ImmunoGen: Additional Analyses of Mirvetuximab Soravtansine in Ovarian Cancer at ESMO

 Patient-Reported Outcomes with Mirvetuximab Versus Chemotherapy in FORWARD I Study Reinforces Differentiated Tolerability Profile

ImmunoGen, Inc. (Nasdaq: IMGN), a leader in the expanding field of antibody-drug conjugates (ADCs) for the treatment of cancer, today announced findings from an analysis of patient-reported outcomes (PROs) with mirvetuximab soravtansine (mirvetuximab) versus chemotherapy in the randomized Phase 3 FORWARD I study in platinum-resistant ovarian cancer. The Company also announced population pharmacokinetic (PK) and exposure response (ER) analyses across multiple clinical trials evaluating mirvetuximab monotherapy in folate receptor alpha (FRα)-positive ovarian cancer. These findings will be highlighted in three posters at the European Society for Medical Oncology (ESMO) Congress in Paris, France.

ANALYSES OF PATIENT-REPORTED OUTCOMES WITH MIRVETUXIMAB SORAVTANSINE VERSUS STANDARD CHEMOTHERAPY IN THE RANDOMIZED PHASE 3 FORWARD I STUDY IN OVARIAN CANCER (GOG 3011)
Lead Author: Kathleen N. Moore, MD
Date/Time: September 11, 2022, 12:00 – 1:00 PM CEST / 6:00 – 7:00 AM ET
Poster: #532P

The Phase 3 FORWARD I trial enrolled 366 patients who were randomized 2:1 to receive either mirvetuximab or the physician's choice of single-agent chemotherapy (pegylated liposomal doxorubicin, topotecan, or weekly paclitaxel). Eligible patients were diagnosed with platinum-resistant ovarian cancer that expresses medium or high levels of FRα and were treated with up to three prior regimens. The primary endpoint was progression-free survival (PFS), which was assessed in the entire study population and in the subset of patients with high FRα expression. Patients completed PRO assessments during screening, on day 1 of cycle 1, every 9 weeks thereafter (±1 week) until disease progression, and at the end of treatment visit.

Key findings:

• In the intent-to-treat (ITT) population, a statistically significant improvement in the number of patients achieving a 15-point improvement in gastrointestinal (GI) symptoms was observed at week 8/9 in patients treated with mirvetuximab versus chemotherapy (31.7% vs 14.0% P = 0.0162).
• The likelihood of GI symptom deterioration was 70% lower with mirvetuximab in the ITT population compared with chemotherapy (95% CI, 0.15–0.60; P=0.0007).
• In the FRα-high population, the likelihood of GI symptom deterioration was 80% lower with mirvetuximab compared with chemotherapy (95% CI, 0.10–0.54; P=0.0007).
• In both the ITT and FRα-high patient populations, improvements were seen with mirvetuximab compared with chemotherapy across multiple side effects, including sexuality, hair loss, pain severity, body image, and general improvement in ovarian cancer–specific symptoms.
• In both the ITT and FRα-high patient populations, there were statistically significant benefits in physical functioning for mirvetuximab over chemotherapy.

"An unmet need remains for safe, effective, and well-tolerated therapeutic options for patients with platinum-resistant ovarian cancer, despite treatment advancements seen in this setting," said Kathleen Moore, Director of the Oklahoma TSET Phase I Program, Professor of the Section of Gynecologic Oncology at The University of Oklahoma College of Medicine and FORWARD I Co-Principal Investigator. "The improved PROs associated with mirvetuximab compared to chemotherapy reinforce the differentiated tolerability profile of mirvetuximab and, coupled with its compelling anti-tumor activity and favorable safety, support its potential to serve as a new standard of care for patients with FRα-positive ovarian cancer."

EXPOSURE RESPONSE ANALYSIS FOR EFFICACY AND SAFETY OF MIRVETUXIMAB SORAVTANSINE IN PATIENTS WITH FOLATE RECEPTOR ΑLPHA-POSITIVE CANCER
Lead Author: Ursula A. Matulonis, MD
Date/Time: September 11, 2022, 12:00 -1:00 PM CEST / 6:00 – 7:00 AM ET
Poster: #592P

An ER analysis was conducted across three studies - the Phase 1 IMGN853-0401 trial, the Phase 3 FORWARD I trial, and the Phase 3 SORAYA trial - to understand the relationship between exposure to single-agent mirvetuximab and the efficacy and safety responses observed in patients with FRα-positive tumors.

Key findings:

• Both efficacy, in terms of objective response rate (ORR) and PFS, and ocular adverse events (AEs) were higher with increased exposure to mirvetuximab.
• These data highlight the importance of adherence to recommended mirvetuximab dosing guidelines in clinical practice.

POPULATION PHARMACOKINETIC ANALYSIS OF MIRVETUXIMAB SORAVTANSINE IN PATIENTS WITH FOLATE RECEPTOR ALPHA-POSITIVE CANCER
Lead Author: Kathleen N. Moore, MD
Date/Time: September 11, 2022, 12:00 – 1:00 PM CEST / 6:00 – 7:00 AM ET
Poster: #605P

A PK analysis, taking into account patient demographics and clinical characteristics, was conducted across three studies - IMGN853-0401, FORWARD I, and SORAYA - to understand the efficacy and safety of mirvetuximab in patients with FRα-positive tumors.

Key findings:

• Dosing adjustments do not appear to be necessary for patients with mild or moderate renal impairment or mild hepatic impairment.
• The analyses support the final recommended dose of 6 mg/kg based on adjusted ideal body weight (AIBW) every 3 weeks with balanced efficacy and safety.

Additional information can be found at www.esmo.org.

https://www.marketscreener.com/quote/stock/IMMUNOGEN-INC-9667/news/ImmunoGen-Presents-Additional-Analyses-Evaluating-Mirvetuximab-Soravtansine-in-Ovarian-Cancer-at-ESM-41747505/

Rise in Deaths Spurs Effort to Raise Alcohol Taxes

 Deaths caused by drinking also rose during the pandemic, spiking 25 percent in 2020 over the previous year. But the deaths — which have topped 140,000 nationwide — have been rising for decades in every state. Few places have seen a greater uptick than Oregon, where the rate of alcohol-induced deaths grew 2.5 times from 1999 to 2020, after adjusting for the state’s changing age distribution.

Ms. Grove’s only son, Jonathon, had begun drinking excessively in college, she said, but managed to work as a pharmacy tech for years at Oregon Health Sciences University despite his worsening addiction. Cheap beer and white wine were his weaknesses. “He always thought that he wasn’t drinking hard alcohol, so he wasn’t really an alcoholic,” Ms. Grove said. He died in a cheap hotel, surrounded by empty cans and containers.

Various studies in recent years have suggested that even moderate drinking poses a health risk, including to the heart. The Centers for Disease Control and Prevention recommends that men consume no more than two drinks a day and women no more than one.

Dr. Eric Roth, chief of emergency medicine at Kaiser Permanente’s two hospitals in the Portland area, estimated that 10 percent to 30 percent of his patients had illnesses or injuries at least partly linked to drinking. “It’s always been a big problem,” he said, “and it’s getting to be an increasingly big problem.”

To address substance abuse, Oregon has emphasized education and treatment to address substance use. A ballot measure passed in 2020 that decriminalized possession of small amounts of all drugs also diverted hundreds of millions of tax dollars from marijuana to recovery services, including for alcohol. This summer, Oregon sponsored a campaign to “Rethink the Drink.”

Dr. Tim Naimi, director of the Canadian Institute for Substance Use Research at the University of Victoria, labeled educational campaigns a “fig leaf” and said that treatment, while helpful, was akin to parking an ambulance beneath a cliff rather than fencing the precipice to prevent people from falling. Measures to prevent excessive drinking are less costly and more effective, he said. “If you want to talk prevention, you’ve got to talk policies.”.

https://yankeereporter.com/health/rise-in-deaths-spurs-effort-to-raise-alcohol-taxes/

Stress and depression are better long Covid indicators than physical comorbidities: study

 Studies have repeatedly suggested that physical conditions like immunosuppression and hypertension can increase a person’s risk not only for severe Covid but also long Covid. But in a new study, researchers found that psychological stressors such as depression, anxiety, and loneliness were more predictive of Covid patients’ likelihood of experiencing long Covid than classically associated physical factors.

“Unfortunately, there’s a long history of people not taking these conditions as seriously as they might take physical health conditions that might be easier to measure or easier to see,” said Andrea Roberts, a senior research scientist at the Harvard T.H. Chan School of Public Health and the senior author on the study, which was published Wednesday in JAMA Psychiatry. “For long Covid, obviously, then, it becomes very important to look at psychological health, and it raises more broadly the question of the importance of identifying and treating mental health issues.”

The study followed more than 54,000 survey respondents, most of whom were past or present health care workers, for 19 months starting in April 2020. At the beginning of the pandemic, these survey respondents self-assessed the amount of worry they felt about Covid-19, as well as the frequency of depressive or anxiety symptoms as a baseline measure. Non-health care workers were also assessed on their feelings of loneliness or perceived stress.

Researchers used surveys to follow up with the participants to determine whether they had tested positive for Covid; the researchers also identified those who experienced long Covid, defined as four weeks or more of symptoms. Almost 3,200 of the participants eventually contracted Covid. The researchers found that depression, anxiety, perceived stress, loneliness, and worry about the disease were associated with a 1.3- to 1.5-fold increase in risk for reporting long Covid symptoms. Participants reporting two or more types of distress had nearly a 50% increased risk for long Covid.

While the authors suggest biological mechanisms that might link mental health to long Covid symptoms, the study cannot show that stress or anxiety cause the disease. “This is an observational study, not a randomized clinical trial,” said Siwen Wang, a research fellow at Harvard and the study’s lead author. “Under a randomized clinical trial you will say ‘A’ is causal with ‘B.’ But for observational studies, we definitely cannot say for sure ‘this is a causal link that we find’; we only find association but not causal [relationships].”

Nonetheless, Aric Prather, a psychology and behavioral sciences professor at the University of California, San Francisco, who was not involved in the study, called the authors’ endeavors to account for possible confounding factors for long Covid “quite convincing.”

The researchers used three refinement models, first controlling for demographic factors (age, sex, racial identity, health care worker status, and partner’s education), then adjusting for factors like smoking and body mass index, then finally controlling for other common comorbidities including diabetes, hypertension, high cholesterol, asthma, and cancer. In each case, the relationship between prior psychological distress and long Covid remained strong.

Furthermore, of the participants who reported long Covid symptoms, the ones who had reported prior symptoms of psychological distress at the beginning of the pandemic were more likely to have long Covid symptoms severe enough to affect their daily ability to function than those who did not report psychological distress before contracting the disease.

The authors emphasized that these results should not suggest that long Covid symptoms are psychological.

“Often, ‘it’s all in your head’ is another way to say ‘we don’t know what’s going on,’” said Roberts, referring to the way in which clinicians’ dismissal of long Covid symptoms can blame the victim.

In the paper, Roberts and her colleagues pointed to multiple indicators that long Covid is not simply psychosomatic. Besides the fact that more than 40% of respondents did not report psychological distress in the baseline report, long Covid symptoms are also markedly different from mental illness symptoms.

The self-reported nature of both the initial psychological stressors and positive Covid tests injects uncertainty into the study design, but Wang noted that several validation studies show that self-reported health information from health care workers such as the ones surveyed have high validity.

Wang, Roberts, and Prather all pointed out that the survey data were taken from a cohort of predominantly white and predominantly female respondents (96.5% and 96.6%, respectively, of the original 54,960 respondents) and that until the research is replicated in more populations, it’s unknown whether the results can be generalized. However, Roberts noted that they saw the same trends with even stronger associations in the small number of men in the study.

To Wang, the surprising finding that mental stressors were a better indicator of long Covid risk than physical comorbidities is “signal” to health care workers and policymakers that mental health care should be better — and more accessible — for those who need it.

Prather agreed, saying this study shows that “lived experience” and mental health stressors are an important determinant of “who ends up getting sick and who ends up staying sick.”

“It’s a really great first step in this work and taking advantage of this large-scale data,” said Prather. “But obviously, it’s just the beginning of uncovering this story to really get to, more precisely, the factors that are at play.”

https://www.statnews.com/2022/09/07/stress-depression-better-long-covid-indicators-than-physical-comorbidities-study/

Biden Admin Is Placing Vending Machines Filled With Drug Supplies in Rural KY

 The Biden administration is set to spend $3.6 million to deploy vending machines filled with drug supplies in rural Kentucky—an effort the Biden administration claims will reduce stigma for drug users.

The project from the National Institutes of Health was launched in August and will study the effectiveness of "harm reduction kiosks" in rural Appalachia that contain "injection equipment, naloxone, fentanyl test strips, hygiene kits, condoms, and other supplies." The vending machines allow drug users to obtain items such as syringes without interacting with a health professional, in hopes of eliminating the "stigma" that comes with visiting an in-person harm reduction facility, according to the health agency.

The White House referenced the project in an August 31 press release on its actions taken "to address addiction and the overdose epidemic." The administration has adopted a wide range of harm reduction policies, which aim to make illicit drug use safer rather than eliminate it.

The Washington Free Beacon in February reported that the Department of Health and Human Services was set to fund the distribution of crack pipes through a $30 million harm reduction grant program. The administration backed off the funding plans amid public backlash, and the New York Times reported that the uproar over plans to fund crack pipes "derailed" Biden's drug policy agenda. The White House, however, still appears willing to adopt controversial harm reduction policies—the New York Times reported in July that Biden's drug czar Dr. Rahul Gupta was supportive of legalized injection sites, which allow users to take drugs with supervision from health professionals.

The new study, which is conducted by the University of Kentucky, appears to be the first effort from the federal government to deploy harm-reduction vending machines. Harm reduction vending machines have been popularized in Canada, Australia, and other countries. A few U.S. states, including New York, Rhode Island, Ohio, and Nevada, have deployed the machines in recent years. The machines sometimes include smoking kits, which in many cases include crack pipes.

The University of Kentucky declined to comment, directing the Free Beacon‘s inquiry to the NIH. The National Institute on Drug Abuse, which heads the project at the NIH, told the Free Beacon that along with drug paraphernalia, the vending machines will include "food kits, water, socks and gloves, feminine hygiene products, wound care, and resources/guides." The agency did not respond to questions regarding the status of the kiosk program.

https://freebeacon.com/biden-administration/biden-admin-is-placing-vending-machines-filled-with-drug-supplies-in-rural-kentucky/

All COVID-19 infections include a wide mix of SARS-CoV-2 virus variants

 Researchers at Case Western Reserve University found wide genetic variation in SARS-CoV-2 viruses among 360 patients whose viral infections were genetically sequenced, showing that all individual infections include multiple variants of the virus.

The researchers noted that reporting about the virus usually highlights a single dominant strain, which leads to under-reporting virus genetic variation and can have serious consequences in public-health planning and response.

“Our work brings attention to the complexity of infectious diseases that is often over-simplified when considering only the most abundant virus in an infection, and we demonstrate the importance of examining the variations that are historically considered noise,” said Ernest (Ricky) Chan, director of the bioinformatics core with the Cleveland Institute for Computational Biology at the Case Western Reserve School of Medicine. “We see that genetic variants observed in low frequency in SARS-CoV-2 infections can be early indicators of new strains responsible for later transmission surges.”

The paper, “COVID-19 Infection and Transmission Includes Complex Sequence Diversity,” will be published on September 8, 2022 in PLOS Genetics. {Embargoed for 9.8 at 2pm ET.) 

The CWRU team performed full genome sequencing of SARS-CoV-2 viruses from 250 patients in Northeast Ohio and used similar data from another 110 patients with full genetic sequences of infecting viruses provided through international research collaborators.

These data were developed in the early days of the COVID-19 pandemic when the Alpha variant and then the Delta variant were of major concern. This work showed that mutations found in Omicron BA.1 and BA.2 were already present as relatively minor variations at least a year before Omicron and its many iterations became “variants of concern.” Omicron and its own variants were central to a major COVID-19 resurgence last winter. 

“Concentration on a majority consensus of virus variants within the global research community diverts attention from genetic variation that may contribute significantly to the continuing evolution of the COVID-19 pandemic,” said Peter Zimmerman, a professor in the Department of Pathology at the School of Medicine. {EMBED LINK TO BIO} “Focus on majority variants is a critical first step in development of diagnostics, therapeutics and vaccines, however the research community needs to quantify and report out variation, so that the public health community and the general public are better prepared and nimble in response to the ever-evolving virus.”   

Much continues to be made to define and track the emergence of virus lineages across the ongoing evolution of SARS-CoV-2 around the world. In the interest of time, global researchers have been relying on tracking and reporting on relatively dominant variations. But the CWRU researchers noted that, given the multiple variations within single infections, it is important to report a more complete representation of the viral genetic sequences to understand how these genetic changes can spread and potentially interact with different categories of patient conditions, including evasion from eradication efforts. 

JOURNAL

PLoS Genetics

SUBJECT OF RESEARCH

Cells

ARTICLE TITLE

COVID-19 infection and transmission includes complex sequence diversity

ARTICLE PUBLICATION DATE

8-Sep-2022

https://www.eurekalert.org/news-releases/964086

SpringWorks Data from Phase 3 at ESMO

 – Nirogacestat Treatment Resulted in Rapid, Sustained and Statistically Significant Improvements in Primary and All Key Secondary Efficacy Endpoints –

– NDA Submission to the U.S. FDA Planned for Second Half of 2022; Application to be Submitted for Review Under the FDA’s Real-Time Oncology Review Program (RTOR) –

– Company to Host Virtual Investor Event on Sunday, September 11 at 10:00 a.m. ET (4:00 p.m. CEST) –

ESMO Oral Presentation Details   

Title: DeFi: A Phase 3, Randomized Controlled Trial of Nirogacestat Versus Placebo for Progressing Desmoid Tumors (DT)
Presentation Number: LBA2
Presenter: Bernd Kasper, M.D., Ph.D., University of Heidelberg, Mannheim Cancer Center, Mannheim, Germany
Session/Type: Presidential Symposium 1, Proffered Paper Session
Date: Saturday, September 10, 2022
Time: 4:55-5:10 p.m. CEST (10:55-11:10 a.m. ET)

Investor Event Details

Presenters: SpringWorks’ management team will be joined by Bernd Kasper, M.D., Ph.D., University of Heidelberg, Mannheim Cancer Center, Mannheim, Germany and Principal Investigator of the DeFi trial.
Date: Sunday, September 11, 2022
Time: 4:00 p.m. CEST (10:00 a.m. ET)
Instructions: To join the live webcast and view corresponding slides, please visit the Events & Presentations page within the Investors & Media section of the Company’s website at https://ir.springworkstx.com. To join via audio teleconference, please register here. Once registration is complete, participants will be provided with a dial-in number and conference code to access the call. A replay will be available on the Company’s website for a limited time following the event.

https://www.marketscreener.com/quote/stock/SPRINGWORKS-THERAPEUTICS-65542668/news/SpringWorks-Therapeutics-Announces-Data-from-Phase-3-DeFi-Trial-Evaluating-Nirogacestat-in-Adult-Pat-41738859/

Potential Problem(s) With a Once-a-Year COVID Vaccine

 Comments from the White House this week suggesting a once-a-year COVID-19 shot for most Americans, "just like your annual flu shot," were met with backlash from many who say COVID and influenza come from different viruses and need different schedules.

Remarks, from "capitulation" to too little data, hit the airwaves and social media.

Some, however, agree with the White House vision and say that asking people to get one shot in the fall instead of periodic pushes for boosters will raise public confidence and buy-in and reduce consumer confusion.  

Health leaders, including Bob Wachter, MD, chair of the Department of Medicine at the University of California San Francisco, say they like the framing of the concept — that people who are not high-risk should plan each year for a COVID shot and a flu shot.

"Doesn't mean we KNOW shot will prevent transmission for a year. DOES mean it'll likely lower odds of SEVERE case for a year & we need strategy to bump uptake," Wachter tweeted this week.

But the numbers of Americans seeking boosters remain low. Only one-third of all eligible people 50 years and older have gotten a second COVID booster, according to the Centers for Disease Control and Prevention (CDC). About half of those who got the original two shots got a first booster.

Meanwhile, the United States is still averaging about 70,000 new COVID cases and more than 300 deaths every day.

The suggested change in approach comes as Pfizer/BioNTech and Moderna rolled out their new boosters that target Omicron subvariants BA.4 and BA.5 after the CDC recommended their use and the US Food and Drug Administration approved emergency use authorization.   

"As the virus continues to change, we will now be able to update our vaccines annually to target the dominant variant," President Joe Biden said in a statement promoting the yearly approach.

Some Say Annual Shot Premature

Other experts say it's too soon to tell whether an annual approach will work.

"We have no data to support that current vaccines, including the new BA.5 booster, will provide durable protection beyond 4 to 6 months. It would be good to aspire to this objective, and much longer duration or protection, but that will likely require next generation and nasal vaccines," said Eric Topol, MD, Medscape's editor-in-chief and founder and director of the Scripps Research Translational Institute.

A report in Nature Reviews Immunology last month states, "Mucosal vaccines offer the potential to trigger robust protective immune responses at the predominant sites of pathogen infection" and potentially "can prevent an infection from becoming established in the first place, rather than only curtailing infection and protecting against the development of disease symptoms."

Topol tweeted after the White House statements, "(An annual vaccine) has the ring of Covid capitulation."

William Schaffner, MD, an infectious disease expert at Vanderbilt University School of Medicine in Nashville, Tennessee, told Medscape Medical News that he cautions against interpreting the White House comments as official policy.

"This is the difficulty of having public health announcements come out of Washington," he said. "They ought to come out of the CDC."

He says there is a reasonable analogy between COVID and influenza, but warns, "don't push the analogy."

They are both serious respiratory viruses that can cause much illness and death in essentially the same populations, he notes. These are the older, frail people, people who have underlying illnesses or are immunocompromised.

Both viruses also mutate. But there the paths diverge.

"We've gotten into a pattern of annually updating the influenza vaccine because it is such a singularly seasonal virus," Schaffner said. "Basically it disappears during the summer. We've had plenty of COVID during the summers."

For COVID, he said, "We will need a periodic booster. Could this be annually? That would certainly make it easier." But it's too soon to tell, he said.

Schaffner noted that several manufacturers are working on a combined flu/COVID vaccine.

Just a "First Step" Toward Annual Shot

The currently updated COVID vaccine may be the first step toward an annual vaccine, but it's only the first step, Schaffner said. "We haven't committed to further steps yet because we're watching this virus."

Syra Madad, DHSc, MSc, an infectious disease epidemiologist at Harvard University's Belfer Center for Science and International Affairs and the New York City hospital system, told Medscape Medical News that arguments on both sides make sense.

Having a single message once a year can help eliminate the considerable confusion involving people on individual timelines with different levels of immunity and separate campaigns for COVID and flu shots coming at different times of the year.

"Communication around vaccines is very muddled and that shows in our overall vaccination rates, particularly booster rates," she says. "The overall strategy is hopeful and makes sense if we're going to progress that way based on data."

However, she said that the data are just not there yet to show it's time for an annual vaccine. First, scientists will need to see how long protection lasts with the Omicron-specific vaccine and how well and how long it protects against severe disease and death as well as infection.

COVID is less predictable than influenza and the influenza vaccine has been around for decades, Madad noted. With influenza, the patterns are more easily anticipated with their "ladder-like pattern," she said. "COVID-19 is not like that."

What is hopeful, she said, "is that we've been in the Omicron dynasty since November of 2021. I'm hopeful that we'll stick with that particular variant."

Topol, Schaffner, and Madad declared no relevant financial relationships.

https://www.medscape.com/viewarticle/980540