Qatar has announced Israel has agreed to the major ceasefire proposal which has been worked on intensely for over the past week. Qatar has also said Hamas has issued 'positive conformation', according to Al Jazeera.
Oil plunged on the news, and amid the first hopeful sign in months that Gaza could witness a breakthrough ceasefire...
FDA Commissioner Robert Califf on Wednesday said the regulator is looking to make improvements to the agency’s advisory committee system made up of nearly 50 panels of external experts.
Speaking on a webinar hosted by the Alliance for a Stronger FDA, Califf said that improving its advisory committees is a “special project” for the regulator’s Chief Scientist Namandjé Bumpus, whose office is working on “systemic” changes to improve the adcomm process.
While Califf provided few details on how Bumpus proposes to optimize the adcomm process, he indicated that the team is finalizing these reforms given the important role these panels of outside experts play in the drug review process.
“We’ve done a lot of work on the advisory committees behind the scenes and work with the centers who each have had their own systems for advisory committees. And I think if you look right now, you’ll see the advisory committees are working better, that is, we’re getting better experts,” Califf said. “This is complicated because of conflict of interest and navigating, getting the right people who actually know the field and can help the FDA with good advice.”
Though Califf said that a vote does not need to be held in most adcomm meetings, there are some places where it is “crucial and helpful.” The FDA chief maintains that the agency is “very dependent on external input” and is critical to the regulator’s reviews.
In an August 2023 Alliance for a Stronger FDA webinar, Bumpus said she wants to streamline the adcomm process to ensure the agency continues to get the expertise it needs from its panels as works to identify the right experts and the most effective way to engage them.
When it comes to the FDA’s fiscal year 2024 budget, Califf on Wednesday said the federal government is on a continuing resolution through March 1 and while the budgetary uncertainty can be “excruciating” the agency’s staff has been through the funding process in previous years.
“The way it looks like things are shaking out let’s assume that Congress comes to its senses and passes a budget. Suppose the budget is flat, given our inflationary pay increases that have already been approved. In that case, that means we’re going to have to look for offsetting reductions in activities that we do because we have a limited number of people and an overwhelming amount of work,” Califf said.
The implementation and integration of artificial intelligence into clinical practice could have a potential impact on the FDA’s staffing, according to Califf.
“We’d have to hire three or four times as many people to take on what’s coming on, especially given the fact that for predictive AI, that is—you know—giving you information about what’s likely to happen the way algorithms work as you put them in place,” Califf said. “Then they continue to accrue data and experience and they change over time, which means you’re not just approving something like a drug that’s going to be the same drug 10 years later.”
Daiichi Sankyo again raised the revenue forecast for its blockbuster antibody-drug conjugate Enhertu (fam-trastuzumab deruxtecan-nxki), according to its third quarter earnings report for the fiscal year 2023 posted Wednesday.
The Japanese pharma now expects the AstraZeneca-partnered Enhertu to bring in approximately $2.61 billion for the fiscal year 2023, this time driven by growth outside the U.S.
This is the second time Daiichi Sankyo raised Enhertu’s sales forecast this fiscal year. In July 2023, the company set a full-fiscal-year revenue target of approximately $2.18 billion, which it then raised to $2.6 billion during its second quarterly report of the fiscal year posted in October 2023.
According to Daiichi Sankyo’s presentation on Wednesday, Enhertu’s loftier sales outlook is driven primarily by its strong performance in international markets. The pharma similarly raised its revenue outlook in Japan, Europe and the combined Asia and South and Central America market.
However, in the U.S., Daiichi Sankyo lowered its sales expectations for Enhertu to $1.54 billon. The company made the downward adjustment despite 55% year-over-year growth for the therapy’s sales in the country, growing to nearly $1.14 billion in the first nine months of the 2023 fiscal year versus $680 million during the same period the prior year.
Taking its entire business into consideration, Daiichi Sankyo reported a total revenue of around $7.98 billion during the third quarter of fiscal year 2023, representing 23.7% year-over-year growth. According to the company’s presentation, this growth was strongly driven by sales of its anti-influenza drug Inavir (laninamivir) and anticoagulant Lixiana (edoxaban) in Japan.
Daiichi Sanyko’s oncology business was also a major contributor to its growth in the quarter, attributable primarily to Enhertu.
Given its strong performance in the quarter, Daiichi Sankyo also raised its overall revenue outlook to around $10.75 billion for the full 2023 fiscal year, up from $10.54 billion set during the previous quarterly report.
As for pipeline updates, Daiichi Sankyo and partner AstraZeneca are expecting a readout of the Phase III DESTINY-Breast06 study during the first half of the fiscal year 2024. DESTINY-Breast06 is evaluating Enhertu in HR+ and HER2-low breast cancer patients who have not yet undergone chemotherapy.
The partners are also awaiting the FDA’s decision on Enhertu as a treatment option for HER2-expressing solid tumors, with a target action date of May 30.
Despite a sharp COVID-19 sales decline, Roche reported 1% group sales growth for 2023 while predicting mid-single digit sales growth in 2024, according to the company’s financial results announced on Thursday.
The Swiss pharma and diagnostics company is working to overcome weakened demand for its COVID-19 products and currency headwinds by culling its pipeline and looking to acquisitions and collaborations for de-risked assets with “significant potential.”
Excluding COVID-19 medicine Ronapreve, pharma sales increased by 9% from what the company called “ongoing high demand” for its newer medicines like Vabysmo. The eye disease medicine launched in 2022 and has become one of Roche’s best sellers, bringing in $2.78 billion in sales last year.
At the same time, Roche said it has cut several early- to mid-stage candidates from its R&D pipeline—five from neurology and three in oncology/hematology—according to Thursdays full-year 2023 presentation, some of which was previously announced.
Roche’s Genentech ended its longstanding collaboration with AC Immune in January 2024, handing back two Alzheimer’s assets. Study results were not strong enough to merit continuation. In addition, Phase II assets for PTSD and Dup15q syndrome were cut. Both had previously failed in trials for other indications.
In cancer indications, a CD40 agonist for solid tumors was axed along with two bispecific antibodies for glioblastoma and solid tumors.
Despite other cuts earlier in 2023, Roche is still growing its pipeline with 146 new molecular entities and asset expansions. Partnerships and acquisitions have become a focal point to focus on de-risked assets with significant potential, according to the company.
New assets were added to the pipeline from Roche’s attempt to target the lucrative weight loss market. Its merger with Carmot Therapeutics, announced in December 2023, provided Roche with access to three GLP-1 receptor agonists with “best-in-class potential to treat obesity.”
Roche has already made three deals in 2024 totaling a potential $4 billion in payouts, if milestones are met. MediLink Therapeutics scored $50 million for a next-gen ADC for solid tumors. Remix Therapeutics received $30 million for RNA modulating small molecules. Roche also dropped $66 million upfront to MOMA Therapeutics to find new drugs targeting cancer cell growth and survival.
Roche’s oncology trio—Avastin, Herceptin and Rituxan—have faced a growing loss of sales to biosimilar competition, forcing the company to look to newer drugs to counter the losses. In the earnings presentation, CEO Thomas Schinecker reiterated that Roche is looking to acquire drug assets in all states of development.
Sanofi on Thursday released its fourth-quarter and full-year 2023 results revealing an International Financial Reporting Standards net income loss of approximately $600 million, driven mainly by a weak U.S. dollar, high expenses and rising generic competition.
The French pharma’s business operating and net incomes took a hit, dropping 5.2% and 2.7% in the fourth quarter versus the same period the prior year. Operating expenses, meanwhile, grew 7.1% to around $5.19 billion.
Contributing strongly to the decline was Sanofi’s multiple sclerosis therapy Aubagio (teriflunomide), the sales of which dropped 74% to just over $130 million in the fourth quarter after its loss of exclusivity, according to the company’s presentation.
Still, the pharma posted positive growth for its net sales in the fourth quarter, raking in more than $11.8 billion, which represents 9.3% growth at constant exchange rates compared with the same period the prior year. Its full-year 2023 sales, which came in at around $46.6 billion, posted 5.3% growth from the previous year.
The blockbuster anti-inflammatory drug Dupixent (dupilumab) was once again Sanofi’s top-selling asset, netting approximately $3.23 billion in the fourth quarterwith 31.3% revenue growth. Despite sustaining a 4% drop in sales, Sanofi’s portfolio of influenza vaccines brought in a combined $741 million and remains one of the company’s best-performing product categories.
Other high-performance assets in the fourth quarter of 2023 included Sanofi’s polio, pertussis and Hib vaccines, as well as its preventive antibody for respiratory syncytial virus Beyfortus (nirsevimab).
Looking forward to 2024, Sanofi and partner Regeneron are looking to boost Dupixent’s earnings further with a potential approval in chronic obstructive pulmonary disease (COPD). The companies posted data from the Phase III BOREAS trial in March 2023 and the Phase III NOTUS study in November 2023, showing that Dupixent could significantly reduce episodes of exacerbations in COPD patients.
Dupixent is also in Phase III studies for bullous pemphigoid, chronic pruritus of unknown origin, chronic spontaneous urticaria and eosinophilic gastritis, submissions for which are planned for 2025 and beyond.
Sanofi is also preparing to make a handful of regulatory submissions this year, including for tolebrutinib in relapsing multiple sclerosis and non-relapsing secondary progressive multiple sclerosis, fitusiran in hemophilia A and B and rilzabrutinib in immune thrombocytopenia.
On Thursday, Sanofi named François-Xavier Roger as its new chief financial officer, replacing Jean-Baptiste Chasseloup de Chatillon who will move on to lead a charity for children. Roger was most recently the financial head of Nestle, where he served for over eight years and drove the company’s “sustainable value creation,” according to the announcement.
Roger was also previously the CFO of Takeda and Danone Asia, and had worked for other pharma companies including Aventis, Roussel and Hoechst.
https://www.biospace.com/article/sanofi-hit-with-600m-net-loss-in-q4-amid-generic-competition-/
With the opioid epidemic continuing to ravage the U.S., Vertex's announcement Tuesday that its non-opioid pain treatment VX-548 led to “significant improvement” in pain in two Phase III trials was widely hailed as a breakthrough. But the investigational drug did miss the first key secondary endpoint: superiority to a combination of the opioid hydrocodone bitartrate and Tylenol—a duo branded as Vicodin. This raises the question: Is it possible to do better?
Both trials—one testing VX-548 following abdominoplasty (tummy tuck) surgery, the other following bunionectomy surgery—hit the primary endpoint of statistically significant reduction of pain intensity from 0 to 48 hours. VX-548 failed, however, to beat Vicodin on the same scale.
During an investor call Tuesday, analysts also questioned the drug’s performance on another key secondary endpoint: median time to pain relief. In both indications, VX-548 had a “more rapid onset to meaningful pain relief” than placebo, Vertex reported, with median time to pain relief being two hours in tummy tuck patients and four hours in bunionectomy patients versus eight hours for the placebo group. Analysts on the call also appeared to be seeking faster time to pain relief, with Leerink Partners’ David Risinger asking if Vertex’s Phase I NaV1.8 inhibitors may offer a quicker onset.
Vertex CEO Reshma Kewalramani responded, saying, “If it is possible to get even better than VX-548, we are determined to be the ones who do so.”
Stuart Arbuckle, the company’s chief operating officer, also responded to questions from analysts, including how payors would respond to the drug’s efficacy. The “significant adverse events” and addictive potential associated with opioids are a major deterrent, he noted, adding that he believes payors will “warmly welcome the advent of a truly non-opioid pain med as this compelling combination of efficacy and safety and tolerability.”
When pressed for further details on the missed endpoint, Vertex representatives directed BioSpace to the investor call.
VX-548 is a novel NaV1.8 pain signal inhibitor with a rich history. “The mechanistic evidence for [NaV1.8], even in the year 2001, was crystal clear,” said Stephen Waxman, a professor of neurology at Yale School of Medicine. “If you could shut it off, you had a good chance of attenuating pain.” This is around the time Vertex began its efforts against NaV1.8, which would ultimately yield VX-548, Waxman said.
Waxman, whose work contributed to the revelation that the NaV1.7, NaV1.8 and NaV1.9 sodium channels played a central role in pain signaling, highlighted three possible reasons for VX-548’s failure to beat Vicodin.
“One possibility is that [Vertex] did a good job on dosing but didn’t get it precisely right,” he said. “There could have been a higher dose with higher efficacy.” A second possibility, he said, is that a second-generation drug “will have more potency, more effective distribution, fewer side effects, be able to be dosed better and give better efficacy.”
Lastly, Waxman suggested that NaV1.8 may be “important enough in pain signaling that you get this degree of reduction of pain when it is blocked, but there is some redundancy in the pain pathway, so block of NaV1.8 reduces pain but does not totally abolish it.”
He likened VX-548 to the early days of the statin drugs. “The very first statin drugs worked, but in retrospect, they were not optimal, and the real bang for the buck in terms of societal impact was in the second and third-generation drugs,” he said. “And that’s where I think we are right now.”
As for what a second-generation drug might look like, Waxman noted that there are many approaches to targeting NaV1.8, including small-molecule blockers, peptide blockers, toxin derivatives, antibodies, knockdown therapies and gene therapy approaches.
“Now that we know that [NaV1.8] is a druggable target and we know that blocking it reduces pain, we have proof of concept in humans,” Waxman said. “That raises the exciting question of whether there are there other ways to attack 1.8, and there undoubtedly are. It is a very exciting time in the search for new, non-addictive pain medications.”
A federal court in Delaware heard arguments Wednesday in a key lawsuit challenging Medicare drug-negotiation provisions of the Inflation Reduction Act (IRA). Reports from inside the courtroom suggested that the judge was skeptical of the arguments raised by plaintiff AstraZeneca, though experts told BioSpace this is just an early step in what could be a protracted series of legal battles.
Thursday, the Centers for Medicare and Medicaid Services (CMS) is due to release its proposed maximum fair price for the initial set of 10 single-source drugs chosen for negotiation, after which time, drug companies will have 30 days to respond.
While no ruling on AstraZeneca’s motion for summary judgment is expected for about a month, court activity will heat up over the next few weeks, as a total of 10 cases from pharma companies and groups have challenged various aspects of the IRA’s Medicare drug-pricing provisions. Other plaintiffs include Merck, Novartis, Johnson & Johnson, Bristol Myers Squibb, Boehringer Ingelheim, Novo Nordisk and the lobbying group Pharmaceutical Research and Manufacturers of America (PhRMA).
Most are currently seeking summary judgment. There has been no ruling to date that would change or delay the regulatory path CMS and the Department of Health and Human Services (HHS) are pursuing. As of now, CMS is on schedule to publish negotiated rates by Sept. 1 that will take effect in January 2026, but the legal process is a long one.
“All of these cases ultimately have the potential to be appealed, and no doubt will be appealed,” said John Bennett, a Boston-based litigator at Allen & Overy who works with biopharma clients. “I think all of them in one shape or form have the possibility at least of potentially becoming precedent and potentially being argued at the Supreme Court.”
The earliest suit, filed by Merck last June, claimed that the IRA violates that company’s First Amendment rights by forcing the firm to endorse speech it disagrees with and its Fifth Amendment rights by taking assets without compensation. AstraZeneca is also claiming a Fifth Amendment violation, but Judge Colm Connelly reportedly questioned whether the law amounts to an unconstitutional seizure.
Other litigants have cited due process arguments under the Fifth and Fourteenth Amendments, according to an analysis published in Health Affairs. PhRMA contended that the civil fines included in the IRA goes against the Eighth Amendment, which prohibits excessive fines.
AstraZeneca is taking a different tack altogether, choosing to focus on the logistics of the IRA’s implementation rather than the law’s constitutionality in pursuit of changes to the implementation plan. “[It’s] somewhat unique in that it is challenging some of the regulatory guidances that CMS has issued in the wake of the legislation passing,” Bennett said.
He added that it’s still unclear whether the AstraZeneca approach or the strategy favored by other drug companies will be more effective in court. “I think some of the constitutional arguments that have been raised are legitimate arguments,” Bennett said. “Whether or not they would ultimately succeed I think largely will depend on whether or not the industry can get some more traction on its argument that compliance with this regime and program really is not voluntary.”
Debbie Hart, president and CEO of BioNJ, a life sciences trade association in New Jersey, said in an email that she agrees with the claim that the IRA is essentially forcing drugmakers to bend to the will of the government rather than engage in true negotiation. “As a result, life sciences companies are in a position to ultimately accept a stipulated price or withdraw from the Medicare and Medicaid programs entirely, effectively barring all of the patients under those programs from access to those medications,” Hart told BioSpace.
The AstraZeneca suit in particular, with its focus on execution, demonstrates how CMS went “well beyond the letter of the law,” she added.
AstraZeneca did not respond to BioSpace's request for comment.
Immediate attempts to stall the IRA’s implementation have failed. In late September, a federal judge threw out a motion for preliminary injunction by the Dayton (Ohio) Area Chamber of Commerce to block implementation of Medicare drug price negotiation. And the court in Delaware will not rule on Wednesday's AstraZeneca hearing until March 1, so CMS has no reason to pause its work, according to Kelly Bagby, vice president of litigation at AARP Foundation, which has filed several amicus briefs supporting Medicare drug price negotiation.
Whether courts set any precedent for Medicare drug price negotiation may depend on how cases are consolidated and how quickly the inevitable appeals process moves, according to the experts who spoke with BioSpace.
Bagby predicted that any appeals in the AstraZeneca suit in Delaware would be combined into the U.S. Court of Appeals for the Third Circuit, which also covers New Jersey, since the pending J&J, BMS, Novo Nordisk and Novartis cases were all filed there. “It seems likely that these five cases could be heard on appeal together,” Bagby told BioSpace in an email.
Bennett said it is hard to forecast whether any of the ongoing cases might prevail in blocking or altering IRA implementation, but he said to keep an eye on an upcoming Supreme Court ruling on a 40-year-old precedent called “Chevron deference,” which the high court reviewed last month. That doctrine holds that an administrative agency’s interpretation of a statute is “entitled to some measure of deference when the issue is litigated before a federal court,” Bennett explained.
A commentary in SCOTUSblog suggested that the Supreme Court was likely to overturn the 1984 ruling. Such a reversal could bolster the drug companies’ arguments, according to Bennett, or at least make it more likely that the high court would eventually take up the inevitable appeals regarding Medicare drug price negotiation.
“There will be decisions that will be coming down this calendar year that will be important,” Bennett said, “and it is something that obviously bears watching for the foreseeable future with multiple different courts and multiple different judges weighing in.”
