Biotech Investors: Mark Your Calendar For December PDUFA Dates

 A majority of verdicts handed down by the FDA in November were positive. Three new molecular entities were approved during the month, taking the total number of NME approvals for the year-to-date period to 45. This is just one short of NME approvals received for the same period last year.

NME approvals are important as they are indicators of innovation in drug research. NMEs are drugs containing an active moiety that has never been approved or marketed in the U.S.

PDUFA date is a binary catalyst that can result in huge stock moves in either direction. It's the date by which the FDA is required to issue its verdict on the approvability/non-approvability of the drug following a review period that can span from six months to 10 months, depending on whether it is a standard review or priority review.

Here are the key PDUFA dates scheduled for December.

Merck's Wonder Cancer Drug On Track For Another Label Expansion

• Company: Merck & Co., Inc. 
  MRK -0.73%
   (Get Free Alerts for MRK)
• Type of Application: supplemental biologic license application
• Candidate: Keytruda
• Indication:
• Date: Dec. 4

Keytruda was evaluated in a two-part Phase 3 trial dubbed KEYNOTE-716 for the adjuvant treatment of patients with completely resected high-risk stage II melanoma. Interim analysis of data from the study released in early August showed statistically significant and clinically meaningful improvement in recurrent-free survival.

Dare Seeks Nod For Its Bacterial Vaginosis Treatment

• Company: Daré Bioscience, Inc. 
  DARE -0.59%
   (Get Free Alerts for DARE)
• Type of Application: new drug application
• Candidate: Dare-BV1
• Indication: bacterial vaginosis
• Date: Dec. 7

Dare's NDA for Dare-BVI for the proposed indication of bacterial vaginosis was accepted for priority review on Aug. 9. DARE-BV1 is a unique hydrogel formulation of clindamycin phosphate 2% to treat bacterial vaginosis via a single application.

Can Calliditas' Kidney Inflammation Drug Find Favor With FDA?

• Company: Calliditas Therapeutics AB (publ) 
  CALT -0.11%
• Type of Application: NDA
• Candidate: Nefecon
• Indication: IgA nephropathy
• Date: Dec. 15

Nefecon is a patented oral formulation of budesonide – for targeted release. The formulation is designed to deliver the drug to the Peyer's patch region of the lower small intestine, where the disease originates, as per the predominant pathogenesis models.

Nefecon is derived from the TARGIT technology, which allows for the substance to pass through the stomach and intestine without being absorbed, and to be released in a pulse-like fashion only when it reaches the lower small intestine.

IgA nephropathy, also known as Berger's disease, is a kidney disease that occurs when IgA deposits build up in the kidneys, causing inflammation that damages kidney tissues. IgA is an antibody made by the immune system to protect the body from foreign substances such as bacteria or viruses.

The original PDUFA of Sept. 15 was extended by three months to allow time for review of additional information submitted by the company on estimated glomerular filtration rate, upon FDA's request.

Can Second Time Be Charm For Eagle?

• Company: Eagle Pharmaceuticals, Inc. 
  EGRX +1.55%
• Type of Application: Abbreviated NDA
• Candidate: Vasopressin
• Indication: hypotension
• Date (Generic Drug User Fee Act date): Dec. 15

Eagle is seeking approval for a generic version of Vasostrict, which is marketed by Endo International Plc's 

ENDP +0.19%

 Par unit and had total U.S. sales of $786 million in 2020. The ANDA was accepted for priority review and the FDA rejected the application with a complete response letter in Feb. 2021.

Eagle's response to the CRL was submitted on June 15 and the FDA assigned a GDUFA date of Dec. 15. Contingent on FDA approval, the company expects a commercial launch prior to year-end.

Intra-Cellular Looks Forward To Twp Label Expansion For Depression Drug

• Company: Intra-Cellular Therapies, Inc. 
  ITCI +0.21%
• Type of Application: supplemental NDAs
• Candidate: Caplyta
• Indication: bipolar depression
• Date: Dec. 17

Caplyta, 42mg/day, is an oral, once daily atypical antipsychotic approved for the treatment of schizophrenia of adults. The treatment, which goes by the generic name lumateperone, is currently being evaluated for bipolar depression, depression and other neuropsychiatric and neurological disorders.

The FDA accepted the sNDA seeking approval for lumateperone for depressive episodes associated with bipolar I or II disorder as monotherapy and as adjunctive therapy with lithium or valproate in early May.

Argenx Knocks The FDA Door For Its Antibody Treatment For Autoimmune Disorder Causing Muscle Weakness

• Company: argenx SE 
  ARGX +3.98%
   & Zai Lab Limited 
  ZLAB +0.29%
• Type of Application: BLA
• Candidate: Efgartigimod
• Indication: generalized myasthenia gravis
• Date: Dec. 17

Argenx' regulatory application for its lead drug Efgartigimod was accepted for a standard review in early March. It's an investigational antibody fragment designed to reduce disease-causing immunoglobulin G.

Myasthenia gravis is a rare and chronic autoimmune disease, often causing debilitating and potentially life-threatening muscle weakness. There are approximately 65,000 people in the U.S. and 20,000 people in Japan living with the disease

Can Amgen's Otezla Snag Another Approval?

• Company: Amgen, Inc. 
  AMGN +0.18%
• Type of Application: sNDA
• Candidate: Otezla
• Indication: plaque psoriasis
• Date: Dec. 19

Amgen announced FDA acceptance of the application for review on May 5, and this time around, the company has applied for approval of the drug for the treatment of adults with mild-to-moderate plaque psoriasis who are candidates for phototherapy or systemic therapy.

Veru Hopes to Secure FDA Win With Maiden Regulatory Filing

• Company: Veru, Inc. 
  VERU +0.58%
• Type of Application: NDA under 505(b)(2) regulatory pathway
• Candidate: Tadfin (Tadalafil and Finasteride combo)
• Indication: benign prostatic hyperplasia
• Date: Dec. 23

Tadfin, (tadalafil 5mg and finasteride 5mg) capsules, is an oral daily dosing combination formulation for the treatment of benign prostatic hyperplasia, also called as prostate gland enlargement.

Tadfin is Veru's first PDUFA filing and therefore the company received a waiver of the FDA NDA PDUFA filing fees, worth approximately $2.4 million in cost savings, as a first-time filer.

If approved, the company currently plans to launch Tadfin through third-party telemedicine sales channels, and out-licensing opportunities thus eliminating the need for and cost of a direct sales force.

Aquestive Hopes To Clear FDA Hurdle On Second Try

• Company: Aquestive Therapeutics, Inc. 
  AQST -5.45%
• Type of Application: NDA
• Candidate: Libervant
• Indication: seizure clusters
• Date: Dec. 23

Libervant faltered once at the FDA altar, with the receipt of complete response letter for Aquestive's original regulatory filing in September 2020. The regulator had taken exception to certain weight groups showing a lower drug exposure level than desired.

On July 19, Aquestive announced the FDA accepted its resubmission, deeming it as a complete response.

Libervant, if approved by the FDA for U.S. market access, will enable a larger share of patients to receive more appropriate treatment by providing consistent therapeutic dosing in a non-invasive and innovative treatment form for epileptic seizures, the company said.

Bristol-Myers Squibb Seeks Approval For First Preventive Treatment For Acute Graft Versus Host Disease

• Company: Bristol-Myers Squibb Company 
  BMY +0.84%
• Type of Application: sBLA
• Candidate: Orencia
• Indication: acute graft versus host disease
• Date: Dec. 23

Bristol-Myers Squibb is seeking approval for Orencia (abatacept) for the prevention of moderate to severe acute graft versus host disease in patients 6 years of age and older receiving unrelated donor hematopoietic stem cell transplantation.

If approved, Orencia would become the first therapy for the prevention of aGvHD, the company said.

Global Blood Targets Twin Approvals For Its Sickle Cell Disease Drug

• Company: Global Blood Therapeutics, Inc. 
  GBT +6.56%
• Type of Application: sNDA/NDA
• Candidate: Oxbryta
• Indication: sickle cell disease
• Date: Dec. 25

The FDA has accepted for filing and review the company's sNDA, seeking accelerated approval for Oxbryta for the treatment of SCD in children ages 4 to 11 years and its NDA seeking approval for a new age-appropriate dispersible tablet dosage form of Oxbryta suitable for pediatric patients.

Oxbryta, which directly targets hemoglobin polymerization, the root cause of red blood cell sickling in SCD, is currently approved by the FDA in a tablet dosage form to treat SCD in patients age 12 years and older.

Coherus Awaits Nod For Its Humira Biosimilar

• Company: Coherus BioSciences, Inc. 
  CHRS +1.12%
• Type of Application: 351(k) BLA
• Candidate: CHS-1420
• Indication: Autoimmune disorders
• Biosimilar Use Fee Date: December

CHS-1420 is Coherus' biosimilar for AbbVie, Inc.'s

ABBV +0.8%

 best-selling drug Humira. Humira fetched over one-third revenues for AbbVie in the third quarter.

"If approved, Coherus plans to launch the adalimumab biosimilar in the U.S. on or after July 1, 2023, per the terms of an agreement with Humira manufacturer AbbVie," the company said in February, when it announced the acceptance of the BLA.

Adcom Meeting

FDA's Cardiovascular And Renal Drugs Advisory Committee is scheduled to meet on Dec. 8 to discuss Reata Pharmaceuticals, Inc.'s 

RETA -5.63%

 NDA for bardoxolone methyl capsules for the proposed indication of slowing the progression of chronic kidney disease caused by Alport syndrome in patients 12 years of age and older.

https://www.benzinga.com/general/biotech/21/12/24351192/attention-biotech-investors-mark-your-calendar-for-december-pdufa-dates

Israel halts controversial tech to track omicron variant

 Israel said Thursday it was halting the use of a controversial phone tracking technology to trace possible cases of the new coronavirus variant, days after it was authorized as an emergency measure

Earlier this week, the government announced a package of emergency measures to contain the new variant, including travel restrictions and authorizing the country's internal security agency to use the phone monitoring technology for contact tracing people infected by the omicron variant.

The tracking was authorized under emergency regulations and would have required parliamentary legislation in order to continue the practice.

But late Thursday, Prime Minister Naftali Bennett's office said the "cellular monitoring" would expire at midnight and not be extended.

The reversal came following days of public criticism of a practice whose use in the past has been criticized by civil liberties groups and challenged in court. Several Cabinet members voted against using the technology, and a government ombudsman argued that it was ineffective.

Health Minister Nitzan Horowitz said on Twitter that "from the beginning I noted that use of this tool would be limited and brief—for a few days, in order to get urgent information to halt infection with the new, unknown variant."

He said that "alongside protecting health, we must protect privacy and human rights, even in a time of emergency."

Israeli rights groups have decried the use of the technology, which can track where a person has been and whom he has met, as a violation of privacy rights. The Supreme Court ruled earlier this year that its use be limited.

Earlier Thursday, the court rejected a petition by a rights group against the reintroduction of phone tracing, noting the limited scope of its authorization and the uncertainty surrounding the omicron variant.

The Association for Civil Rights in Israel welcomed Thursday's decision and expressed "hope that this is the last time the secret service will be used to monitor the citizens of the State of Israel."

Israel's Health Ministry has confirmed three cases of the new omicron variant of COVID-19, and said Thursday that nearly three dozen other possible cases are being tested.

Israel, a country of 9.3 million people, has reported 8,199 deaths from the coronavirus since the start of the pandemic. Most of its population—over 6.3 million people—has received at least one dose of the Pfizer/BioNTech vaccine, and more than 4 million Israelis have received a booster.

https://medicalxpress.com/news/2021-12-israel-halts-controversial-tech-track.html

Many vaccine passports have security flaws – here's how to make them safer

 COVID vaccination passports have proved extremely divisive during the coronavirus pandemic, due to issues relating to civil liberties or their potential to discriminate against the more vaccine-hesitant groups within society

But as many governments around the world push forward with their implementation in an attempt to curb the spread of COVID-19, the security of our data has become a major cause for concern.

Many COVID passes work by producing a QR code or 2D barcode for each user that can be scanned as proof of vaccination. The barcodes used in some of these passports are not that secure because they are not generated with encrypted data. However, they could be made secure if national governments, international organizations and global tech companies work together to make the most of the exciting possibilities this technology presents.

Embedded within the barcode is a verifiable credential which proves vaccination status, and a number of personal details depending on the barcode's format. These are likely to include the user's full name and date of birth. To ensure authenticity and prevent fraud, the barcode also contains a unique digital signature which is generated based on its contents.

A number of vaccine passport programs have already come under fire for a lack of security, including those in New York and Quebec, which have been criticized for allowing people to obtain other people's barcodes by entering their details. To mitigate some concerns, the EU has established its own open standard for vaccine passports—the EU Digital COVID Certificate (EUDCC). It has been adopted by the 27 EU states and 18 other countries.

However, this hasn't addressed the fact that the contents of the certificate are not encrypted, so anyone with access to the barcode (and the necessary skills) can decode it and retrieve the personal information contained within. This applies to COVID passports in the EU, Canada, UK, California and New Zealand. There are only slight differences in how the data is encoded—but in all these cases it is not encrypted.

To encrypt the COVID certificate's contents, there must be what's known as an encryption key associated with the certificate and the owner's digital identity. Currently, most COVID barcodes do not encrypt their contents due to the lack of digital identity infrastructure as well as the requirement to operate offline. This puts a user's personal information at risk.

There is also another problem with the current COVID certificates. They are signed by the issuer (for example the NHS) using a region- or country-specific key, or code. If someone should attain the key, they could create a false certificate. The authorities would have to respond to the fraudulent COVID passports by revoking the compromised key, which would mean that all preexisting COVID certificates would become invalid.

Why use barcodes

Up until recently, digital identity management for a computer user has consisted of a simple username and password credential. It's a system that has worked, in the main, for more than 60 years. But the current explosion in online content, cybersecurity challenges and privacy concerns are driving the need for a user to have more control of their own digital identity.

Our identity is essentially made up of millions of small truths about ourselves. Verifiable credentials in a barcode could enable us to share just a single truth rather than our whole identity, to suit the particular situation if the data is adequately encrypted.

To its credit, the COVID certificate does just that. It is a simple proof of an individual truth, in theory enabling you to demonstrate you have been vaccinated without giving any other details away. The fact that the certificate is not entirely secure indicates the absence of a more robust digital identity infrastructure.

Potential risks

The absence of this piece of the digital identity puzzle must be rectified at some point in the future. Until then, the current COVID passports could be open to abuse.

The personal information involved in the vaccination certificate is not particularly sensitive at face value, because it is often easily found in other places such as a driver's license, school records or passport. But in the future, when this technology is more widespread, we will probably be using similar certificates which contain verifiable credentials in pretty much every aspect of our lives—such as to access a building or services, or to approve purchases (both instore and online).

This has positive and negative consequences for users. On the plus side, we will only need to provide the minimum amount of personal information in a very user friendly way. For example we will be able to sign up to websites without even entering a name.

But if we present non-secure barcodes in many places, each containing small single truths about ourselves, then eventually these can potentially be combined together and the identity of the individual to whom they relate may be compromised.

This is how many cybercriminals currently work, combining data from different sources of information, which allow a person's digital identity to be constructed over time. This could lead to an increased risk of identity theft, and potentially be used as a basis for a variety of cybercrimes.

However for all these concerns about digital passports, we should remember that if it can be made secure on an international scale, this kind of digital identity technology has significant potential upside for citizens—and not just for vaccination certificates.

https://techxplore.com/news/2021-12-vaccine-passports-flaws-safer.html

Franco-Austrian firm Valneva's COVID jab under EU review

 Europe's drug watchdog launched an accelerated review Thursday of a COVID-19 vaccine by Franco-Austrian biotech firm Valneva, for which the EU has already signed a deal for up to 60 million doses.

The jab—which uses "inactivated" viruses rather than the new mRNA technology of the Pfizer or Moderna shots—showed in trials that it produced antibodies against coronavirus, the European Medicines Agency (EMA) said.

"EMA's human medicines committee has started a rolling review of VLA2001, a COVID-19 vaccine being developed by Valneva," the Amsterdam-based regulator said in a statement.

"While EMA cannot predict the overall timelines, it should take less time than normal to evaluate an eventual application because of the work done during the rolling review," it said.

It typically takes a few months for vaccines to go from the review stage to approval, although some such as those developed in Russia and China have been waiting longer.

The European Commission announced a deal with Valneva on November 10 to provide about 27 million doses in 2022 and 33 million in 2023.

Valneva's shares rose on that announcement, but have not completely eclipsed their losses from September, when Britain cancelled an order for 100 million doses of the jab, wiping out more than half the stock market valuation.

The Nantes-based firm has received backing from the French government, which was embarrassed by the country's failure to produce a COVID-19 jab following setbacks for national pharma champion Sanofi and the renowned Pasteur Institute.

The EMA said Valneva's studies "suggest that the vaccine triggers the production of antibodies that target SARS-CoV-2, the virus that causes COVID-19, and may help protect against the disease."

"EMA will evaluate data as they become available to decide if the benefits outweigh the risks," it added.

Valneva's jab uses the same inactivated virus method as most flu and many childhood vaccines, which health officials hope could reduce vaccine scepticism about some of the newer-technology jabs.

The EMA has so far approved four vaccines for use for adults in the EU.

The US-German jab by Pfizer-BioNTech and the shot by US pharma firm Moderna use messenger RNA technology. The British-Swedish AstraZeneca-Oxford jab and Johnson & Johnson vaccine use viral vector technology.

A decision on a bid for approval by US pharma firm Novavax is expected within weeks.

https://medicalxpress.com/news/2021-12-franco-austrian-firm-valneva-covid-jab.html

COVID-19 infection can be inhibited by elements of human microbiome

 In the human microbiome, researchers have identified metabolites (intermediate or end products of metabolism) that inhibit COVID-19 infection in cell-based models of the virus. The finding, reported this week in the journal mSphere, an open-access journal of the American Society for Microbiology, is yet another example of the wealth of information that can be gained by studying the human microbiome, the collection of microbes, bacteria, fungi and viruses that live on and inside the human body. The finding may also help in the development of new therapeutics that can battle COVID-19 infections.

"We have found that bacteria that grow on and in you make specific molecules that can inhibit, at least in a laboratory setting, the cell-based viral infection of SARS-CoV-2, and the molecules appear to do that by a number of different mechanisms," said study principal investigator Sean Brady, Ph.D., professor and head of the Laboratory of Genetically Encoded Small Molecules, at the Rockefeller University, New York City.

Brady said the COVID-19 pandemic has highlighted the need to identify additional antiviral small molecules to complement existing therapies. While increasing evidence suggests that metabolites produced by the human microbiome have diverse biological activities affecting the human host, there is comparatively little information on the metabolites' antiviral properties.

In the new study, Brady and colleagues used a cell-based SARS-CoV-2 infection assay to screen metabolites from a sample of bacteria from the human microbiome. They identified 3 bacterial metabolites capable of inhibiting SARS-CoV-2 infection: An adenosine analog, tryptamine and a disubstituted pyrazine.

The identified molecules display structural similarities to synthetic drugs that have been explored for the treatment of COVID-19. "It was intriguing that of all the chemistries available, the metabolites we uncovered from the microbiome all bore similarities to clinically-relevant antivirals," said Frank Piscotta, Ph.D., lead author on the study and a post-doc in the Laboratory of Genetically Encoded Small Molecules.

The researchers say these molecules could serve as starting points for the development of new antivirals. In addition, researchers could deliver the antiviral-producing bacteria as a therapeutic intervention. The researchers say they want to study the mechanisms by which the metabolites function and whether the bacteria producing these molecules have any effect on viral infection upon colonization of an animal. As more data becomes available, they also plan to examine whether the presence or absence of these antiviral-producing bacteria in humans can be linked to severity of viral infection.

"Our discovery of structurally diverse metabolites with anti-SARS-CoV-2 activity from screening a small fraction of the bacteria reported to be associated with the human microbiome suggests that continued exploration of phylogenetically diverse human-associated bacteria is likely to uncover additional small molecules that inhibit SARS-CoV-2 as well as other viral infections," said Brady.

Brady says this is one of the first studies to show that molecules produced by the human microbiome can inhibit viral infections, particularly of coronaviruses like SARS-CoV-2.

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Explore further

COVID-19 testing kits also can measure oral microbiome in saliva

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More information: Frank J. Piscotta et al, Metabolites with SARS-CoV-2 Inhibitory Activity Identified from Human Microbiome Commensals, mSphere (2021). DOI: 10.1128/mSphere.00711-21

https://medicalxpress.com/news/2021-12-covid-infection-inhibited-elements-human.html