Roche Touts Phase II MS Data on Heels of Sanofi’s Late-Stage Stumbles

 

Days after Sanofi reported back-to-back failures for its BTK inhibitor, Roche’s fenebrutinib on Wednesday scored a mid-stage win in relapsing multiple sclerosis, demonstrating near-total elimination of disease activity.

Roche on Wednesday unveiled open-label extension data from its Phase II FENopta study, demonstrating that its investigational BTK inhibitor fenebrutinib elicited “near-complete suppression of disease activity” in patients with relapsing multiple sclerosis.

FENopta’s results showed that T1 gadolinium-enhancing lesions, which are key markers of inflammation, were absent in 99% of patients at 48 weeks after treatment with fenebrutinib. Patients also experienced three times the degree of reduction in the volume of T2 lesions—indicative of chronic disease burden—during the study’s open-label extension (OLE) period than during its double-blind phase.

In terms of safety, fenebrutinib’s adverse event profile during the OLE was consistent with what had been previously reported. The most common side effects were urinary tract infection, COVID-19 and pharyngitis. FENopta OLE detected one asymptomatic case of alanine aminotransferase elevation, which was subsequently resolved after discontinuing fenebrutinib treatment.

“After a year of treatment, our BTK inhibitor was able to suppress nearly all disease activity and disability progression in people with multiple sclerosis,” Roche CMO Levi Garraway said in a statement, noting that if these data are validated and confirmed in late-stage studies, “fenebrutinib could further advance the treatment landscape” for multiple sclerosis (MS).

Roche will present full data from and analyses of FENopta at the upcoming annual congress of the European Committee for Treatment and Research in Multiple Sclerosis, being held in Denmark later this month.

Wednesday’s readout comes after one of Roche’s top MS rivals Sanofi posted back-to-back late-stage flops for its own BTK blocker tolebrutinib. Without providing specific data from the Phase III GEMINI 1 and GEMINI 2 studies, Sanofi revealed on Monday that tolebrutinib was unable to significantly improve annualized relapse rate versus Aubagio (teriflunomide) in patients with relapsing MS.

Meanwhile, Sanofi’s Phase III HERCULES study met its primary endpoint, demonstrating the therapeutic potential of tolebrutinib in non-relapsing secondary progressive multiple sclerosis (nrSPMS). According to Sanofi R&D head Houman Ashrafian, the triple readouts “bring into sharp focus which patient population we should be treating,” suggesting that the pharma could be focusing its tolebrutinib efforts on nrSPMS moving forward—though no definite announcement has yet been made.

Still, such a move would leave an opening for Roche, which is running the Phase III FENhance 1 and FENhance 2 studies assessing fenebrutinib in relapsing MS. The pharma is also evaluating the BTK inhibitor for primary progressive MS in the late-stage FENtrepid trial. Readouts from these studies are expected by the end of 2025.

Designed to be orally available, fenebrutinib is a blocker of the BTK enzyme, which under healthy circumstances helps regulate B cell development and activation, facilitating the activity of innate immune system cells such as macrophages and microglia. By targeting this protein, fenebrutinib can help temper MS disease activity while also slowing disability progression.

In December 2023, the FDA put fenebrutinib’s MS program under partial clinical hold after detecting several cases of liver injury.

https://www.biospace.com/drug-development/roche-touts-phase-ii-ms-data-on-heels-of-sanofis-late-stage-stumbles

Axsome: FDA Accepts NDA Resubmission for Migraine Med

 Axsome Therapeutics, Inc. (NASDAQ: AXSM), a biopharmaceutical company developing and delivering novel therapies for the management of central nervous system (CNS) disorders, today announced that the U.S. Food and Drug Administration (FDA) has acknowledged the resubmission of the Company’s New Drug Application (NDA) for AXS-07 for the acute treatment of migraine. The FDA designated the resubmission as a Class 2 resubmission and set a Prescription Drug User Fee Act (PDUFA) action goal date of January 31, 2025.

https://www.globenewswire.com/news-release/2024/09/04/2940340/33090/en/Axsome-Therapeutics-Announces-FDA-Acceptance-of-NDA-Resubmission-for-AXS-07-for-the-Acute-Treatment-of-Migraine.html

Biogen's Higher Dose Spinraza Shows To Slow Neurodegeneration Faster

 Biogen Inc. (NASDAQ:BIIB) revealed topline data from the pivotal cohort (Part B) of the Phase 2/3 DEVOTE study evaluating the safety and efficacy of a higher dose regimen of nusinersen in treatment-naïve, symptomatic infants with spinal muscular atrophy (SMA).

The investigational higher dose regimen of nusinersen comprises a more rapid loading regimen, two 50 mg doses 14 days apart, and a higher maintenance regimen, 28 mg, every four months, compared to the approved nusinersen 12 mg regimen (Spinraza).

The study met its primary endpoint at six months, achieving a statistically significant improvement in motor function in infants who received the higher dose regimen compared to a prespecified matched sham (untreated) control group from the ENDEAR study.

“The encouraging topline results from DEVOTE show that the higher dose regimen can slow neurodegeneration faster, as shown by greater reductions in neurofilament at day 64 relative to the approved dose. Over time, the higher dose regimen led to meaningful clinical benefit in infants with symptomatic SMA,” said Stephanie Fradette, Head of the Neuromuscular Development Unit at Biogen.

Results favored the higher dose regimen relative to sham across secondary endpoints and trended in favor of the higher dose regimen over the currently approved 12mg regimen on key biomarker and efficacy measures.

The higher dose regimen was generally well tolerated, with reported adverse events generally consistent with SMA and the known safety profile of nusinersen.

Spinraza is approved in more than 71 countries to treat infants, children, and adults with spinal muscular atrophy (SMA).

As a foundation of care in SMA, more than 14,000 individuals have been treated with Spinraza worldwide.

https://finance.yahoo.com/news/biogens-higher-dose-spinraza-shows-144328019.html

'FBI Warns Of North Korean 'Social Engineering' Schemes To Steal Crypto'

 by Turner Wright via CoinTelegraph.com,

The United States Federal Bureau of Investigation (FBI) has issued a warning to employees at digital asset firms regarding the latest attempt by the Democratic People’s Republic of Korea to steal crypto.

In a Sept. 3 notice, the FBI said North Korean malicious cyber actors were targeting workers at decentralized finance and cryptocurrency companies to steal funds through “complex and elaborate” social engineering campaigns. Specifically, the federal agency warned that the scammers had researched firms associated with cryptocurrency-tied exchange-traded funds, or ETFs.

How the scam works

The actors employed schemes, including fake offers of employment or investment opportunities and impersonating well-known individuals associated “with certain technologies” to trick users. The scammers may then provide a link to a “pre-employment test” or another download to install malware.

“The actors usually attempt to initiate prolonged conversations with prospective victims to build rapport and deliver malware in situations that may appear natural and non-alerting,” said the FBI, adding:

“The actors usually communicate with victims in fluent or nearly fluent English and are well versed in the technical aspects of the cryptocurrency field.”

Source: FBI

Since 2017, North Korean hackers have stolen roughly $3 billion in crypto using such schemes. The Lazarus Group, a group of hackers tied to the reclusive nation, has allegedly been responsible for many high-profile attacks targeting crypto users.

The FBI has issued several warnings related to crypto scammers, including those impersonating employees of crypto exchanges and targeting users to compromise their accounts. In June, the federal agency said malicious actors had posed as employees of law firms offering fake crypto recovery services.

https://www.zerohedge.com/technology/fbi-warns-north-korean-social-engineering-schemes-steal-crypto

How Reuters Manipulates The Oil Market, In Two Headlines

 100% of the time, Reuters' oil market manipulation - on behalf of various unnamed deep tate interests - works 100% of the time.

Last Friday morning, just as Brent crude was threatening to extend gains above $80, forcing oil CTAs and other momentum-chasers to close out their near record net short positioning...

... Reuters did what it has done so many times before, and published an oil market manipulating report, designed to crush the price of oil and reverse upward momentum to snuff out the risk of an accelerating short squeeze. As we reported at the time, and with oil just barely above 2024 lows, Reuters cited "six sources who wish to remain anonymous" that OPEC+ is set to proceed with a planned oil output hike from October, because "Libyan outages and pledged cuts by some members to compensate for overproduction counter the impact of sluggish demand" which - as we said - is idiocy as the only thing that matters for oil prices - a bump in Chinese demand - is missing.

Predictably, oil tumbled instantly - a reaction that was naturally welcome by the deep state forces propping up the puppet presidential candidate known as Kamala Harris as it meant even lower gas prices, and  which angered us because as we explained:

... according to Reuters, six OPEC+ sources - who almost certainly are being spoonfed what to tell Reuters by the Deep State which is scrambling to keep gas prices as low as possible ahead of the elections - the plan to increase production remains in place as the loss of Libyan output tightens the market and hopes build that the U.S. Federal Reserve will cut interest rates in mid-September. Which, again, is absolute idiocy, and we expect that OPEC+ will issue an official denial within minutes, especially since Saudi Energy Minister Prince Abdulaziz bin Salman previously said OPEC+ could pause or reverse the production hikes if it decides the market is not strong enough, which it clearly is not right now.

Well, we were wrong: it wasn't minutes, it was a few days... but what is so ridiculous that not even we anticipated that none other than Reuters would report the reversal, discrediting its own credibility but cementing its ability to manipulate the price of oil at will because there are still HFT algos that buy whatever bullshit Reuters has to "report."

This morning, just 4 days after Reuters reported precisely the opposite, the news wire shocked - and we use the term "shocked" very loosely, because it is precisely what we said would happen -  us with the following...

OPEC+ is discussing a delay in a planned output increase next month as oil prices hit their lowest in 9 months, three sources from the producer group told Reuters on Wednesday.

And one wonders why oil prices hit their lowest in 9 months. Would it have something to do with Reuters own reporting guaranteeing that oil prices would hit 9 month lows?

It gets funnier: just as we said, that the Reuters "report" would guarantee a denial from OPEC+ that it was set to restore output, Reuters reported precisely that:

Last week, the group looked set to proceed with a 180,000 barrel per day (bpd) hike in October, but market volatility from oil facility shutdowns in Libya and a weak demand outlook have raised concern within the group, one of the sources said.

Would it be the same source that spoonfed Reuters the fake news that sparked the oil rout, allowing said source to then quickly load up on oil at a 5% discounted price? And the punchline:

There were suggestions to delay the increase, one of the sources said. Another said a delay was looking highly possible.

Of course, any credible media organization would - or rather should - have considered all of this when it reported Friday's market manipulating garbage, but of course it's Reuters, which makes money from sparking volatility in the commodity world, even if it is then forced to refute its own reporting.

So to summarize, what a difference 5 days makes.

To summarize: we are now back to where we were before Reuters' Friday fake news report, but with momentum now crushed, oil is trading at the lowest price of the year, assuring even lower gas prices - however briefly before we hit tank bottoms - ahead of the election, just as the deep state ordered it...

https://www.zerohedge.com/markets/how-reuters-manipulates-oil-market-two-headlines

California Scuttles Reparations Bills As Supporters Denounce A Political Bait-And-Switch

 by Jonathan Turley,

We have previously discussed (here and here and here and here) the push for reparations in California that has been touted by California Gov. Gavin Newsom and Democrats for years. After the Democrats campaigned on the issue in past elections, I wrote a column about how this bill had come due after years of delay for study and recommendations.

The legislature, however, just stamped the bill “return to sender” and shelved the two reparations bills with the reported support of Newsom.

The reaction is not surprising that there has been a bait-and-switch by Democrats on the issue.

Last week, the California legislature did approve proposals allowing for the return of land or compensation to families whose property was unjustly seized by the government, and issuing a formal apology for laws and practices that have harmed Black people. However, the two bills to establish a fund for reparation payments – Senate Bills 1403 and 1331 – were tabled.

State Sen. Steven Bradford blamed Democratic California Gov. Gavin Newsom for the result, stating that the governor made clear that he would veto them.

Newsom signed a $297.9 billion budget in June that included up to $12 million for reparations legislation. However, that is a drop in the bucket given the billions demanded and it is not clear how the money will be spent.

Adding to the anger is the fact that the legislature approved a bill to allow undocumented persons to receive no-interest loans of up to $150,000 to cover down payments on new homes.

It is now unclear what will happen next, though sponsors are saying that they will continue to push for legislation green lighting reparation payments.

Some congressional Democrats have pushed for similar federal reparations and passed a bill out of the House Judiciary Committee in 2021 that failed to receive a floor vote.

BET founder Robert Johnson has called for $14 trillion in federal reparations.

As discussed earlier, there are a host of legal and practical questions over the reparation payments that will have to be resolved. Even with passage, the bills would likely face constitutional challenges.

https://www.zerohedge.com/political/california-scuttles-reparations-bills-supporters-denounce-political-bait-and-switch

First Dollar General, Now Dollar Tree Plunge As Both Warn Of Core Customer Under Pressure

 Shares of Dollar Tree plunged nearly 12% in premarket trading in New York after the discount retailer, which operates thousands of stores nationwide, posted fiscal second-quarter earnings that fell short of Wall Street expectations. The company also slashed its full-year outlook, pointing to mounting financial pressures on middle-income and higher-income customers. This comes less than a week after major rival Dollar General reported a "financially constrained core customer" that sent shares crashing the most on record.

Dollar Tree reported this morning that the macroeconomic environment is pressuring its middle—and higher-income consumers. Traffic increased during the quarter, but the average ticket size decreased. It said second-quarter comparable sales and adjusted earnings per share missed Wall Street's expectations. 

Here's a snapshot of second-quarter earnings (courtesy of Bloomberg): 

• Adjusted EPS 67c vs. 91c y/y, estimate $1.05
• EPS 62c vs. 91c y/y

Enterprise comparable sales +0.7% vs. +6.9% y/y, estimate +1.45%

• Family Dollar comparable sales -0.1%, estimate -0.21%
• Dollar Tree Segment comparable sales +1.3% vs. +7.8% y/y, estimate +2.89%

Net sales $7.37 billion, +0.7% y/y

• Dollar Tree net sales $4.07 billion, +5% y/y, estimate $4.16 billion
• Family Dollar net sales $3.31 billion, -4% y/y, estimate $3.35 billion

Gross profit margin 30% vs. 29.2% y/y, estimate 29.9%

• Dollar Tree gross margin 34.2% vs. 33.4% y/y, estimate 34.1%
• Family Dollar gross margin 24.9%, estimate 24.6%

Total location count 16,388, -0.5% y/y, estimate 16,374

• Dollar Tree Locations 8,627, +5.5% y/y, estimate 8,294
• Family Dollar locations 7,761, -6.5% y/y, estimate 8,071

With nearly 16,400 stores nationwide, the discount retailer now expects its full-year consolidated net sales outlook between $30.6 billion and $30.9 billion versus the previous forecast of $31 billion to $32 billion. 

• Sees net sales of $30.6 billion to $30.9 billion, saw $31.0 billion to $32.0 billion
• Sees adjusted EPS $5.20 to $5.60, estimate $6.57 (Bloomberg Consensus)

Chief Financial Officer Jeff Davis wrote in a statement that the "increasing effect of macro pressures on the purchasing behavior of Dollar Tree's middle- and higher-income customers" was the main driver in slashing its full-year sales forecast. 

Here's Goldman's Eric Mihelc and Scott Feiler's take on Dollar Tree earnings:

"DLTR -13%...Low bar post DG results but the 20% guidance cut is worse than expected (a cut was expected but most we had heard from were not this low). Also, they spoke to weakness spreading to their middle and higher income (it's all relative) customers.  Details: 2Q EPS of $0.97 vs Consensus $1.04, with revenues 160 bps light. Comps of +0.7% vs Consensus +1.6%. Dollar Tree brand drove the comp miss. SG&A also missed by 200 bps. They spoke to the increasing effect of macro pressures on the purchasing behavior of Dollar Tree's middle- and higher-income customers. Guides 3Q EOS light at $1.10 (mid) vs Consensus $1.32 and revenues 1% light. Lowers 2024 EPS to $5.40 (mid) vs prior $6.75, a 20% cut, on a revenue cut as well." 

What's critical to note for the political strategist: Dollar Tree & Family Dollar and Dollar General stores are mostly concentrated in the eastern half of the US. Mangment's gloom about its core customer base should serve as a proxy for consumer sentiment for mid/low-tier consumers. In other words, there is a lot of gloom and doom among working-poor Americans in critical swing states.

Last week, Dollar General shares crashed the most on record after management warned that core customers "feel financially constrained."

DG's stores are primarily based in the eastern half of the US. Again, this should serve as a proxy for consumer sentiment.

In markets, shares of Dollar Tree in New York plunged 12%. 

Is the slide in Dollar Tree and Dollar General shares a signal for broader main equity indexes?

Meanwhile, both discount retailers are facing heightened competition from Aldi and Walmart as corporate America fights over the market share of the middle class that is imploding under Bidenomics. 

https://www.zerohedge.com/markets/first-dollar-general-now-dollar-tree-shares-plunge-both-discount-retailers-warn-core