Merck agrees $1 billion deal with Debiopharm for head and neck cancer drug

 Germany’s Merck KGgA said on Monday it has agreed to pay Swiss biotech Debiopharm up to 900 million euros ($1.08 billion) to develop and commercialise Xevinapant for head and neck cancer.

Under the terms of the licensing deal, Merck will pay Debiopharm 188 million euros upfront and has agreed to further regulatory and commercial milestones worth up to 710 million euros, as well as royalties.

“This late-stage asset complements our Healthcare pipeline, which will be one of Merck’s key growth drivers in the coming years,” Chief Executive Stefan Oschmann said in a statement.

Xevinapant is currently in late-stage testing for previously untreated locally advanced squamous cell carcinoma of the head and neck, in combination with current standard of care.

Results of a mid-stage study found Xevinapant together with chemoradiotherapy cut the risk of death by 51% compared to the current standard of care, Merck said.

In February 2020, the U.S. Food and Drug Administration granted Xevinapant breakthrough therapy designation.

https://www.reuters.com/article/us-debiopharm-merck/merck-agrees-1-billion-deal-with-debiopharm-for-head-and-neck-cancer-drug-idUSKCN2AT2EK

In scramble for COVID-19 vaccine, Latin America turns to Russia

 As Bolivia struggled late last year to secure deals with large drug firms to supply COVID-19 vaccines, the incoming president, Luis Arce, turned to Russia for help.

By the end of December, Bolivia clinched its first major COVID-19 vaccine deal, with enough shots for some 20% of the population. The first Sputnik V doses arrived in the country in late January, just as virus cases were spiking.

“It was a really marathon task,” said Bolivian trade minister Benjamin Blanco of the procurement quest, but Russia’s political will made it possible. Western vaccine makers “told us developing countries that we had to wait until June.” He didn’t name names.

Bolivia’s reliance on Moscow underscores how governments across the region have turned to Russia’s Sputnik V drug amid fears of being left behind in the global scramble for vaccines. As many wealthier developed nations have signed big deals with large drugmakers like Pfizer Inc and AstraZeneca PLC, countries in Latin America have faced difficulties securing adequate vaccine supplies.

For Russia, acceptance in Latin America lends legitimacy to its vaccine, which faced initial skepticism. It also provides Moscow an opportunity to make in-roads in the resource rich region at a time when COVID-19 vaccines are becoming a tool for soft power. Sputnik V is named after the Soviet-era satellite that triggered the space race, in a nod to the project’s geopolitical importance for Russian President Vladimir Putin.

Latin America’s Russian gamble looks a stronger bet after scientists said it was almost 92% effective in its first peer-reviewed study, published in early February in international journal the Lancet.

Current and former officials from three countries in the region, including Blanco, described to Reuters challenges in negotiating with multinational drugmakers. Officials from two of the countries described the comparative ease in dealing with Sputnik V’s marketeers, ranging from eagerness to engage to less onerous contractual terms, and in some instances a more attractive price.

But it’s not without risk. It’s unclear how effective Sputnik is against the new coronavirus variants, including one circulating widely in Brazil. And Russia has already experienced production delays domestically and overseas, including to Argentina, which in December became the first Latin country to sign a Sputnik V supply deal.

Sharon Castillo, a spokeswoman for U.S.-based Pfizer, said in response to questions from Reuters that the company and its German partner BioNTech SE are committed to working with governments and others “to ensure equitable and affordable access to our COVID-19 vaccine for people around the world.” She added that Pfizer and BioNTech currently have completed bilateral supply agreements with eight countries in Latin America.

At least ten countries in the region have said they have signed deals to receive AstraZeneca’s vaccine, which is developed with UK’s University of Oxford.

Arce’s office didn’t respond to requests for comment. Bolivia has this year signed deals with a supplier of AstraZeneca’s vaccine as well as China’s Sinopharm and is procuring further doses via global vaccine-sharing scheme COVAX. Russia’s trade envoy to Bolivia, Iakov Fedorov, said the vaccine deal was “not so political” and the Russian government was “always predisposed to support and help” bring Bolivia together with Sputnik V’s marketers and manufacturers. Moscow’s Gamaleya Research Institute developed the drug, which the Russian Direct Investment Fund (RDIF) markets overseas.

RDIF agreed to supply 5.2 million shots of Sputnik V to Bolivia, enough of the two-shot vaccine for 2.6 million people. Bolivia has said it has received 20,000 shots of the vaccine.

The Kremlin and RDIF didn’t respond to requests for comment regarding Bolivia. Russia has said it is ramping up production hubs, mostly outside of the country. On Friday, RDIF said it had struck a deal with an Argentine company to produce Sputnik V locally.

On Jan. 19, Arce spoke with Putin. The two leaders discussed reviving Russian investments in Bolivia to develop gas reserves, rekindling a nuclear plant project and cooperating on lithium mining, Blanco said.

Federov, the Russian trade envoy, said they discussed reactivating ties and investments. Vaccine cooperation with Bolivia “can contribute to bilateral and regional relations,” he added.

RDIF has announced deals in at least six Latin American countries to supply more than 60 million shots, according to a Reuters tally of available data. Other countries in the region have said they are looking at Sputnik V.

RDIF has said it has deals to deliver doses to more than 500 million people this year. Russia recently offered 300 million Sputnik V doses to Africa along with a financing package for countries wanting to secure the shots.

‘TOUGH’ TALKS

Bolivia has recently experienced a deadly surge in COVID-19 infections, leaving corpses piling up amid overwhelmed funeral homes and cemeteries. A country of about 11.5 million people, Bolivia has reported more than 11,600 COVID-19 related deaths, according to a Reuters tally.

But Bolivia, one of Latin America’s poorest nations, has struggled to secure bilateral deals for vaccine supply. After Arce took office in early November, the socialist Bolivian government entered into discussions to obtain AstraZeneca’s vaccine. Blanco described those talks as “difficult” and “intense,” though declined to give more details, citing a confidentiality agreement. The talks were led by India’s Serum Institute, which is a manufacturer of AstraZeneca’s vaccine. Bolivia in January struck a deal with the Serum Institute for 5 million doses, which are not due to arrive until April.

AstraZeneca said its role was to connect the Bolivian government with the Serum Institute.

Blanco said Bolivia wasn’t able to negotiate with Pfizer because the country lacked infrastructure to store the vaccines at the low temperatures required.

The minister added that Bolivia was seeking a small share of Pfizer’s vaccine via global vaccine-sharing scheme COVAX, which is backed by the World Health Organization and involves various suppliers. Arce’s government agreed in January to receive 5.1 million doses of a range of vaccines from COVAX; the first batch of around 1 million doses the government said were due to arrive by the end of February. Blanco said that even via COVAX, Bolivia had to meet numerous requirements, including guaranteeing payment of transportation and logistics costs.

Pfizer spokeswoman Castillo said the company pays for transport and logistics costs from its plant to the recipient nation, which is then responsible for such costs “once in-country.”

Officials from some countries, including Argentina and Peru, have publicly complained that terms demanded by Western drugmakers were too tough, including liability waivers and long confidentiality clauses.

Two of the regional officials told Reuters about frustration among countries in the region over delays in locking in deals with Johnson & Johnson, which hasn’t announced any finalized bilateral deals in the region. The U.S. drugmaker conducted trials in six Latin American countries late last year for its single-shot vaccine, which doesn’t require cold storage. J&J said it is “committed to enabling equitable global access to the Janssen COVID-19 vaccine candidate on a not-for-profit basis for emergency pandemic use, if approved for use by health authorities.”

Blanco said key differences in dealing with Russia included its offer to accept liability for any problems, unlike other drugmakers.

Pricing was another differentiator, said Blanco, with Russia offering a single price of around $10 per jab. Pfizer is charging some buyers, including in European Union and the United States, around $19 per shot, as Reuters has previously reported. One of the Latin American officials said AstraZeneca’s vaccine cost between about $3 and $5 a dose.

Pfizer declined to confirm the cost but said lower income countries would pay a not-for-profit price.

https://www.reuters.com/article/us-health-coronavirus-latam-russia-insig/amid-scramble-for-covid-19-vaccine-latin-america-turns-to-russia-idUSKCN2AT23J

Widely shared vitamin D-COVID-19 preprint removed from Lancet server

 A preprint promoted by a member of the UK Parliament for claiming to show that vitamin D led to an “80% reduction in need for ICU and a 60% reduction in deaths” has been removed from a server used by The Lancet family of journals.

The preprint, “Calcifediol Treatment and COVID-19-Related Outcomes,” was posted to Preprints with The Lancet on January 22. On February 13, David Davis, a Conservative member of UK’s Parliament, tweeted:

The tweet has been retweeted and liked tens of thousands of times. Almost immediately, the paper began attracting criticism, particularly about its claims to have been a randomized study. Here’s one comment on the preprint site:

Although the paper claims it is a randomised study, it also says that all patients treated in 5 wards received calcifediol treatment, while all three of the other wards received no calcifediol. How this study can be considered randomised is therefore questionable (maybe the wards were randomised but that is a very poor level of randomisation). It is also presumably open label, meaning that the attending physicians and decision makers would have been well aware whether the patients were receiving calcifediol or not. Its concerning to me that that in the calcifediol group more patients apparently died than were referred to the ICU. In the control group approx. 50% of the patients referred to the ICU died (assuming all those who died were ICU patients). This raises some troubling questions about the decision making process in the calcifediol group, were patients not referred to ICU who should have been?

Others, including Aurora Baluja, an anesthesiologist and critical care doctor in Spain, raised concerns on Twitter. And on February 15, The Lancet Infectious Diseases asked Baluja for an “urgent” review of the paper. 

In that review, which Baluja has posted to Github, she raises questions about the alleged randomization, and also whether the trial was properly registered — a requirement for publication by most medical journals. Baluja also asked for the preprint to be taken down from The Lancet’s servers and posted instead to medRxiv, “to allow for continuous improvements and extensive prepublication review.”

Today, The Lancet Infectious Diseases removed the preprint, replacing it with:

We have removed this preprint due to concerns about the description of the research in this paper. This has led us to initiate an investigation into this study.

The comments that have been posted on this preprint will remain available on this page. Please note that this comment thread is now closed to further posts.

This is the 85th paper about COVID-19 that has been retracted or withdrawn, according to our records.

Nick Brown, who brought the preprint to Baluja’s attention, tweeted:

https://retractionwatch.com/2021/02/19/widely-shared-vitamin-d-covid-19-preprint-removed-from-lancet-server/

BridgeBio : FDA Approves NULIBRY To Reduce Risk In Neurological Disease

 BridgeBio Pharma Inc. (BBIO) and affiliate Origin Biosciences Inc. said that the U.S. Food and Drug Administration has approved NULIBRY or fosdenopterin for Injection as the first therapy to reduce the risk of mortality in patients with molybdenum cofactor deficiency or MoCD Type A.

Molybdenum cofactor deficiency Type A is an ultra-rare and progressive condition, known to impact less than 150 patients globally with a median survival of four years. MoCD Type A presents shortly after birth, often with severe encephalopathy and intractable seizures. NULIBRY is a first-in-class approved cPMP substrate replacement therapy.

MoCD Type A is an autosomal recessive, inborn error of metabolism caused by mutations in the molybdenum cofactor synthesis 1 gene and characterized by a deficiency in molybdenum cofactor production, leading to a lack of molybdenum-dependent enzyme activity. The lack of activity leads to decreased sulfite oxidase activity with buildup of sulfite and secondary metabolites in the brain, which causes irreversible neurological damage.

https://www.nasdaq.com/articles/bridgebio-%3A-fda-approves-nulibry-to-reduce-risk-of-mortality-in-patients-with-mocd-type-a

McKesson begins distribution of Johnson & Johnson's COVID-19 vaccine

 U.S. drug distributor McKesson Corp said on Monday it had begun distribution of Johnson & Johnson’s COVID-19 vaccine.

The vaccine became the third authorized COVID-19 vaccine in the United States over the weekend, following Friday’s unanimous endorsement by the Food and Drug Administration’s panel of outside experts.

McKesson is the partner for the U.S. government’s COVID-19 vaccine distribution and the company has established four distribution centers which will be specifically used to distribute the Johnson & Johnson COVID-19 vaccine.

The U.S. government makes the administration decisions, including where, when and how many vaccine doses McKesson will distribute, the company said.

Initial deliveries of the vaccine should begin on Tuesday, senior Biden administration officials had said on Sunday.

https://www.reuters.com/article/us-health-coronavirus-johnson-johnson-mc/mckesson-begins-distribution-of-johnson-johnsons-covid-19-vaccine-idUSKCN2AT263

Another Cuomo Cover-Up

 At last, Joe Biden, Anthony Fauci and CNN are no longer presenting New York Democrat Andrew Cuomo as the model governor in pandemic response. The question now is how many lives were lost due to his reckless policy of forcing vulnerable populations to accept greater risk of infection—and then hiding the results. Nursing homes were not the only places forced to accept Covid-positive patients.

Maria McFadden Maffucci writes at National Review: “Cuomo’s edicts put another vulnerable population in inexcusable peril: New Yorkers with intellectual and developmental disabilities (IDD) living in group homes.” Ms. Maffucci writes:

You know that notorious March 25 order, sending contagious nursing-home patients back to their homes from hospitals? Well, it had a twin. An April 10 memo from the Office of People with Developmental Disabilities (OPWDD) to operators of certified residential facilities had identical language to the nursing-home memo, to wit: “No individual shall be denied re-admission or admission to a Certified Residential Facility based solely on a confirmed or suspected diagnosis of Covid-19. . . . Additionally, providers of Certified Residential Facilities are prohibited from requiring a hospitalized individual, who is determined medically stable, to be tested for [Covid-19] prior to admission or readmission.”

Guess how that worked out for disabled New Yorkers. As is Cuomo custom, the state government withheld crucial information from public disclosure. Therefore scientists and policy makers had to try to make sense of limited data. Ms. Maffucci says that researchers often had to rely on voluntary reporting from advocacy organizations.

The available data told another highly disturbing story. Last year a study in Disability and Health Journal titled “COVID-19 outcomes among people with intellectual and developmental disabilities living in residential homes in New York state” reported some dismal statistics:

People with IDD living in residential group homes were at greater risk of severe COVID-19 outcomes: case rates – 7,841 per 100,000 for people with IDD compared to 1,910 for New York State; case-fatality – 15.0% for people with IDD compared to 7.9% for New York State; and mortality rate – 1,175 per 100,000 for people with IDD compared to 151 per 100,000 for New York State.

If the Cuomo government ever allows a full accounting, perhaps researchers can estimate the precise impact of the directive to facilities on accepting Covid-positive patients.

The overall policy may live forever in the annals of bureaucratic cruelty. At the same time the Cuomo administration was turning down offers to expand treatment space for Covid patients—and instead forcing them into group homes, raising the risks for disabled residents there—Team Cuomo was also severely limiting family visits at such facilities. In other words, official Cuomo administration policy required people with disabilities to accept both greater risk of infection by strangers and less time with relatives. Last July James Bernstein wrote in Long Island’s Long Beach Herald:

On Father’s Day this year, Dan Mulvaney used his [iPad] to tap out a note to his mother in Long Beach: “How long until I’m free...unfair...I’m ok. Ask state. So tired of lockdown...make change for all.”

...Mulvaney is autistic, and lives with three others in a group home in Baldwin. Since the coronavirus pandemic, he and all the others in homes for the developmentally-disabled on Long Island and across the state, have been living under strong restrictions, their relatives say.

Only since Father’s Day weekend have the group home residents been allowed to receive visitors, for 30 minutes only... Before, no visits were allowed, and the residents were permitted outside only in the company of an aide, for a walk down the block.

The added bureaucratic insanity of this situation was that Mr. Mulvaney had already been infected and had already recovered from Covid. Yet state policy was still restricting his mobility and ability to see loved ones. Of course he was not the only one forced to endure a terrible isolation. The Herald’s Mr. Bernstein reported on another family:

... all Lloyd Groveman of Old Westbury knows is that the restrictions have been hard on his son, Jack, 18, who is autistic and lives in a group home In Lido Beach.

“He doesn’t understand the concept” of the restrictions, Groveman said. “It is cruel and unusual circumstances.” Groveman said that in the months of the pandemic, he has been able to see his son only twice. When he did see his son, Groveman said, “He would run to the window. He was happy to see us. He wants to leave” the house.

Ms. Maffucci notes that during that same month the Cuomo administration finally issued less restrictive rules. But the resistance to public disclosure continued.

“Why Such Secrecy?,” asked a headline in the Albany Times-Union in November. The newspaper editorialized:

Last week, an advocacy group, Disability Rights New York, filed suit to get long-delayed information from the Office of People with Developmental Disabilities on how many group home residents and staff have been infected with or died from the virus -- a delay the group said hampers the ability to minimize the risk of infection in a vulnerable population and assess the state’s efforts to protect it.

At a time when residents and businesses are being called to a common fight to slow the coronavirus’ spread, the state’s selective secrecy only feeds and validates the speculation that there are things the Cuomo administration is purposely trying to hide -- in particular, that it’s not necessarily living up to its tough standards for employers and high-minded talk of a shared burden.

When will a tough standard be applied to Mr. Cuomo, who imposed some of the country’s most dangerous burdens and then prevented the public from learning about the resulting destruction?

https://www.wsj.com/articles/another-cuomo-cover-up-11614029575

Rare Diseases Have Significant Economic Impact Each Year in US

 The National Economic Burden of Rare Disease Study conducted on behalf of the EveryLife Foundation for Rare Diseases took a first-of-its-kind look at the economic burden of rare diseases in the United States for the year 2019.

Because the study only examined the financial costs of 379 rare diseases, Annie Kennedy, Chief of Policy and Advocacy at EveryLife Foundation said the research is “only the tip of the iceberg” of the overall economic burden in the rare disease community. In an interview with BioBuzz ahead of the study’s release, Kennedy said it was critical to establish the hard data in order to ensure the conversation can move from “anecdotal evidence to what the actual economic cost of rare disease is.”

The study includes both direct medical costs, as well as indirect costs that affect the families of these patients. Of that $966 billion, $418 billion (43%) was in direct medical costs, while $548 billion (57%) was in indirect costs, the study shows. Direct medical costs include inpatient and outpatient services and prescription medications, while indirect medical costs include employee absenteeism, forced retirement, and healthcare services not covered by insurance.

Kennedy said it was important for this study to show the indirect costs since so many of these are silently borne by the families of the patients. Prior to the study, Kennedy, a longtime advocate for the rare disease community, said they were not surprised the indirect economic burden was higher than the direct costs of rare diseases.

“For families, these are costs that accumulate. This is a one-year snapshot and it doesn’t show the whole picture of living with rare disease,” Kennedy said. “There’s so much more to this story.”

The survey shows that on average, the per-person excess direct medical cost of rare disease is $26,887 more than that for comparison individuals without a rare disease. The average annual direct medical excess cost for a child with a rare disease is $32,037, $29,647 for working-age adults with a rare disease, and $21,772 for rare disease patients age 65 and older.

The highest per-person excess medical cost is for “Lysosomal storage diseases” regardless of the age group. The study shows the cost breakdown at $132,757 for children and $54,996 for adults. The second most expensive rare disease group among children based on per-person excess costs is “Other endocrine or metabolic disorders,” which has an average excess medical cost of $72,285. Among adults, the second most expensive group is “Diseases of the blood and blood-forming organs,” which has an average cost of $52,201.

The estimated total indirect and non-medical cost of rare disease was $548 billion in 2019, with $343 billion to persons with rare diseases and another $205 billion to unpaid caregivers.

To create the study, EveryLife Foundation, a rare disease policy organization based in Washington, D.C., had more than 100 patient organizations work with them to identify data points to collect. The organization conducted a survey of rare disease families and received a response from 3,484 households. Of those, 1,409 (40.4%) completed the survey.

Of those 39 respondents were not included because the name of the disease entered was not considered a rare disease, which is defined by the Orphan Drug Act of 1983 as a condition that affects fewer than 200,000 people in the U.S. The diseases included in the new report include some of the more prevalent rare diseases, such as cystic fibrosis and hemophilia, but also included ultra-rare diseases, Kennedy said.

The National Institutes of Health estimates there are between 25 million and 30 million Americans living with a rare disease. Although it is expected there are about 7,000 rare diseases, only a few in the U.S. are actually tracked with International Classification of Diseases (ICD) codes.

That lack of ICD codes is a significant issue Kennedy and the rare disease community hope to address. Currently, only about 500 rare diseases have such codes. That lack of codes for the other 6,500 rare diseases makes diagnostics, access to care, and therapeutics difficult, Kennedy said.

On Thursday, Kennedy and her team released the data during a high-level presentation with the Rare Disease Caucus in the U.S. House of Representatives. Ahead of the meeting, she said she planned to go into detail about the economic burdens in hopes of incentivizing biomedical investment from the U.S. government, particularly the NIH and the U.S. Food and Drug Administration.

“We really need to begin to drive funding and policy to better align with the public health impact of rare disease,” Kennedy said. “The funding prioritization for rare disease does not meet what’s going on with pharma, the NIH, the FDA and others.”

Although the rare disease community in the U.S. has traditionally enjoyed bipartisan support from Congress, Kennedy said she hopes this economic data impact study will spur more support for the community. Next week, rare disease advocates from across the country, armed with the economic impact data, will meet with members of Congress in hopes of appropriating the authorization for the appropriate funding levels needed in rare disease. Kennedy said the 2019 economic snapshot will serve as a springboard for the community.

“We’re only getting started,” she said.

https://biobuzz.io/rare-diseases-have-significant-economic-impact-each-year-in-the-united-states/