Russia plans to produce COVID-19 vaccine storable at fridge temperatures

 Russia plans to produce a form of its Sputnik V coronavirus vaccine that can be transported and stored at normal fridge temperatures as opposed to -18 Celsius, Health Minister Mikhail Murashko said on Thursday.

Such a move could help Russia in the global vaccine race by making it cheaper to store and transport Sputnik V, easing the logistical challenges posed by needing a colder supply chain and making it easier for developing nations to handle.

Murashko said one of six of its manufacturers had developed a form of the vaccine that was stable at a temperature of 2-8 Celsius in liquid form, though he gave no timeline for its production.

“The start of Sputnik V’s production with new storage conditions at one of our manufacturing platforms will allow us to expand coverage and increase the availability of the mass vaccination ... for the population,” Murashko said.

Two sources close to the manufacturing process said the variant would be produced by private Russian firm Generium. One source said production would start this quarter and require no significant additional investment.

Generium did not respond to a request for comment.

The issue of storage temperatures is a concern for countries. For example the vaccine developed by BioNTech and Pfizer, must be stored at ultra-low temperatures of about -70 degrees Celsius before being shipped to distribution centres in cool boxes filled with dry ice.

Alexei Kuznetsov, an aide at the health ministry, said the new form of the Sputnik V can currently be stored for three months, while the frozen vaccine that is kept at -18C has a six-month storage life.

Kirill Dmitriev, the head of RDIF, Russia’s sovereign wealth fund, which is promoting Sputnik V globally, said delivery logistics was a large cost for the vaccine and that it was a “great plus” to be able to store vaccines at 2-8 Celsius.

He did not say when the new form of the vaccine would be ready for export.

Sputnik V has also been developed in a powder form that can be stored at fridge temperatures, Kirill Dmitriev said earlier.

But two sources familiar with the matter said that production had not yet begun.

https://www.reuters.com/article/us-health-coronavirus-russia-vaccine-tem/russia-plans-to-produce-covid-19-vaccine-storable-at-fridge-temperatures-minister-idUSKBN29Q26F

Pfizer cuts vaccine deliveries by as much as half to some EU countries

 Pfizer has slashed in half the volume of COVID-19 vaccines it will deliver to some EU countries this week, government officials said on Thursday, as frustration over the U.S. drugmaker’s unexpected cut in supplies grows.

Romania got only 50% of its planned volume for this week, the other half being allocated gradually by the end of March, with deliveries returning to normal starting next week, Deputy Health Minister Andrei Baciu told Reuters.

It was a similar situation in Poland which on Monday received 176,000 doses, a drop of around 50% from what was expected, authorities said.

The Czech government was bracing for the disruption to last weeks, slowing its vaccination campaign just as second doses get under way.

“We have to expect that there will be a reduction in the number of open vaccination appointments in the following three weeks,” Health Minister Jan Blatny told reporters, with Pfizer deliveries falling by about 15% this week and as much as 30% for the following two weeks.

Pfizer and its German partner BioNTech have declined to comment on the cuts beyond their statement last week, which announced cuts to deliveries as they ramp up manufacturing in Europe.

Some countries reckon they can handle it. Norway has an emergency stockpile and will continue administering doses as planned, the government’s public health body said.

The U.S. drugmaker has told Bulgaria and Poland it will replace missing doses, top officials said.

But Denmark’s Serum Institute said its 50% loss of shots this week would lead to a 10% shortfall for the first quarter.

Italy, meanwhile, is threatening legal action against Pfizer, with COVID-19 special commissioner Domenico Arcuri saying on Thursday that the country has been told to expect a 20% cut next week after reducing this week’s supply by almost 30%

UNDERMINING EFFORTS

With governments across the region still reeling from the surprise cuts, officials say the reductions are undermining their efforts to inoculate their citizens and tame the pandemic which has killed more than 2 million people.

Adding to the upheaval are worries about supplies of special syringes needed to extract six doses from each vial of Pfizer’s shot.

Europe’s disease surveillance agency warned on Thursday that three variants of the coronavirus that emerged in Britain, South Africa and Brazil will lead to more COVID-19 infections, hospitalisations and deaths.

In Hungary, where the authorities gave the go ahead for the use of Britain’s AstraZeneca and Russia’s Sputnik V vaccines ahead of the EU drug regulator, a senior official called on Brussels to try and ensure deliveries from Pfizer and other vaccine makers would stick to schedule.

“We would be happy if the (European) Commission could take steps as soon as possible to ensure that Pfizer and other manufacturers would change deliveries,” Prime Minister Viktor Orban’s chief of staff Gergely Gulyas said.

The problem has spread to countries outside the trading bloc too - Canada is facing delays as is Switzerland, where the mountain canton of Grisons got only 1,000 shots from Pfizer this week, far short of the 3,000 it had been anticipating.

https://www.reuters.com/article/us-health-coronavirus-pfizer-europe/pfizer-cuts-vaccine-deliveries-by-as-much-as-half-to-some-eu-countries-idUSKBN29Q2BX

10 key clinical trials to watch in the first half of 2021

 Clinical trials are the proving ground for new and experimental medicines. Strong results can lead to regulatory approvals and change how diseases are treated, while weaker findings can dash hopes and close down testing. For biotech and pharmaceutical companies, clinical trial results are also the currency by which they convince investors, raise money and strike deals.

As the coronavirus pandemic worsens in the U.S. and in other countries around the world, the stakes are higher than ever for a number of clinical trials this year. Success from vaccines, antibody drugs and antivirals could help save lives and make COVID-19 a more manageable disease.

Important tests also await for drugs for depression, hemophilia, lung cancer and a rare disease called alpha-1 antitrypsin deficiency. As the first six months of 2020 unfold, keep an eye on these 10 clinical trials:

COMPANIES:

 

Johnson & Johnson, Novavax, AstraZeneca

DISEASE:

 

COVID-19

TREATMENT TYPE:

 

Vaccine

TRIALS:

 

ENSEMBLE (J&J), U.K. Phase 3 (Novavax), D8110C00001 (AstraZeneca)

WHY THEY'RE IMPORTANT:

Two coronavirus vaccines from Moderna as well as partners Pfizer and BioNTech are already authorized in the U.S and elsewhere. But both are challenging to distribute and their rollout has proved slower than anticipated. Supplies still remain extremely limited. Reinforcements could soon be on the way, however, if three Phase 3 trials produce positive results.

By the end of March, Johnson & Johnson, AstraZeneca and Novavax should each report efficacy data on their vaccines. The success, or failure, of each will be important for different reasons. J&J, for instance, is testing a one-shot regimen, which would be a boon for global vaccine supply. Novavax is advancing a protein-based vaccine, a more traditional approach than any on the market or close to it. And AstraZeneca — whose shot is cleared for use in the U.K. — has pre-sold some 300 million doses to the U.S. and hundreds of millions more to other countries around the world. In particular, the coming Phase 3 data for AstraZeneca's vaccine, from a 34,000-participant U.S. trial, could help clear up lingering questions about its effectiveness.

Novavax and J&J could deliver results before the end of January. AstraZeneca's are expected afterwards.

Editor's note: BioMarin disclosed one-year results from its Phase 3 trial of Roctavian late on Sunday, January 11.

COMPANY:

 

Biomarin Pharmaceutical

DISEASE:

 

Hemophilia A

TREATMENT TYPE:

 

Gene Therapy

TRIAL:

 

NCT03370913

WHY IT'S IMPORTANT:

Roctavian seemed set to become the first approved gene therapy for hemophilia, the culmination of decades of research into a one-time treatment for the chronic blood disease.

But the FDA in August surprisingly rejected Roctavian in one of the most stunning regulatory decisions in recent memory. Regulators, however, didn't turn back Roctavian because the therapy doesn't work. Instead, they flagged differences in results between two Roctavian studies. The treatment's effects appeared weaker in an initial group of participants enrolled in BioMarin's Phase 3 trial than it did in earlier testing, and waned over time.

In the EU, meanwhile, BioMarin withdrew its application after the European Medicines Agency requested more information.

Both agencies want to see more data, which is what makes BioMarin's coming update important. In January, the company is expected to report one year of follow-up data from its Phase 3 study. Should Roctavian's positive effects hold up, BioMarin could resubmit an approval application in Europe in the second quarter.

Roctavian's path back to an FDA review, however, is longer. The FDA required two years of follow-up, information BioMarin likely won't have until November.

COMPANY:

 

Amgen

DISEASE:

 

Lung cancer

TREATMENT TYPE:

 

Small molecule

TRIAL:

 

Codebreak 100

WHY IT'S IMPORTANT:

Drugmakers have spent decades trying to design a medicine that can treat cancer by blocking KRAS, a gene that's often mutated in several common tumor types. Amgen's sotorasib has a chance to become the first, which is why the drug has fast become the most valuable asset in the biotech's pipeline.

Sotorasib's most promising results so far have come in patients with advanced lung cancer — specifically for those whose non-small cell lung cancer has a specific mutation called KRAS G12C. Early data, for instance, showed treatment led to response rates roughly twice as high as what would be expected from chemotherapy.

In October, Amgen released a vague statement claiming, without details, that the drug had shown similar efficacy, safety and tolerability in Phase 2 testing. Those data were included in approval applications the company submitted to the FDA and EMA in December.

Amgen will finally unveil those results this month, when the company presents Phase 2 sotorasib results at the World Conference on Lung Cancer. The details could determine not only how widely the drug might be used in lung cancer, but how it stacks up against would-be competitors like Mirati Therapeutics. Amgen is also testing sotorasib in combination with other medicines, among them immunotherapies, making its profile as a single treatment important.

COMPANIES:

 

Merck & Co., Pfizer, Atea Pharmaceuticals/Roche

DISEASE:

 

COVID-19

TREATMENT TYPE:

 

Antivirals

TRIAL:

 

END-COVID (Merck), NCT04535167 (Pfizer), NCT04396106 (Atea/Roche)

WHY THEY'RE IMPORTANT:

The striking clinical success of two coronavirus vaccines has taken some of the spotlight away from other methods of treating or preventing COVID-19. Rollout of both shots, however, has been slow in the U.S., even as the pandemic has sharply worsened. Supplies are expected to be limited for some time, too.

In the meantime, then, anything that can help keep COVID-19 patients out of the hospital, shorten stays or prevent organ damage would be a major boost. That's what makes a group of experimental antiviral drugs by Pfizer, Merck, and partners Atea Pharmaceuticals and Roche worth keeping an eye on.

Each of these drugs could improve upon Gilead's Veklury, a repurposed Ebola drug that has modest benefits for hospitalized COVID-19 patients and has to be given intravenously over multiple days, limiting its potential for broader use. Pfizer's is a novel antiviral and has shown potential against multiple coronaviruses. Merck's drug, being developed alongside Ridgeback Biotherapeutics, is a pill, which could open up the option of earlier treatment outside hospitals. So is Atea's, a prospect that propelled the company to one of 2020's best biotech IPOs and a lucrative alliance with Roche.

According to the federal government database, a Phase 1b study of Pfizer's drug could produce results in April, while data from mid-stage studies of Merck's and Atea's treatments could come in March.

COMPANIES:

 

Sage Therapeutics, Biogen

DISEASE:

 

Depression

TREATMENT TYPE:

 

Small molecule

TRIAL:

 

WATERFALL

WHY IT'S IMPORTANT:

Last year was a difficult one for Sage. The Massachusetts biotech restructured, laid off half of its workforce and changed CEOs in the 12 months after its depression drug zuranolone failed a Phase 3 trial.

But Sage executives claim the drug still has a chance to become a valuable medicine. That's a belief apparently also shared by Biogen, which in November forged a $3 billion partnership with Sage that includes partial rights to zuranolone.

Sage executives blamed zuranolone's 2019 failure in major depressive disorder on several potentially confounding factors, and have since designed a slate of new Phase 3 studies — including two in MDD — to prove it. Three of those trials are expected to deliver results in 2021. The first is a study called Waterfall, which is testing zuranolone as an acute treatment of MDD. Data should come in the first half of the year, and will go a long way in telling whether zuranolone does indeed have a future.

COMPANY:

 

Vertex Pharmaceuticals

DISEASE:

 

Alpha-1 antitrypsin deficiency

TREATMENT TYPE:

 

Small molecule

TRIAL:

 

NCT04474197

WHY IT'S IMPORTANT:

Vertex was able to quickly recover when a once-promising hepatitis C drug franchise was wiped out in the mid-2010s because the biotech had a burgeoning cystic fibrosis business ready to take its place.

Success was achieved, in part, through a strategy that involved developing multiple, similar CF drugs simultaneously and picking the best one to take forward. The plan led to both Symdeko and Trikafta, which are now topp-selling drugs for the Boston-based drugmaker.

Vertex aims to follow its CF blueprint with another rare disease called alpha-1 antitrypsin deficiency, for which it had advanced multiple drugs in concert.

But the plan has already been put to the test. Last year, Vertex surprisingly scrapped a drug called VX-814 following worrisome safety signals in a Phase 2 trial, a setback compounded by the progress of fast-moving competition. Vertex has another drug in its arsenal, called VX-864, that it's said is structurally distinct from its failed predecessor.

A Phase 2 trial should produce results in the first half of 2021, the results of which could have big implications for Vertex going forward.

https://www.biopharmadive.com/news/biotech-10-clinical-trials-watch-2021-first-half/593069/

Addex Med Gets IND OK to Start Phase 2a Study in Epilepsy

  Addex Therapeutics (SIX: ADXN and Nasdaq: ADXN), a clinical-stage pharmaceutical company pioneering allosteric modulation-based drug discovery and development, today announced that its partner Janssen Pharmaceuticals, Inc., part of the Janssen Pharmaceutical Companies of Johnson & Johnson, has received FDA’s Investigational New Drug (IND) approval to begin a Phase 2a proof of concept study with the selective metabotropic glutamate type 2 (mGlu2) receptor positive allosteric modulator (PAM), JNJ-40411813 (ADX71149), in patients with epilepsy. The first patient is expected to be treated during Q2 2021.

“IND approval for the mGlu2 epilepsy study is great news to start 2021 and will be the first of three clinical studies we expect to be initiate this year,” said Tim Dyer, CEO of Addex. “There is a great opportunity for an allosteric modulation approach in this difficult disease. We’d like to thank the team involved for their continued support and moving quickly to get this clinical study ready for patient enrolment.”

The multi-center study will assess the efficacy, safety, tolerability and pharmacokinetics of adjunctive JNJ-40411813 (ADX71149) administration in patients with focal onset seizures with suboptimal response to levetiracetam. The primary objective of the study is to evaluate the efficacy of JNJ-40411813 (ADX71149) in combination with levetiracetam using a time-to-event endpoint.

“There is a strong preclinical rationale for mGlu2 PAM in epilepsy, including a true synergistic effect with levetiracetam,” said Robert Lütjens, Head of Discovery Biology of Addex. "A highly synergistic anti-epileptic effect was observed when the two drugs were administered together, and we look forward to seeing this effect in epilepsy patients.”

https://finance.yahoo.com/news/addex-adx71149-receives-ind-approval-060000495.html

In vitro test maker Ortho Clinical Diagnostics files $1.5B Nasdaq IPO

 Ortho Clinical Diagnostics is hoping to pay down a large portion of its debts by riding a wave of COVID-19 and broader in vitro lab testing demands to a $1.5 billion IPO. 

The company is offering 70 million shares on the Nasdaq—slated for the ticker OCDX—that are expected to be priced between $20 and $23 apiece in the coming week. Hitting the midpoint of that range would bestow a market value of $4.9 billion, according to Renaissance Capital.

Ortho produces the Vitros family of integrated, high-throughput testing systems, including for chemistry and immunodiagnostic applications—with an installed base of about 20,000 instruments, as of last fall—plus a suite of assays used for various diseases, blood transfusions and donor screening.

The company has also received emergency authorizations from the FDA for two COVID-19 antibody blood tests—and earlier this month obtained a green light for a high-volume antigen test capable of processing 130 samples per hour.

Its systems also include a platform that allows two tests to be run simultaneously on a single slide. The dual-test slides can pair up assays for commonly used diagnostics, such as ratios between blood urea nitrogen and creatinine, or triglyceride and cholesterol levels.

The company’s sales and testing volumes were hit by the pandemic, with net revenues over the first nine months of 2020 dropping about 5.9%, to about $1.25 billion compared with $1.33 billion over the same period the year before, according to Ortho’s prospectus. However, sales had begun to rebound in the last three of those months, through September 2020, with quarterly revenue growing by about 3.8% to 5.8%.

Formerly the diagnostics unit within Johnson & Johnson, Ortho was acquired by the global investment firm The Carlyle Group, following a $4.15 billion deal in 2014. Shortly after launching as an independent company, earnings dropped to a five-year low, and as of September 2020, Ortho had a total indebtedness of $3.7 billion.

The company plans to use the net proceeds from its IPO to repay about $1.28 billion of those borrowings, including by redeeming $160 million in senior notes due in 2025 and $270 million in notes due 2028.

The offering, first announced last October, is being made through an underwriting group led by J.P. Morgan, BofA Securities, and Goldman Sachs, who are joined by, Barclays, Morgan Stanley, Citigroup, Credit Suisse, UBS Investment Bank, Evercore ISI and Piper Sandler, ING, Macquarie Capital, Nomura, TCG Capital Markets, Drexel Hamilton, H.C. Wainwright & Co., Ramirez & Co., and Siebert Williams Shank. Ortho plans to grant the underwriters a 30-day option to purchase up to an additional 10.5 million ordinary shares at the IPO price, minus discounts and commissions.

https://www.fiercebiotech.com/medtech/vitro-test-maker-ortho-clinical-files-1-5b-nasdaq-ipo

Adagene plans $125M IPO to go after cancer niches targeted by Bristol, Pfizer

 Chinese cancer biotech Adagene has filed to raise up to $125 million in a Nasdaq IPO. The listing will give Adagene the means to run early-phase clinical trials of antibodies against CD137 and CTLA-4.

Adagene is built on a platform designed to expand the available binding sites well beyond what is possible with conventional natural or synthetic antibodies. Working with the platform, Adagene has developed candidates it thinks have an edge over other drugs targeting CD137 and CTLA-4.

Drug developers including Bristol Myers Squibb and Pfizer are working on drugs against CD137, the target of ADG106. What sets ADG106 apart, according to Adagene, is its targeting of a unique conserved epitope of CD137 that gives it a novel mechanism of action. An end of phase 1 meeting for a clinical trial of ADG106 in solid tumors is scheduled for this quarter.

Two drugs targeting CTLA-4, ADG126 and ADG116, are following Adagene down the pipeline. The drugs, both of which are in phase 1, are based on different technologies. Adagene plans to focus on ADG126, the first asset generated using its SAFEbody technology.

SAFEbody is designed to prevent an antibody from binding to its target in healthy tissues. Antibodies featuring the technology should only bind to their targets when exposed to conditions found in the tumor microenvironment. Adagene has applied the technology to CTLA-4 in the belief it can better the safety of existing antibodies against the target, notably Bristol Myers’ Yervoy.  

Around one-quarter of the IPO money will fund phase 1 development and the advancement into phase 2 for ADG106, with another quarter supporting the same work on ADG126 and ADG116. Most of the rest of the money is earmarked for the development of the platform and preclinical programs.

https://www.fiercebiotech.com/biotech/adagene-plans-125m-ipo-to-go-after-cancer-niches-targeted-by-bms-and-pfizer

NY governor investigates price jump in six drugs during pandemic

 New York Governor Andrew Cuomo said on Thursday the Department of Financial Services was investigating into a price jump of about 60% to 1,350% in six drugs during the COVID-19 pandemic.

New York has asked drug manufacturers to explain the large spike in prices of the drugs, which included dexamethasone, a treatment proven to decrease deaths in COVID-19 patients, and chloroquine phosphate, which was touted by former President Donald Trump as a cure, but turned out ineffective.

The price for Cipla USA Inc's Budesonide soared by over 1,350% during the first wave of the pandemic in the United States and on the heels of an announcement of clinical trials for its use against COVID-19, according to a statement released by the governor.

Jaguar Health increased the price of Mytesi, used for gastrointestinal side effects in HIV patients, by 230% just days after it applied for an emergency use authorization in COVID-19 patients, according to the statement.

It also shows that Nubratori Inc announced a price hike of over 65% for Dexonto, or dexamethasone, just 11 days before clinical trials on COVID-19 patients were announced in China.

Rising Pharmaceuticals' chloroquine phosphate saw its price surge 97.8% on "unsubstantiated reports of its effectiveness in treating COVID-19 patients," the statement said.

Hikma Pharmaceuticals' Duramorph, or morphine sulfate, experienced a rise of nearly 60%, while McGuff Pharmaceuticals raised price of Ascor by 110%, a week after clinical trials were announced for the ascorbic acid in COVID-19 patients with acute symptoms.

None of the companies was immediately available to respond to Reuters requests for comment.

The investigation was being handled by Department of Financial Services' newly formed Office of Pharmacy Benefits.

https://www.marketscreener.com/quote/stock/CIPLA-LIMITED-9058821/news/Cipla-NY-governor-investigates-price-jump-in-six-drugs-during-pandemic-32248429/