Merck's Blockbuster Cancer Drug Keytruda Secures FDA Approval For Biliary Tract Cancer

 The FDA approved Merck & Co Inc's MRK Keytruda, in combination with gemcitabine and cisplatin, for locally advanced unresectable or metastatic biliary tract cancer (BTC). 

The approval was based on results from the Phase 3 KEYNOTE-966 trial, in which Keytruda plus chemotherapy demonstrated a statistically significant improvement in the study's primary endpoint of overall survival (OS), reducing the risk of death by 17% compared to chemotherapy alone at the trial's pre-specified final analysis for OS. 

Median OS was 12.7 months for Keytruda plus chemotherapy versus 10.9 months for chemotherapy alone. 

This approval marks the sixth indication for Keytruda in gastrointestinal cancers.

Merck also released data from the Phase 3 KEYNOTE-564 trial evaluating Keytruda versus placebo as adjuvant therapy for certain patients with renal cell carcinoma (RCC) following nephrectomy (surgical removal of a kidney).

The study met its key secondary endpoint of overall survival (OS).

At a pre-specified interim analysis review conducted by an independent Data Monitoring Committee, Keytruda demonstrated a statistically significant and clinically meaningful improvement in OS compared to placebo. 

As previously reported, at an earlier pre-specified interim analysis with a median follow-up of 23.9 months, KEYNOTE-564 met its primary endpoint of disease-free survival (DFS), reducing the risk of disease recurrence or death by 32% compared to placebo. 

https://www.benzinga.com/general/biotech/23/11/35542883/mercks-blockbuster-cancer-drug-keytruda-secures-fda-approval-for-biliary-tract-cancer

Eyenovia started at Buy by Blair

 William Blair initiated coverage on Eyenovia Inc EYEN, a biopharma company focused on developing therapies based on its Optejet device, which leverages a microdose array print (MAP) technology that allows consistent, reproducible dosing of ophthalmic drugs. 

Analysts Tim Lugo, Lachlan Hanbury-Brown, and John Boyle have initiated an Outperform rating, with an estimated fair value for shares of $3.

The fair value is based on a risk-adjusted net present value (NPV) for MydCombi, APP13007, and the company's clinical-stage pipeline of two additional assets using the Optejet technology as well as royalties and milestones from U.S. and ex-U.S. partnerships.

The company recently received approval for MydCombi, which will be marketed to the eye care market for the common eye procedure of pupil dilation (mydriasis). 

The analysts anticipate this market initially to be limited for Eyenovia. However, the approval validates the Optejet drug device.

In addition to MydCombi, Eyenovia is actively advancing treatments for progressive myopia in children presbyopia and has recently acquired the U.S. rights to APP13007, a potent topical steroid intended for post-ocular surgery use, currently undergoing FDA review with a PDUFA date set for March 4, 2024.

William Blair notes Eyenovia's product pipeline portfolio and says it presents a noteworthy opportunity for strategic partnerships with major players in the eye care industry. 

These collaborations can help develop solutions for glaucoma, dry eye disease, and post-operative therapies following cataract surgery. 

In the U.S., these expansive markets collectively cater to approximately 40 million patients, making them a significant focus for Eyenovia's growth and impact.

In the coming year, William Blair anticipates Eyenovia's expansion of manufacturing operations in Redwood City, which is expected to pave the way for achieving profitability with the Optejet platform and the advancement of next-generation device development.

https://www.benzinga.com/general/biotech/23/11/35543533/eyenovias-stock-is-soaring-today-heres-why

US Mulling 'Day After' Hamas, Including An International Peacekeeping Force In Gaza

 Washington is already mulling the "day after" as Israel has vowed to eradicated Hamas from the Gaza Strip. Already over a million Gazans have been displaced within the Strip, according to UN figures, as Israeli tanks push deeper into Gaza City in the north.

Both Bloomberg and Politico have this week reported that US officials are in discussions to possibly establish a multinational peacekeeping force that would be sent to the Gaza Strip, given that a massive humanitarian catastrophe is fast unfolding. The plan is being mulled in preparation for after Hamas is finished, and based on fears of post-war total societal breakdown which could in turn breed further home-grown terrorist violence. 

Democratic Sens. Richard Blumenthal of Connecticut and Chris Van Hollen and Ben Cardin of Maryland disclosed the "very preliminary and fragile" closed-door discussions to the publications. 

Van Hollen has been cited as saying he believes it's "important to have some kind of multinational force in Gaza as a transition to whatever comes next." However, the White House has at the same time cautioned that putting US troops on the ground in Gaza is "not something that’s being considered or is under discussion" - according to NSC spokesperson Adrienne Watson.

The Pentagon has admitted though that special forces are in Israel advising Israeli defense and intelligence officials, as the two countries consult on how to best locate and rescue the some 240 hostages held by Hamas.

Sen. Blumenthal has been quoted as saying, "There certainly has been discussion with the Saudi[s] about their being part of some international peacekeeping force if only to provide resources, and ... supporting Palestinian leadership and a separate stat."

"Reconstruction of Gaza will require a vast amount of resources, which the Saudis potentially could help provide," Blumenthal said further, and added that "an international force could be mustered without U.S. troops."

Washington has lately backed off rhetoric that might be seen as supporting a controversial Israeli 'option' to send Gazans into tent cities in the Sinai - widely denounced by international organization as tantamount to ethnically cleansing the historic and densely populated Strip. 

There are reports that Israel has offered Egypt major incentives for this to happen: 

Israel is proposing writing off a significant chunk of Egypt’s international debts through the World Bank to entice the cash-strapped Abdel Fattah el-Sisi government to open its doors for displaced Palestinians, according to the Israeli Ynet website.

Egypt is currently mired in a debt crisis, ranking second only to Ukraine among countries most likely to default in debt payments.

The state is haemorrhaging half its revenue in interest payments and is reliant on loans from the IMF and wealthy Gulf states, limiting its ability to contradict US foreign policy.

But it's entirely another open question whether Israel would actually have this much sway with the World Bank to write off Egypt's extensive international debts. 

Israel and the US are mulling various 'options' for handing the civilian side of the crisis in large part due to the intensifying international pressure over the immensely high death toll, which has surpassed 9,000 mostly civilians. Countries especially across the Global South have been denouncing the humanitarian catastrophe, with some actually breaking off diplomatic ties and removing ambassadors - Bahrain is the latest to do so.

https://www.zerohedge.com/geopolitical/us-mulling-day-after-hamas-including-international-peacekeeping-force-gaza

Merus results, update

 Petosemtamab in combination with Keytruda 1L initial interim clinical data planned for 1H24; 2L+ HNSCC monotherapy clinical update planned 2024

– Zeno interim clinical data continue to show robust efficacy in NRG1+ NSCLC and PDAC: Sufficient clinical data expected in 1H24 to support potential BLA submissions

– Based on the Company’s current operating plan and recent oversubscribed public offering raising approximately $172M gross proceeds, existing cash, cash equivalents and marketable securities expected to fund Merus’ operations into 2027

https://www.globenewswire.com/news-release/2023/11/02/2772843/37568/en/Merus-Announces-Financial-Results-for-the-Third-Quarter-2023-and-Provides-Business-Update.html

1 paycheck not enough: Digital bank Current finds almost half its customers have multiple jobs

 The need for second — and often third — incomes is mounting, according to a top digital bank executive.

Current CEO Stuart Sopp finds almost half of the firm’s payment customers have more than one job.

“If you’re having a paycheck over the past year, 20, 25% of paycheck depositors have at least one extra job. A further 20% incremental from there have two jobs,” Sopp told CNBC’s “Fast Money” on Thursday. “They’re trying to make that money go further because of inflation.”

From DoorDash to Shopify to side businesses, Sopp finds the number is higher than prior years because money doesn’t go as far.

“Wage inflation is moderating quite substantially,” he said. “America has a sort of tail of two cities right now. Two groups: The wealthy and less affluent.”

Sopp launched Current, which provides mobile banking without monthly fees and offers secured credit cards, in 2015. It originally focused on helping medium to lower income customers. His company Current reports almost five million members.

He’s particularly concerned about less affluent consumers spiraling into debt to pay for basic necessities.

“They’re being forced into risks like risky credit cards,” noted Sopp, a former Morgan Stanley trader. “Unsecured credit cards... are not suitable for everyone.”

The Federal Reserve Bank of New York found credit card debt topped $1 trillion for the first time ever in the second quarter.

“It’s going to be way bigger this year,” Sopp said.

https://www.cnbc.com/2023/11/02/one-paycheck-too-small-half-of-currents-customers-have-multiple-jobs.html

People Who Need 988 Find It, but Many Say They Won't Use It Again

 People in serious distress were more likely to have heard of and use the 988 Suicide and Crisis Lifeline, but many said they probably wouldn't use it again.

In a survey of nearly 5,000 U.S. adults, those with serious distress were significantly more likely to have heard of the lifeline, which launched in July 2022, than those with no distress (47.4% vs 40.4%, P=0.007), according to Jonathan Purtle, DrPH, MSc, of New York University in New York City, and colleagues.

And a larger proportion of those with serious distress used the lifeline compared with those with moderate or no distress (6% vs 1% and 0.2%, P<0.001), they reported in JAMA Network Openopens in a new tab or window.

But a smaller proportion of those with serious distress reported being very likely to use 988 in the future compared with those with no distress (22.3% versus 26.2%), though this wasn't statistically significant, they found.

"Our data suggest the 988 Lifeline is being used the most by people with serious psychological distress, which is a good thing," Purtle told MedPage Today in an email.

But he acknowledged that a "smaller proportion of people than we expected reported being 'very likely' to use the 988 Lifeline in the future if they or a loved one were experiencing suicidality or a mental health crisis. However, data not presented in the current study show that similarly small proportions of people were very likely to reach out to sources such as a mental health professional, psychologist [or] psychiatrist, friend [or] family member, or someone in their religious network."

Christine Crawford, MD, MPH, a psychiatrist at Boston University who wasn't involved in the study, told MedPage Today that the lower likelihood of using 988 or planning to use it again could be attributed to an individual's expectations.

"The supports that are available through 988 look different depending on which part of the country you live in because it's all based on available community resources," Crawford said, noting that wait times or delays can be particularly discouraging.

Those delays may leave some respondents reconsidering calling 988 again, she added. Crawford noted that expectations can also differ based on an individual's race.

"On average, people who experience higher rates of psychological distress tend to be Black and brown individuals," she said. "What we do know to be true is that historically, Black and brown individuals are quite reluctant to call 911. I wonder if that factors into 988, given that there are situations in which when you do call 988, the police will still arrive at your house."

For their study, the researchers conducted a nationally representative web-based survey from June 9 to June 19, 2023. Past 30-day psychological distress was assessed using the Kessler K6 Scale. Respondents were asked whether they had heard of 988, had used 988 for themselves, and whether they would be likely to use it in the future.

A total of 4,942 respondents completed the psychological distress questionnaire. About half were female (51%) and the mean age was 48.1 years. Nearly 8% had serious distress, 20.4% had moderate distress, and 71.8% had no distress.

In adjusted analyses, having serious or moderate distress was significantly associated with higher odds of having heard of the 988 Lifeline compared with those with no distress (adjusted OR 1.45, 95% CI 1.16-1.82, P=0.001 and aOR 1.27, 95% CI 1.09-1.47, P=0.002, respectively).

Serious distress was also significantly associated with a far higher likelihood of having called 988 compared with those with no distress (aOR 31.96, 95% CI 12.01-85.08, P<0.001). Moderate distress was also tied to a greater odds of having called 988 but to a lesser extent (aOR 5.15, 95% CI 1.78-14.89, P=0.003), the researchers reported.

As for calling the hotline again, the researchers found that among the 23 respondents with serious distress who'd called once, only 7 (29%) were very likely to use it in the future.

The study may be limited in its generalizability, and by the fact that implementation of the 988 hotline has varied between states. State-level analyses weren't conducted.

Still, Purtle and colleagues concluded that there is "a need for more research about satisfaction with the 988 Lifeline among people with serious distress and the extent to which the 988 Lifeline, and the resources it connects users to, meets their needs."

Disclosures

The authors disclosed no financial conflicts of interest.

Primary Source

JAMA Network Open

Source Reference: opens in a new tab or windowPurtle J, et al "Use, potential use, and awareness of the 988 suicide and crisis lifeline by level of psychological distress" JAMA Netw Open 2023; 6(10): DOI: 10.1001/jamanetworkopen.2023.41383.

https://www.medpagetoday.com/psychiatry/generalpsychiatry/107111

JAK Inhibitor Safety Study Seen Altering Practice in the VA

 Safety risks found in a postmarketing trial with the Janus-associated kinase (JAK) inhibitor tofacitinib (Xeljanz) appear to have influenced prescribing patterns across the class for rheumatoid arthritis (RA) patients in the Veterans Affairs (VA) health system, researchers found.

Following publication of the ORAL Surveillance dataopens in a new tab or window in January 2021, older RA patients in the VA system and those with substantial cardiovascular risk factors were more likely to discontinue JAK inhibitors, compared with the previous 22 months, according to Joshua F. Baker, MD, MSCE, of the University of Pennsylvania in Philadelphia, and colleagues.

Such patients also got fewer new tofacitinib prescriptions, the group reported in Arthritis Care & Researchopens in a new tab or window.

ORAL Surveillanceopens in a new tab or window was conducted by tofacitinib's manufacturer, Pfizer, under orders from the FDA after some data from its registration trials and postmarketing reports had suggested that the drug increased risks for certain cancers and major cardiovascular events. The active-comparator trial enrolled more than 4,600 RA patients, assigning them 1:1 to tofacitinib or a tumor necrosis factor (TNF) inhibitor.

Major findings were that patients given tofacitinib incurred about 50% more new malignancies than did the TNF inhibitor group; cardiovascular events were also about one-third more common with the JAK inhibitor. Moreover, the study showed that the risk increase was especially prominent in older patients and those with preexisting conditions. These results prompted the FDA to require sterner boxed warnings about cardiovascular and cancer risk for all JAK inhibitors.

In September, Baker's group published an analysis of VA dataopens in a new tab or window showing that overall JAK inhibitor use had dropped in the wake of the ORAL Surveillance data. But the researchers also wanted to know whether this shift in prescribing affected all patient subgroups or only those seen most at risk. That was the focus of their new study.

Baker and colleagues examined tofacitinib prescriptions for RA in the VA system from April 2019 to September 2022, i.e., 664 days prior to and after the January 2021 announcement of ORAL Surveillance data.

A total of 2,111 patients started on new courses of tofacitinib in the earlier period versus 1,664 after the announcement. Mean age of these new initiators also declined, from 64.1 to 63.0.

"There were also decreases in the proportion with cardiovascular comorbidities including hypertension, hyperlipidemia, heart failure, coronary artery disease, vascular disease and cerebrovascular disease, skin cancer, and lymphoproliferative disorders (all P<0.05)," the researchers wrote. These declines were mostly in the range of 4-5 percentage points, except for coronary artery disease, for which the decrease was about 8 points (from prevalence of 33% to 25%).

Some of these patterns were reversed for TNF inhibitor prescriptions. Mean age of new users of these drugs increased, as did the prevalence of diabetes, prostate cancer, and lymphoproliferative disorders.

Discontinuation rates also were higher, by 18% (P<0.001), for tofacitinib versus TNF inhibitors after the ORAL Surveillance data came out. This difference was doubled to tripled for patients with various cardiovascular conditions.

Limitations of the study included its conduct among VA patients, whose demographics differ markedly from the general population and who face fewer issues with insurance coverage. Also, it's possible that the VA's electronic records system may have played a role in physicians' decisions. And the study period spanned the appearance of COVID-19, which might have altered practice patterns as the pandemic evolved.

Disclosures

Funding for the study came from the VA health system. One co-author served on the steering committee for ORAL Surveillance and consulted for other pharmaceutical companies. Two other authors, including Baker, reported relationships with companies including Boehringer Ingelheim, CorEvitas, Cumberland Pharma, and Burns-White.

Primary Source

Arthritis Care & Research

Source Reference: opens in a new tab or windowSong S, et al "Changes in characteristics of patients initiating and discontinuing advanced therapies for rheumatoid arthritis following the release of safety data" Arthritis Care Res 2023; DOI: 10.1002/acr.25268.

https://www.medpagetoday.com/rheumatology/arthritis/107131