Production bottlenecks in some areas could continue to hamper quicker progress. Several cities extended the time frame for a second dose. Haikou, Hainan's capital, suspended them last week except for people working at the annual Boao Forum policy gathering.

And glass vials used for vaccine packaging are still in short supply, wrote Cui Ernan, an analyst at consulting firm Gavekal Dragonomics: "Solving this issue and achieving herd immunity within the year is still improbable, but not impossible."

https://www.marketscreener.com/news/latest/China-Knocks-on-People-s-Doors-to-Speed-Up-Domestic-Covid-19-Vaccination--32929926/

French vaccine biotech Valneva files for a $100 million US IPO

Valneva, a commercial-stage French biotech developing vaccines for infectious diseases, filed on Friday with the SEC to raise up to $100 million in an initial public offering. The company is currently listed on the Euronext Paris (VLA).

Valneva has successfully licensed and commercialized a portfolio of traveler vaccines, composed of IXIARO (also marketed as JESPECT in Australia and New Zealand) for the prevention of Japanese encephalitis in travelers and military personnel and DUKORAL for the prevention of cholera. Its clinical portfolio contains lead program VLA15, a vaccine targeting Borrelia (Lyme disease) under development in collaboration with Pfizer, which is currently in Phase 2 trials.

The Saint-Herblain, France-based company was founded in 1999 and booked $131 million in sales for the 12 months ended December 31, 2020. It plans to list on the Nasdaq under the symbol VALN. Valneva filed confidentially on January 15, 2021. Goldman Sachs, Jefferies, Guggenheim Securities and Bryan, Garnier & Co are the joint bookrunners on the deal. No pricing terms were disclosed.

Relevant Profile: VALN

https://www.renaissancecapital.com/IPO-Center/News/80620/French-vaccine-biotech-Valneva-files-for-a-$100-million-US-IPO

Studies Fail to Show Long-Term Benefit for CPAP

 Sleep medicine specialists are worried about a draft technology assessment from the Agency for Healthcare Research and Quality (AHRQ) that casts doubt on the long-term clinical benefit for the gold standard treatment for sleep apnea.

Reviewers found that studies of continuous positive airway pressure (CPAP) have consistently failed to show improvements in non-sleep-related outcomes linked to obstructive sleep apnea (OSA), such as stroke, heart attack, diabetes, and depression.

The report -- online at the AHRQ website and open for public comment through April 23 -- concluded that the published evidence "mostly does not support that CPAP prescription affects long-term, clinically important outcomes," and it highlighted research gaps and methodological weaknesses in the available studies, along with significant CPAP compliance issues, which have all contributed to the failure to show long-term benefits for the treatment.

OSA specialists who spoke to MedPage Today about AHRQ's research review agreed that CPAP remains by far the most effective treatment for sleep-related symptoms of OSA. They worried that the report could be misinterpreted as meaning that the treatment has no value.

The research review was requested by CMS; Medicare covers 80% of a 3-month trial of CPAP for beneficiaries with a diagnosis of OSA, with continued coverage based on treatment compliance.

One recent study of Medicare recipients found that more than half (56%) were at high risk for OSA and possible candidates for treatment. Total Medicare spending on CPAP amounts to hundreds of millions of dollars annually.

"The big fear that I have, and many of my colleagues have, is that the way this report is worded could easily be misinterpreted as saying that prescribing CPAP doesn't improve these (long-term) outcomes, so we shouldn't be paying for it," said David Rapoport, MD, who directs the sleep medicine research program at the Icahn School of Medicine at Mount Sinai in New York City.

He said CPAP is widely recognized as the most effective treatment for improving OSA symptoms, such as snoring and daytime sleepiness.

"Nothing else even comes close," he said. "CPAP s really a remarkable treatment for addressing the breathing disorder associated with obstructive sleep apnea. But it has to be used, and compliance remains a big issue."

The AHRQ's Evidence-based Practice Centers (EPC) included data from 47 randomized clinical trials and other studies in their analysis reporting long-term (≥6 or 12 months) clinical outcomes in adult patients with OSA.

Investigators noted that the studies used "highly inconsistent" definitions of breathing measures, respiratory events, and response to treatment, measured using the Apnea-Hypopnea Index (AHI) -- a metric that the report also critiqued.

"No standard definition of this measure exists and whether AHI (and associated measures) are valid surrogate measures of clinical outcomes is unknown," the report states.

Report co-author Elise Berliner, PhD, of the AHRQ Center for Outcomes and Evidence, told MedPage Today that addressing the inconsistencies and limitations of the existing studies should be a top priority of the sleep research community.

She added that while the report does not address whether CPAP is overprescribed, it does call on the sleep research community to improve study designs by standardizing key measures such as AHI, CPAP compliance, and the definition of severe OSA.

"I do think the community needs to get together and figure out how to do better studies," she said. "We need larger and longer studies, and there is also the issue of compliance. In most of the studies, people were not using these devices all night long."

Berliner's group found that the existing randomized controlled trials provide low strength of evidence that CPAP affects all-cause mortality, stroke and myocardial infarction risk, or other cardiovascular outcomes. Researchers also concluded that insufficient evidence exists showing an impact for CPAP on the risk for automobile accidents, depression, and anxiety and hypertension.

Sanjay Patel, MD, of the University of Pittsburgh, agrees that lack of consistency and poor CPAP compliance in sleep studies have made it difficult to assess the treatment's impact on mortality and most other long-term outcomes.

But like Rapoport, he expressed concern that the draft report findings will be interpreted by some as suggesting that CPAP is an ineffective treatment.

"The thinking in the field has been that treatment may help prevent diseases like diabetes and heart disease that are related to sleep apnea," he told MedPage Today. "This report says we don't have good evidence on this, but it doesn't really distinguish between outcomes where we do and do not have enough research to say definitively that treatment with CPAP isn't beneficial."

Patel served on the writing committee for the American Academy of Sleep Medicine's latest clinical practice guidelines on the treatment of adults with OSA using positive airway pressure, which was published in 2019.

He noted that the updated guidelines differ from the AHRQ report in one key area, concluding that CPAP has been shown to lower blood pressure in OSA patients with comorbid hypertension.

The AHRQ analysis was restricted to people who were followed for more than 6 months, while the AASM's writing committee considered studies with shorter follow-up times.

"The effect [of CPAP] on blood pressure can be seen at 1 month," he said. "Multiple studies with 3 months of follow-up show improvements in blood pressure, but AHRQ did not look at those studies."

While CPAP is still considered the most effective treatment for OSA, Rapoport said there is a growing recognition within the sleep medicine field that it's not for everyone, given the ongoing issues with compliance.

"In the past, other treatments such as mandibular advancement devices have been marginalized," he said. "These treatments don't work nearly as well as CPAP in terms of lowering AHI, but they do work well for many patients, and people who are prescribed them actually use them. Until recently, there wasn't much acceptance that this was good enough. But there is now greater recognition that we should maybe be prescribing treatments that aren't perfect if people are more likely to use them."

Disclosures

The AHRQ Evidence-based Practice Centers investigators reported no relevant conflicts.

David Rapoport, who commented on the report, cited financial ties to the CPAP manufacturer Fischer and Paykel.

https://www.medpagetoday.com/pulmonology/sleepdisorders/92028