'United, Delta, Lufthansa, British Airways & Others Cancel Flights To Tel Aviv On War Fears'

 The Lufthansa Group is the latest major airline to cancel all passenger and cargo flights to and from Tel Aviv with immediate effect, following a string of others including United Airlines, Delta, and British Airways, along with Fly Dubai and Brussels Airlines and more.

They are citing security concerns related to Israel's ratcheting war with Hezbollah, as well as soaring tensions resulting from the Wednesday Israel assassination of Ismail Haniyeh in Tehran, which threatens to kick off a broader regional war. The Israeli population remains on edge given that Tehran could launch another direct ballistic missile and drone attack.

A media statement from United explained, "Beginning with this evening’s flight from Newark Liberty to Tel Aviv, we are suspending for security reasons our daily Tel Aviv service as we evaluate our next steps."

"We continue to closely monitor the situation and will make decisions on resuming service with a focus on the safety of our customers and crews," a written statement to media outlets underscored.

Most of the airlines are suspending service tentatively for at least two days or more, with Delta canceling flights between New York's JFK and Tel Aviv through at least Aug.2. However Lufthansa is canceling all the way through August 8. The German airline said, "The reason for this is the current development in the region," according to a spokesperson.

The announcement was issued synonymous with reports of a Lufthansa pilot refusing to land in Israel while still in mid-flight, according to regional sources:

A Lufthansa flight captain refused to land in Israel on Thursday amid rising tensions between Israel and Lebanese group, Hezbollah, according to Israeli media, Anadolu Agency reports.

The flight was scheduled to land at Ben Gurion Airport near Tel Aviv from Munich, Germany, but the captain refused, citing that his crew were not prepared to fly to Israel, the Israeli public broadcaster, KAN, said.

Instead, the flight landed at Larnaca Airport in the Greek Cypriot Administration.

The airline initially informed passengers that the plane would land in the Greek Cypriot Administration for “technical reasons” and then it would be decided whether the flight would continue to Tel Aviv.

Broadly, a number of governments have issued their highest security alerts possible for travel to Lebanon, declaring the country as well as the Palestinian territories a 'do not travel' zone.

A US Embassy-Beirut statement has urged, "Do Not Travel to Lebanon due to rising tensions between Hezbollah and Israel. If you are in Lebanon, be prepared to shelter in place should the situation deteriorate."

The Biden administration has been warning that a major Israel-Lebanon war could break out at any moment, centered on paramilitary group Hezbollah in the south. But at this point, an evacuation of citizens has not yet commenced.

https://www.zerohedge.com/geopolitical/united-delta-lufthansa-others-cancel-flights-tel-aviv-war-fears

Novo Loses IRA Case as NJ Judge Asserts Price Negotiations Are Voluntary

 

Reiterating his ruling in a prior Inflation Reduction Act case, New Jersey District Court Judge Zahid Quraishi ruled that Novo Nordisk’s participation in the Medicare Drug Price Negotiation Program is of its own free will.

A federal judge on Wednesday handed Novo Nordisk a legal loss in its challenge to the Inflation Reduction Act, ruling that its participation in the Medicare Drug Price Negotiation Program is voluntary.

New Jersey District Court Judge Zahid Quraishi referenced his previous ruling on Bristol Myers Squibb and Johnson & Johnson’s challenge to the negotiation program. The two companies in April 2024 lost their respective suits, with Quraishi rejecting their claims that the government is unlawfully setting prices for their products.

“The Court addressed nearly identical constitutional challenges that the Plaintiffs make here,” the judge wrote, reiterating that the Inflation Reduction Act (IRA) program “is neither a physical taking nor a per se taking of a manufacturer’s drugs.” The drug price negotiations also remain voluntary, Quraishi contended, and that pharma companies have “alternative options” if they decide to not participate in the program.

Quraishi also rejected Novo’s arguments invoking its right to freedom of speech under the First Amendment. “The IRA regulates conduct, not speech,” the judge wrote, pointing out that any effects that the program might have on speech “are merely incidental mechanisms used during the price-setting process.”

Novo first sued the Biden administration over its IRA program in September 2023, alleging that the drug price negotiations violate the Constitution “because it eliminates essential procedural and substantive safeguards” to “protect the important public and private interests at stake when price controls are imposed on a major sector of the economy.”

The Centers for Medicare and Medicaid Services (CMS) also “sought to impose new substantive obligations that far exceed the lawful bounds” of its authority, according to Novo.

In December 2023, Novo filed a motion for summary judgement in the case. A month later, the government registered its opposition to Novo’s motion and filed its own cross-motion for summary judgement in its favor. Quraishi on Wednesday granted its cross-motion and denied Novo’s original summary judgement motion.

The pharma industry has so far been unsuccessful in its legal challenge to the IRA. In October 2023, Judge Michael Newman of the Southern District of Ohio blocked the U.S. Chamber of Commerce’s request for a preliminary injunction against the Medicare Drug Price Negotiation Program.

In March 2024, AstraZeneca also lost its lawsuit with a Delaware federal judge finding that the pharma has “no legitimate claim of entitlement to sell its drugs to the Government at any price other than what the Government is willing to pay.”

The price negotiations with participating companies for the initial 10 drugs in the program wrapped up this week, and CMS is due to publish the maximum fair prices in September. The new prices will take effect in 2026.

https://www.biospace.com/policy/novo-loses-ira-case-as-nj-judge-asserts-price-negotiations-are-voluntary

Sanofi Sues Sarepta Over Elevidys DMD Gene Therapy, Alleges Patent Infringement

 

Sarepta has been hit with another patent infringement lawsuit, this time from Sanofi and its subsidiary Genzyme alleging that the biotech used protected technology related to AAV vectors.

Sanofi’s subsidiary Genzyme is suing Sarepta Therapeutics, alleging that by producing and marketing the Duchenne muscular dystrophy gene therapy Elevidys (delandistrogene moxeparvovec-rokl), the biotech is infringing on the pharma’s protected technologies.

Sanofi’s lawsuit claims that Elevidys violates two of its patents—dubbed the 542 and 721 patents—which are related to the composition and production of adeno-associated virus (AAV) vectors, which are used to package the actual therapeutic gene construct for delivery into the body. Both are set to expire on June 1, 2025.

The patents pertain to specific methods of preparing “high ionic strength compositions” in which AAV vectors “do not significantly aggregate” when stored, according to the lawsuit. Elevidys, Sanofi alleges, is contained in a solution that makes use of this patent-protected formulation, allowing the gene therapy to be kept without clumping, which would otherwise compromise its final quality and use.

Sanofi is seeking a trial by jury and damages “adequate to compensate” the pharma for the alleged infringement. If it succeeds, Sanofi could also win “increased damages” of up to three times the amount assessed, along with pre-judgement and post-judgement interests and costs.

The lawsuit follows a Delaware judge’s decision in January 2024 ruling in favor of the biotech in a separate patent row with Regenxbio and the University of Pennsylvania. According to Reuters, U.S. District Judge Richard Andrews dismissed the challenge to Sarepta’s Elevidys, finding no evidence that the gene therapy violated the plaintiffs’ protected technologies.

By delivering a functioning copy of the dystrophin gene, Elevidys addresses the underlying cause of Duchenne muscular dystrophy (DMD), helping restore function and strength to muscles that would otherwise have been ravaged by the disease.

The FDA granted Elevidys accelerated approval in June 2023, opening up its use in ambulatory patients four to five years of age. In June 2024, the regulator awarded Elevidys full approval and broadened its target population to include patients who are at least four years old, regardless of ambulation status. Only those with a mutation in the DMD gene can receive the therapy.

Elevidys got the full approval despite failing its confirmatory Phase III trial. In October 2023, the biotech released results from the EMBARK study showing that Elevidys was unable to significantly improve functional mobility versus placebo. Nevertheless, Sarepta zoomed in on key secondary endpoints, arguing at the time that Elevidys yielded “robust evidence” of “clinically meaningful treatment benefit” in patients.

https://www.biospace.com/business/sanofi-sues-sarepta-over-elevidys-dmd-gene-therapy-alleges-patent-infringement

Lilly’s Tirzepatide Clears Phase III Cardiovascular Study on Heels of Novo

Eli Lilly on Thursday released late-stage data showing a 38% reduction in the risk of heart failure outcomes, as it plays catch-up with Novo Nordisk’s semaglutide which won the FDA’s cardio nod in March.

Eli Lilly’s blockbuster weight-loss treatment tirzepatide aced the Phase III SUMMIT study, demonstrating significant therapeutic benefit in patients with heart failure with preserved ejection fraction, according to a topline readout on Thursday.

At a median follow-up of 104 weeks, patients treated with tirzepatide versus placebo saw a 38% drop in the relative risk of heart failure outcomes, as quantified by the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score. The treatment effect was statistically significant, with a p-value of 0.026, according to Lilly.

SUMMIT defined heart failure outcomes as a composite of cardiovascular death and urgent healthcare visits and hospitalizations related to heart failure, as well as the intensification of oral diuretic medication.

Tirzepatide also met SUMMIT’s key secondary endpoints, leading to an improvement in exercise capacity and a reduction in the inflammatory marker high-sensitivity C-reactive protein. Mean body weight declined through 52 weeks of treatment, with tirzepatide-treated patients losing 15.7% of their body weight compared to 2.2% in the placebo group.

SUMMIT is a randomized, double-blinded, parallel and placebo-controlled study that assessed three doses of tirzepatide—5 mg, 10 mg and 15 mg. The trial enrolled more than 730 obese adults with heart failure with preserved ejection fraction (HFpEF), with or without type 2 diabetes. In addition to efficacy, SUMMIT also evaluated the safety and tolerability of tirzepatide in this indication.

The most commonly reported side effects in SUMMIT were related to the gastrointestinal system—such as nausea, vomiting, constipation and diarrhea—though most were mild or moderate in severity. The study found no new signals of concern. Tirzepatide’s safety profile was consistent with what previous studies have found.

Jeff Emmick, senior vice president of product development at Lilly, in a statement called SUMMIT a “first-of-its-kind trial” showing that tirzepatide “reduced severity of symptoms and improved heart failure outcomes” in HFpEF patients with obesity. Previous studies on incretin-based treatments “focused on symptoms and physical limitations,” according to Emmick.

Lilly will continue its analysis of SUMMIT’s findings, which it plans to present at an upcoming scientific conference and submit to a peer-reviewed journal. The pharma will also share these results with the FDA to seek a cardiovascular approval for tirzepatide “starting later this year,” according to its announcement.

Wednesday’s results come as Lilly plays catch-up with Novo Nordisk, whose blockbuster GLP-1 therapy Wegovy (semaglutide) won the FDA’s nod in March 2024 to reduce the risk of cardiovascular death, heart attack and stroke in obese or overweight adults with cardiovascular diseases.

Novo is also studying the potential of semaglutide in renal diseases. In March 2024, the Danish drugmaker released findings from the Phase III FLOW study, touting a 24% reduction in the risk of kidney disease progression, major adverse cardiovascular events and kidney death in type 2 diabetes patients with chronic kidney disease.

Meanwhile, Lilly is trying to expand tirzepatide into metabolic dysfunction-associated steatohepatitis (MASH) and sleep apnea. The pharma posted Phase II data in June 2024, demonstrating the absence of MASH without fibrosis worsening in at least 50% of patients. That same month, Lilly unveiled findings from the Phase III SURMOUNT-OSA program, which showed that tirzepatide could cut the apnea-hypopnea index by up to nearly 63%.

https://www.biospace.com/drug-development/lillys-tirzepatide-clears-phase-iii-cardiovascular-study-on-heels-of-novo

FDA Questions Evidence Backing Zevra’s Rare Disease Therapy Pre Adcomm

 

The Genetic Metabolic Diseases Advisory Committee will meet on Friday to discuss Zevra’s modified scale to describe the efficacy of its drug candidate for the treatment of Niemann-Pick disease type C.

Ahead of Friday’s advisory committee meeting, the FDA has raised concerns about Zevra Therapeutics’ investigational oral drug arimoclomol, which the biotech is proposing for the treatment of Niemann-Pick disease type C.

The regulator’s internal reviewers flagged “uncertainties” in Zevra’s efficacy assessment for arimoclomol, particularly the use of a rescored NPC Clinical Severity Scale (NPCCSS) to evaluate treatment effect. The FDA also raised questions regarding additional clinical and non-clinical data as confirmatory evidence for arimoclomol’s benefit.

“A drug’s effectiveness must be established by substantial evidence,” the FDA’s staffers wrote in its briefing document, adding that this requirement has typically been satisfied by two “adequate and well-controlled clinical investigations to establish effectiveness.”

However, in some cases, the regulator can consider data from just one study—plus confirmatory evidence—provided that these findings “are sufficient to establish effectiveness.” Companies focused the rare diseases market, where enrollment presents a significant challenge and where it is infeasible to run multiple trials, typically prefer this approach.

Zevra chose to use this pathway for arimoclomol by presenting data from the NPC-002 trial, a 12-month, randomized, placebo-controlled and double-blinded study. In the biotech’s original application, it used the 12-month change in the NPCCSS score which measured disease activity according to five domains: swallowing, speech, fine motor, ambulatory and cognitive function.

In June 2021, the FDA rejected arimoclomol citing “concerns with the interpretability” with the five-domain NPCCSS score, especially in its swallow and cognition scales, according to Wednesday’s briefing document. The regulator also flagged the “weak and contradictory confirmatory evidence of effectiveness” for arimoclomol.

In its resubmission, Zevra employed a rescored four-domain NPCCSS tool which did away with the cognition domain and used a modified swallow domain. The FDA is asking the newly formed Genetic Metabolic Diseases Advisory Committee on Friday to determine whether Zevra’s reanalysis was adequate. The regulator is also asking the panel of external experts to review the totality of evidence and decide whether this supports the efficacy of arimoclomol.

Nieman-Pick disease type C (NPC) is an ultra-rare neurodegenerative disorder that manifests as severe cognitive and physical impairments, affecting speech, motor and swallowing functions. The disease is caused by mutations in the NPC1 or NPC2 genes, which affect the clearance and transport of cholesterol and other lipids inside the cell, leading to the toxic accumulation of these compounds in various organs such as the brain.

Arimoclomol seeks to addresses a central disease pathway in NPC by crossing the blood-brain barrier and helping cells resist stress, preventing their destruction despite lipid build-up.

https://www.biospace.com/fda/fda-questions-strength-of-evidence-backing-zevras-rare-disease-therapy-ahead-of-adcomm

CareDx ups revenue guidance

 Second Quarter 2024 Financial Highlights

• Reported total revenue of $92.3 million, an increase of 31% year-over-year.
• Grew Testing Services volume to 43,700 tests, an increase of 17% year-over-year.
• Reported GAAP net loss of $1.4 million, non-GAAP net income of $13.6 million, and positive adjusted EBITDA of $12.9 million, a significant improvement from the second quarter 2023.
• Generated $18.9 million cash from operations. Ended the quarter with cash, cash equivalents, and marketable securities of approximately $228.9 million, with no debt.
• Raised 2024 guidance for annual revenue to $320 to $328 million and adjusted EBITDA to a gain of $9 to $15 million.

https://www.businesswire.com/news/home/20240731876395/en/

Biomea Fusion Q2 update

 DIABETES

COVALENT-111 (BMF-219 for Type 2 Diabetes) & COVALENT-112 (BMF-219 for Type 1 Diabetes)

• On June 6, 2024, company announced it received notice from FDA that a full clinical hold has been placed on Biomea’s ongoing Phase I/II clinical trials of the company’s investigational covalent menin inhibitor BMF-219 in type 2 and type 1 diabetes (COVALENT-111 and COVALENT-112), respectively. In its communication, FDA noted deficiencies based on the level of possible drug-induced hepatotoxicity observed in the completed dose escalation phase of COVALENT-111.
• Initial data reported from the first two type 1 diabetes patients dosed with BMF-219 in COVALENT-112 demonstrated early signs of clinical activity with improved measures of beta-cell function after initial treatment with BMF-219. BMF-219 has been generally well tolerated by both patients.

Anticipated Milestones:

• Topline Week 26 data readout of Phase 2b with approximately 195 patients of COVALENT-111 expected for Q4 2024.
• Topline data readout of Phase 2a of COVALENT-112 with approximately 20 patients expected for Q4 2024.

OBESITY

Third Program (Oral, Small Molecule, GLP-1R Agonist)

Anticipated Milestones:

• Announce a third development candidate, a potent, selective, GLP-1 receptor agonist, expected in Q3 2024.
  

ONCOLOGY

COVALENT-101 (BMF-219 for Liquid Tumors)

Anticipated Milestones:

• Complete dose escalation portion of COVALENT-101 expected by year end 2024.
  (Two cohorts, CLL and DLBCL of COVALENT-101 have been discontinued due to insufficient enrollment.)
  

COVALENT-102 (BMF-219 for Solid Tumors)

Anticipated Milestones:

• Complete dose escalation portion of COVALENT-102 expected by year end 2024.
  

COVALENT-103 (BMF-500 for Acute Leukemias)

Anticipated Milestones:

• Complete dose escalation portion of COVALENT-103 expected by year end 2024.

https://www.globenewswire.com/news-release/2024/07/31/2922242/0/en/Biomea-Fusion-Reports-Second-Quarter-2024-Financial-Results-and-Corporate-Highlights.html