FDA rejects Gilead’s hepatitis D therapy Hepcludex

 Gilead Sciences has been knocked back in its quest to bring the first drug therapy for hepatitis D virus (HDV) to the US market, after the FDA rejected its marketing application.

News of the complete response letter (CRL) for bulevirtide, which is already on sale in other markets around the world, including Europe, as Hepcludex, came in remarks by Gilead’s chief medical officer Merdad Parsey in the company’s third-quarter results call.

Parsey said the FDA has concerns about the “manufacture and delivery” of Hepcludex but has not asked for new safety or efficacy clinical trials of the drug. “We plan to resubmit as quickly as possible, and we’ll work with the agency on the path forward,” he added.

HDV is unusual in that it exists only as a co-infection with hepatitis B virus (HBV) and occurs in around 5% of the estimated 257 million people around the world who are chronically infected with HBV – around 12 million people.

Infection is serious, however, as having both HBV and HDV increases the risk of liver disease-related death and liver cancer, and current treatment with pegylated interferon alpha products – which takes 48 weeks to complete – isn’t very effective.

Like HBV, HDV is most commonly transmitted from mother to child during birth, and through contact with blood or other body fluids, for example, through sex with an infected partner or the sharing of syringes.

For that reason, Gilead combines its HBV/HDV sales figures in financial updates, reporting a 7% increase in the third quarter to $264 million driven mainly by continued growth for HBV-suppressing drug Vemlidy (tenofovir alafenamide). Hepcludex features in the ‘other HBV/HDV’ category in its updates, which contributed $14 million in the period.

Gilead’s FDA filing for Hepcludex was made on the back of clinical trials, which showed that treatment with the drug led to significant HDV RNA declines and improvements in liver damage biomarkers at 24 weeks.

The disappointment came as Gilead reported strong sales growth across its hepatitis, HIV and oncology categories that drove product sales up 11% to $6.1 billion – albeit excluding blockbuster COVID-19 antiviral Veklury which plunged 52% to $925 million on lower coronavirus hospitalisation rates.

HIV sales rose 7% to $4.5 billion, but the biggest growth came in Gilead’s oncology business, which shot up 79% to $578 million, driven mainly by Trodelvy (sacituzumab govitecan) in both second- and third-line settings for the treatment of metastatic triple-negative breast cancer (TNBC).

https://pharmaphorum.com/news/fda-rejects-gileads-hepatitis-d-therapy-hepcludex/

Nuvalent: Prelim Phase 1 Lung Cancer Data

 Favorable preliminary safety profile of NVL-520 suggests potential for a highly ROS1-selective, TRK

sparing design, with no dose-limiting toxicities, treatment-related serious adverse events, treatment-
related dizziness, or adverse events leading to treatment reductions or discontinuations as of the
data cut-off date

Encouraging preliminary signs of activity observed across all dose levels in heavily pre-treated
patients with ROS1-positive NSCLC, including in subgroups of patients with G2032R resistance
mutation or with brain metastases

Company to host conference call today at 8:30 am EDT

Nuvalent will host a live webcast and conference call today at 8:30am EDT to discuss these results. The event is accessible through the "Events" section of the Investors page of www.nuvalent.com or by dialing (866) 652-5200 (domestic) or (412) 317-6060 (international) and referring to conference ID 10171503. A replay and accompanying slides will be archived on the Nuvalent website for 30 days.

https://finance.yahoo.com/news/nuvalent-reports-preliminary-phase-1-040100476.html

DaVita outlook cut, conference call info

 Outlook:

The following forward-looking measures and the underlying assumptions involve significant known and unknown risks and uncertainties, including those described below, and actual results may vary materially from these forward-looking measures. For example, the widespread impact of the COVID-19 pandemic continues to generate significant risk and uncertainty, and as a result, our future results could vary materially from the guidance provided below. We do not provide guidance for operating income or diluted net income per share attributable to DaVita Inc. on a basis consistent with United States generally accepted accounting principles (GAAP) nor a reconciliation of forward-looking non-GAAP financial measures to the most directly comparable GAAP financial measures on a forward-looking basis because we are unable to predict certain items contained in the GAAP measures without unreasonable efforts. These non-GAAP financial measures do not include certain items, including capacity closure charges and foreign currency fluctuations, which may be significant. The guidance for our effective income tax rate on adjusted income attributable to DaVita Inc. also excludes the amount of third-party owners' income and related taxes attributable to non-tax paying entities.

	Current 2022 guidance				Prior 2022 guidance
	Low		High		Low		High
	(dollars in millions, except per share data)
Adjusted operating income	$1,375		$1,450		$1,525		$1,675
Adjusted diluted net income per share attributable to DaVita Inc.	$6.20		$6.70		$7.50		$8.50
Free cash flow	$800		$1,000		$850		$1,100

Key drivers of 2023 adjusted operating income growth(1):

(dollars in millions)
Absence of ballot initiative expenses	$60
Integrated Kidney Care	($25) - $0
Treatment volume growth	($200) - $0
Revenue per treatment growth	$200 - $250
Labor pressure and inflation	($300) - ($250)
Cost savings initiatives	$125 - $175
2023 Adjusted operating income growth	($50) - $150

_____________________
(1)	Adjusted operating income growth outlook relative to 2022 adjusted operating income outlook, excluding certain items in both periods.

We will be holding a conference call to discuss our results for the third quarter ended September 30, 2022, on October 28, 2022, at 8:30 a.m. Eastern Time. To join the conference call, please dial (877) 918-6630 from the U.S. or (517) 308-9042 from outside the U.S., and provide the operator the password 'Earnings'. This call is being webcast and can be accessed at the DaVita Investor Relations website investors.davita.com. A replay of the conference call will also be available at investors.davita.com for the following 30 days.

https://finance.yahoo.com/news/davita-inc-3rd-quarter-2022-103000296.html

Study confirms link between COVID-19 vaccination and temporary increase in menstrual cycle length

 A large international study has confirmed the findings of a previous U.S. study that linked COVID-19 vaccination with an average increase in menstrual cycle length of less than one day. The increase was not associated with any change in the number of days of menses (days of bleeding). Funded by the National Institutes of Health, the new study included data from nearly 20,000 people from Canada, the United Kingdom, the United States, Europe and other parts of the world who received any of nine different vaccines. For most study participants, the increase resolved in the cycle following vaccination.

The study’s principal investigator was Alison Edelman, M.D., M.P.H., of Oregon Health & Science University in Portland. It appears in the BMJ Medicine.

https://www.nih.gov/news-events/news-releases/study-confirms-link-between-covid-19-vaccination-temporary-increase-menstrual-cycle-length

Biogen Alzheimer's drug linked to patient death

 

Biogen (NASDAQ:BIIB) shares dropped in the pre-market trading Friday after Stat News reported that the investigational Alzheimer's therapy

https://seekingalpha.com/news/3897190-biib-stock-slips-amid-reports-of-death-linked-to-new-alzheimers-drug

US Accelerates Upgraded Nuke Delivery To Jittery European Allies: Cable

 On the same day that Russia hailed completion of its 'successful' annual nuclear drills, Politico published a bombshell report describing that the US has accelerated plans to maintain upgraded nuclear weapons in Europe. 

Specifically, US defense officials informed NATO allies earlier this month that Europe will host a B61-12 air-dropped gravity bomb, to be transferred by December. Politico reported Wednesday that a classified cable it has seen confirmed this. 

The upgraded bomb was expected to arrive in Europe next spring, but the timeline was accelerated amid Russia's growing nuclear rhetoric surrounding the war in Ukraine. President Biden recently raised eyebrows in saying nuclear "armageddon" is a real possibility for the first time since the close of the Cold War. 

On an official level the Pentagon is disputing that its planned nuclear upgrade for NATO's Europe arsenal is in any way connected to events in Ukraine, however, Politico cites the following sources: 

Two people familiar with the issue of the upcoming shipment to Europe confirmed the accelerated timeframe reported in the diplomatic cable. They asked not to be named due to the sensitivity of the issue.

The cable, which has not previously been made public and was written to be distributed throughout the Pentagon and State Department to give policymakers a rundown of what was discussed among defense ministers at the NATO meeting, clearly indicates that allies are jittery.

The document says that during the meetings, 15 NATO allies raised concerns that the alliance “must not give in to Putin’s nuclear blackmail.”

 

The cable is further quoted by Politico as follows: "Given the rising volume and scale of Russia’s nuclear rhetoric, a subset of allies requested continued consultations at NATO to ensure continued readiness and consistent messaging."

Some analysts cited in the report say the White House is fundamentally sending a message of reassurance to NATO at a moment European countries are feeling "vulnerable", and that the intent is not to escalate nuclear tensions with Moscow: 

“My guess is it is aimed more towards NATO than Russia,” said Tom Collina, director of policy at the Ploughshares Fund, a disarmament group. “There are [older] B61s already there. The Russians know that. They work just fine. The new ones will be newer, but it’s not really that much of a difference. But it may be a way to assure the allies when they are feeling particularly threatened by Russia.”

The upgraded B61-12 is designed to allow the bomb to be carried by a fuller array of US and allied bombers and fighter jets, while older versions had more limited delivery options. The upgraded version is also said to be more accurate. 

The B61 nuclear gravity bomb is deployed at a number of US Air Force and NATO military bases and has almost five decades of service, making it the oldest bomb in the US stockpile. Numerous programs have modified the B61 for safety, security, and reliability since it entered service in the late 1960s, including four B61 variants.

The upgraded B61-12 LEP - a project years in the making, will replace all of the bomb’s nuclear and non‐nuclear components for another two decades, and improve the bomb’s safety, effectiveness, and security. This life extension program will address all age-related issues of the weapon, and enhance its reliability, field maintenance, safety, and use control.

https://www.zerohedge.com/military/us-accelerates-upgraded-nuke-delivery-jittery-european-allies-cable

Macron Admits Half The Crimes In Paris Are Committed By Foreigners

 by John Cody via Remix News,

...but Macron is still pushing for more mass immigration despite data showing the tremendous crime rate of foreign nationals

French President Emmanuel Macron admits that half the crimes committed in Paris are the work of foreigners during an interview yesterday on the France 2 television channel.

“Yes, when we look at delinquency in Paris, we can see that half of the delinquent acts come from foreigners in an irregular situation or awaiting asylum approval,” said Macron.

However, Macron also said that despite the issue with immigration and insecurity, he sees no “existential” link between the two.

“I will never make an existential link between immigration and insecurity,” said Macron just 10 days after the murder of 12-year-old Lola, who was raped, had her throat slashed, and was stuffed in a suitcase by an Algerian migrant who was in the country illegally.

Macron is under severe pressure after the murder, with a number of leading opposition politicians laying the blame for the murder at his feet and pointing to his abysmal record on deportations. Macron previously promised in 2020 that he was aiming for a 100 percent deportation rate. That rate currently hovers under 6 percent, and in the case of Algerians, it is 0.2 percent.

Despite growing anger, Macron is pushing a plan to send more migrants to the countryside, a move that is overwhelming rejected by the French public there. He also said in February of this year that migration from Africa and the Middle East “can make France greater.”

On top of inflation and growing unrest, the issue of immigration is turning political opinion against the French leader. As in the past, such as following the beheading of French history teacher Samuel Paty by a Chechen Islamist teen, Macron has put forward a number of “reforms” to assuage public anger, but many of the proposals were never enforced or have done little to disrupt France’s issues with insecurity, including a 91 percent increase in murders since 2000.

This time around, Macron claims he wants “in-depth reform” and a “debate in parliament on immigration.”

“We must reform our laws in depth to be able to better welcome those we want to welcome,” he said during the Europe 2 interview. He offered little in terms of how he plans to address problems with integration and the country’s inability to deport cirminal migrants.

However, Macron’s admission that illegal migrants or migrants awaiting asylum are responsible for half the crime in Paris is supported by data. The recently retired Paris chief of police, Didier Lallement, made assertions just this month, writing in his new book that “one out of every two crimes is committed by a foreigner, who are often in the country illegally… It is clear that some of the newcomers are integrating through delinquency.”

It is also unclear what the racial and ethnic breakdown of crime statistics is in France, as there are many French citizens of “foreign origin” who are not counted as foreigners since they have obtained citizenship. France does not keep data on the ethnic or racial identity of suspects. However, in other cities, such as Marseilles, 55 percent of all crimes are committed by foreigners, a rate even higher than Paris, illustrating that it is a countrywide issue.

https://www.zerohedge.com/geopolitical/macron-admits-half-crimes-paris-are-committed-foreigners