FDA Creates Adcomm for Genetic Metabolic Diseases and Potential Treatments

 The FDA on Tuesday announced it is establishing a new advisory committee that will discuss and evaluate potential treatments for genetic metabolic diseases which disrupt the body’s metabolism.

According to the regulator’s announcement, the new panel will be called the Genetic Metabolic Diseases Advisory Committee and will provide “independent, knowledgeable advice” when called upon, as well as “recommendations on technical, scientific and policy issues” around proposed products targeting indications in this therapeutic space.

The advisory committee’s purview will cover products for the diagnosis, prevention or treatment of genetic metabolic diseases under the Division of Rare Diseases and Medical Genetics.

Janet Maynard, director of the Office of Rare Diseases, Pediatrics, Urologic and Reproductive Medicine under the FDA's Center for Drug Evaluation and Research, said in a statement that drug development for genetic metabolic diseases “has unique and complex challenges.”

“This new advisory committee will provide a forum for discussion of complicated issues with specialized and diverse technical and scientific experts in the field of metabolic genetics,” Maynard said.

The Genetic Metabolic Diseases Advisory Committee will have nine voting members, including a chairperson and various experts in the areas of metabolic genetics, small population trial design, management of inborn errors of metabolism, epidemiology or statistics, pediatrics, translational science and other related fields.

Representatives for consumers and for the industry will also sit on the advisory committee.

The FDA is currently seeking members for the Genetic Metabolic Diseases Advisory Committee and has put out a call for nominations.

This new adcomm comes as the biopharma industry’s interest in genetic therapies reaches an all-time high—and as the agency anticipates an uptick in regulatory applications.

Last week, the FDA handed out back-to-back approvals for this therapeutic modality, one for Vertex Pharmaceuticals and CRISPR Therapeutics’ Casgevy (exagamglogene autotemcel) and another for bluebird bio’s Lyfgenia (lovotibeglogene autotemcel), both for sickle cell disease.

Ahead of a potential upswell in FDA filings, the FDA’s Center for Biologics Evaluation and Research is reevaluating its regulatory guidelines, including looking at the level of uncertainty acceptable at the time of approval as well as the types of efficacy evidence that it can consider for approval.

In April 2023, Applied Therapeutics announced that it would still file a New Drug Application for its drug candidate govorestat in galactosemia, a rare genetic metabolic disease. Govorestat was unable to improve a composite endpoint of clinical symptoms but did induce “systematic improvement over time,” which according to Applied Therapeutics should be enough for a submission.

https://www.biospace.com/article/fda-creates-adcomm-for-genetic-metabolic-diseases-focusing-on-potential-treatments/

Pfizer’s 2024 Outlook Disappoints Wall Street, Plans $500M in Additional Cost Cuts

 Pfizer has been under financial pressure and is still on a downward trajectory as the end of the year approaches. The company’s full-year 2024 guidance suggests that revenue next year could fall or come in flat compared to 2023, while it plans an “incremental” $500 million cost reduction, according to an announcement on Wednesday.

Pfizer’s stock dropped around 7% on Wednesday morning before the opening bell and has fallen over 46% since the beginning of the year.

In the company’s year-end guidance on Wednesday, Pfizer said it expects to bring in revenues of around $58.5 billion to $61.5 billion in 2024. According to CNBC, analysts anticipated an average guidance of nearly $63.2 billion in revenues.

Sales of the COVID-19 products Comirnaty and Paxlovid are expected to bring around $8 billion in revenues into Pfizer’s coffers for the year. While Pfizer also projects around $3.1 billion in revenue from its Seagen acquisition.

Pfizer's $43 billion deal to acquire antibody-drug conjugate maker Seagen cleared all regulatory issues on Tuesday and is expected to close on Thursday.

Excluding the COVID-19 products and Seagen revenues, Pfizer expects full-year 2024 operational revenue growth of 3% to 5%.

“Pfizer’s product portfolio remains strong. In 2024, Comirnaty and Paxlovid are expected to deliver combined revenues of approximately $8 billion, and our remaining portfolio of combined Pfizer and Seagen products is expected to achieve year-over-year operational revenue growth in the range of 8% to 10%,” Pfizer CEO Albert Bourla said in a statement. 

However, financial pressures have been building for the New York-based company throughout the year. In the third quarter of 2023, Pfizer encountered its first quarterly loss since 2019, with significant drops in the sales of the Comirnaty vaccine and Paxlovid.

The biopharma giant started a major cost-cutting initiative in October 2023, seeking to save around $3.5 billion through 2024, which has now been raised to $4 billion in total so far.

“We expect our cost realignment program to deliver savings of at least $4 billion by the end of 2024, which puts us on a path to potentially regain our pre-pandemic operating margins,” Bourla said in a statement. 

Cost-cutting initiatives have included closing several manufacturing facilities and layoffs on the production side of the business in both the U.S. and Europe. Last month, Pfizer announced 500 staff layoffs were coming at a U.K. facility, while another 100 jobs were axed at a production site in Ireland.

https://www.biospace.com/article/pfizer-s-2024-outlook-disappoints-wall-street-plans-additional-500m-in-cost-cuts-/

Boots IPO Would Give a Needed Boost to London’s Ailing Bourse

 

• UK pharmacy could be valued at £7 billion, Bloomberg reports
• London listing volume slumps to lowest in more than a decade

The potential return of UK drugstore chain Boots to the London stock exchange could be the market’s biggest initial public offering in years.

Walgreens Boots Alliance Inc., has been holding early talks about ways to separate Boots, which could be valued at about £7 billion ($8.8 billion), Bloomberg News reported. It’s studying a London initial public offering as one possibility, people with knowledge of the matter said.

https://www.bloomberg.com/news/articles/2023-12-13/a-boots-ipo-would-give-a-needed-boost-to-london-s-ailing-bourse

Verastem starts Phase 3 ovarian cancer trial

 RAMP 301 Is Evaluating the Combination of Avutometinib and Defactinib vs Investigator’s Choice of Therapy

Reported Data from Part A of RAMP 201 Trial Show an Objective Response Rate of 45%, and Manageable Safety and Tolerability Profile with the Combination

Company Intends to Submit an Accelerated Approval New Drug Application to the U.S. Food and Drug Administration for the Combination Based on Breakthrough Therapy Designation and Mature Data from RAMP 201 and FRAME Trials

https://www.businesswire.com/news/home/20231213489476/en/

Hamas Leaders Flee Qatar, Enter Hiding, After Israel Declares They'll Be Hunted Down

 Following the end of the weeklong Israel-Hamas truce, there were international efforts to revive the Doha-based negotiations, but to no avail. Since then, Israel's military has only expanded ground operations to the south of the Gaza Strip, where tanks have been seen in the center of Khan Younis amid fierce fighting.

After earlier this month Prime Minister Netanyahu ordered Mossad negotiators home from Qatar, there were still hopes that behind-the-scenes efforts at mediating another temporary truce could be salvaged. But these have been dashed on reports that key Hamas officials involved in the talks have also exited Qatar this week.

"Several Hamas leaders left Qatar for an unknown destination, turning off their phones and not accepting calls, KAN's Arabic language channel reported citing sources in Doha on Tuesday evening," The Jerusalem Post writes.

"Additionally, on Tuesday, KAN news reported that Saleh al-Arouri, a senior member of Hamas, left his usual residence in Beirut for Turkey," the report continues.

Palestinian and other regional sources have also suggested that Hamas officials are fleeing their hideouts abroad, after Israel's government made clear it would target and hunt down Hamas operatives abroad.

According to The Messenger, "Top Hamas leaders have reportedly left their luxury safe haven in Doha, the Qatari capital, according to a report from Israel’s KAN state radio’s Arabic Service, and may be headed to Algiers or Tehran to evade capture or assassination at the hands of Israel."

One Palestinian news source said that top Hamas officials, who have for years lived in luxury in Qatar as a kind of government in exile, could no longer have their safety guaranteed. While it remains unconfirmed, Gaza Report details the following: 

More details on this matter: 3 top officials suddenly vacated their offices in Doha and left the country. They took with them their drivers and advisors, and they completely disconnected their phones. Their destination, whether it be Beirut, Algiers, or Tehran is not confirmed.

These developments suggest that there is no connection now with either the political leadership or the Gaza military leadership and any discussions of a ceasefire that were raised by the Israelis recently are not realistic until contact is reestablished.

If accurate, Hamas' top leadership essentially going "underground" would mean any realistic attempts at peace negotiations would be all but impossible. Qatar and other third party countries have reportedly been pressing for new ceasefire dialogue. Israeli leaders have appeared to shut the door on the possibility for the time being, after Netanyahu pledged to see through his stated goal of completely eradicating Hamas.

Hamas leadership, including top chief Ismail Haniyeh, has long been criticized for staying in luxury hotels abroad while Gazans suffer the effects of their decision-making...

Just last week, Israel signaled it is prepared to take the war on Hamas far beyond the confines of Gaza and the West Bank. The country's security chief referenced "our Munich" in relation to planned efforts to hunt down notable Hamas operatives residing in foreign states.

"The cabinet has set us a goal, in street talk, to eliminate Hamas. This is our Munich. We will do this everywhere, in Gaza, in the West Bank, in Lebanon, in Turkey, in Qatar," said Ronen Bar, who is the head of Israel's domestic security agency Shin Bet. He emphasized, "It will take a few years but we will be there to do it." Israel has long been known to conduct aggressive and high risk assassination campaigns abroad, especially in Iran of late.

"Our Munich" is in reference to Israeli intelligence's most famous targeted assassination covert operation in history, in response to the 1972 killings of 11 Israeli Olympic team members. Terrorists belonging to the Palestinian Black September had launched an unprecedented attack on the Munich games. Some eight members of the radical group had breached the Olympic compound and entered the two apartments used by the Israeli team, after which they began executing athletes amid a hostage standoff.

From there began a process on the part of Israeli intelligence to hunt down the Munich killers over a period of several years and spanning different countries. Israeli intelligence had dubbed the covert operation - details of which only became known decades later - as the "Wrath of God".

Meanwhile, the below is what Israel and its Western allies are worried about in terms of the potential for Hamas or Hamas-inspired terror attacks abroad...

https://www.zerohedge.com/geopolitical/hamas-leaders-flee-qatar-enter-hiding-after-israel-declares-theyll-be-hunted-down

ReShape Gets Supplement Approval for its Next-Generation Lap-Band

 ReShape Lifesciences® (Nasdaq: RSLS), the premier physician-led weight loss and metabolic health solutions company, today announced that the U.S. Food and Drug Administration (FDA) has granted approval of a PMA supplement for the company’s next generation, enhanced Lap-Band® 2.0 FLEX.

https://www.globenewswire.com/news-release/2023/12/12/2795114/0/en/ReShape-Lifesciences-Receives-FDA-PMA-Supplement-Approval-for-its-Next-Generation-Lap-Band-2-0-FLEX.html

C4 upped to Buy from Hold by Stifel

 Target to $12 from $2

https://finviz.com/quote.ashx?t=CCCC&p=d