Novartis is ceasing development of NIS793, am anti-TGFß monoclonal antibody licensed from XOMA for pancreatic cancer and other oncologic.conditions.
Friday, August 25, 2023
Brain disease biotech Neumora Therapeutics files for an estimated $250 million IPO
Neumora Therapeutics, a Phase 3 biotech developing therapies for brain diseases, filed on Friday with the SEC to raise up to $100 million in an initial public offering. However, this is likely a placeholder for a deal we estimate could raise up to $250 million.
The company's pipeline consists of seven clinical and preclinical neuroscience programs that target novel mechanisms of action for a broad range of underserved neuropsychiatric disorders and neurodegenerative diseases. Its lead candidate, navacaprant (NMRA-140), is a novel once-daily oral kappa opioid receptor (KOR) antagonist that is being developed for the treatment of major depressive disorder (MDD), which the company believes has the potential to provide significant advantages relative to the standard of care, if approved. Neumora is initiating a pivotal Phase 3 program for navacaprant monotherapy in patients with moderate to severe MDD and anticipates releasing topline results for the first of three efficacy studies in the second half of 2024.
The Watertown, MA-based company was founded in 2019 and plans to list on the Nasdaq under the symbol NMRA. Neumora Therapeutics filed confidentially on November 8, 2021. J.P. Morgan, Stifel, RBC Capital Markets, and William Blair are the joint bookrunners on the deal. No pricing terms were disclosed.
Subclinical Afib Caught on Cardiac Devices Might Be Better Left Alone
Edoxaban (Savaysa) didn't improve outcomes for high-risk patients with subclinical atrial fibrillation (Afib)-like episodes detected by implanted cardiac devices, the NOAH-AFNET 6 trial showed.
The direct oral anticoagulant (DOAC) yielded a 3.2% per patient-year rate of the primary composite endpoint of cardiovascular death, stroke, or systemic embolism, similar to the 4.0% per patient-year rate with a no-anticoagulation placebo (HR 0.81, 95% CI 0.60-1.08, P=0.15).
Strokes occurred in about 1% of patients in both groups, Paulus Kirchhof, MD, of the University Heart and Vascular Center Hamburg in Germany, reported here at the European Society of Cardiology (ESC) Congress.
The results were also published in the New England Journal of Medicine
And, as expected, edoxaban led to an excess in the composite risk of all-cause mortality or major bleeding compared with placebo (5.9% vs 4.5% per patient-year, HR 1.31, 95% CI 1.02-1.67, P=0.03).
"We think that we have good news for our patients with atrial high-rate episodes [AHREs]," Kirchhof said at a press conference where the findings were discussed. "This trial demonstrates that anticoagulation should not be used in patients with atrial high-rate episodes until atrial fibrillation is documented by ECG. And that is a practice-changing finding, at least for many clinicians."
The cardiac electrical activity recorded during these AHREs looks like the activity recorded during Afib, and indeed 97% of the episodes were over 200 bpm with a median duration of nearly 3 hours. Presuming that this would contribute to stroke risk, some clinicians have initiated oral anticoagulant therapy, particularly for high-stroke-risk patients and for those with long-lasting AHREs.
"Will this change the guidelines?" posited ESC study discussant Elena Arbelo, MD, PhD, of the University of Barcelona. "I think the guidelines nowadays just recommend asking for ECG documentation of the arrhythmias. I think this will need to stay this way, and we must be careful indicating anticoagulation without ECG documentation."
Press conference moderator Martin Halle, MD, of the Technical University of Munich, noted that "we all expected a different result here. This is clearly changing also the mind on pathophysiology and also the way we think of how emboli develop in the left atrium," setting up further research needs.
The event-driven trial fully enrolled with 2,536 patients ages 65 and older (mean age 78 years, 37.4% women) before it was terminated early at a median follow-up of 21 months "on the basis of safety concerns and the results of an independent, informal assessment of futility," the researchers noted.
Enrollment required AHREs (an atrial rate of ≥170 bpm as captured on a pacemaker, defibrillator, resynchronization device, or implanted loop recorder capable of long-term rhythm monitoring) lasting for at least 6 minutes and at least one additional risk factor for stroke but no history of clinical Afib on electrocardiogram. Median CHA2DS2-VASc score was 4.
Participants were randomly assigned to double-blind, double-dummy treatment with edoxaban at standard doses for Afib or placebo with aspirin according to clinical indications (which 54% received).
The researchers noted that stopping early after the accrual of 184 of the 220 originally planned primary efficacy outcome events left the trial with insufficient power to detect or rule out a small beneficial effect of oral anticoagulation on the prevention of stroke, which occurred at a lower rate than expected from prior trials.
Limitations also included the trial population of predominantly white patients in Europe.
Generalizability to other DOACs was unclear, Kirchhof cautioned. There are other trials underway, notably the ARTESiA trial with apixaban for device-detected sub-clinical Afib, which is due to report results soon.
Another big question clinically is how to address atrial arrhythmias as detected by consumer wearables when no Afib is documented on an ECG.
"With these results, we may speculate that we need also to be cautious" in prescribing anticoagulation in that setting, Arbelo added.
While acknowledging that more data are coming, Kirchhof told MedPage Today at a press conference that there's no reason to wait to act. "I do think that it is time to change practice, because we didn't have evidence before and now we have evidence. Whether the conclusion coming from our data is the same that we'll see in 3 or 4 years time is hard to predict, but I do think we have a robust trial. We have a clear signal for harm."
Disclosures
The trial was supported by the German Ministry of Education and Research through the German Center for Cardiovascular Research and by Daiichi Sankyo Europe.
Kirchhof disclosed that he has research funding from "several drug and device companies active in atrial fibrillation and has received honoraria from several such companies in the past, but not in the last 3 years." He has two patents for atrial fibrillation therapy and markers held by his university.
Arbelo disclosed relationships with Biosense Webster.
Primary Source
New England Journal of Medicine
Source Reference: Kirchhof P, et al "Anticoagulation with edoxaban in patients with atrial high-rate episodes" N Engl J Med 2023; DOI: 10.1056/NEJMoa2303062.
Information regarding Oncopeptides’ appeal of U.S. withdrawal published
On August 25, 2023, more information regarding the formal request from the U.S. Food and Drug Administration (FDA) to voluntarily withdraw Pepaxto's approval in the U.S has been made available by the FDA.
The public docket contains, among other documents, a detailed appeal document outlining Oncopeptides' arguments for why Pepaxto should remain on the U.S. market as an important treatment option for multiple myeloma patients in later lines of treatment.
“Our OCEAN study demonstrated clinical benefit for multiple myeloma patients, in particular for non-transplanted elderly patients where the unmet medical need remains very high, and we remain confident that it would provide value for patients all over the world, including the U.S.,” says Sofia Heigis, CEO of Oncopeptides. “We value the opportunity to share our perspective and look forward to a continued dialogue with the FDA.”
Investor Q&A
What does this mean for Oncopeptides?
The FDA has published certain documents regarding the appeal process that Oncopeptides informed the market about on August 10. The information in the documents have been communicated before, and the foundational fact remains the same: the FDA is still looking to withdraw the approval of Pepaxto from the U.S. market, a decision which we have appealed.
Why didn´t you communicate these documents sooner?
We adhere to the appeals process, which is led by the FDA. We aim to keep the market and other key stakeholders informed as far as possible while still respecting the process.
Could you estimate the chance of success of this appeal?
We don´t want to speculate on that. While our strong confidence in the product and its ability to help patients suffering from Multiple Myeloma also in the U.S. remains, we need to remember that we currently don´t market Pepaxto in the U.S.
Oncopeptides’ full strategic focus is on the product roll-out in Europe, where we have a marketing authorization and an established marketing company.
I have questions about the contents of the appeal document that you have filed
Reach out to David Augustsson, Director of Corporate Affairs at david.augustsson@oncopeptides.com
I have questions about the continued FDA appeal process
At this time we cannot share any more details or information other than what is made public by the FDA through the following links:
https://www.federalregister.gov/public-inspection/2023-18320/withdrawal-of-approval-of -new-drug-application-pepaxto-equivalent-to-20-milligrams-base-per-vial
https://www.regulations.gov/docket/FDA-2023-N-3167
We aim to keep the market and other key stakeholders informed as far as possible while still respecting the formal process.
After Backlash, Feds Cancel Plan That Risked Limiting Breast Reconstruction Options
Federal regulators have abandoned a plan that physicians, patients, and advocacy groups for breast cancer patients feared would limit women’s options for reconstructive surgery.
The controversy centered on how doctors are paid for a type of breast reconstruction known as DIEP flap, in which skin, fat, and blood vessels are harvested from a woman’s abdomen to create a new breast.
Last year, the Centers for Medicare & Medicaid Services decided to eliminate a trio of medical billing codes for breast reconstructive surgery that enabled doctors to collect much more money for DIEP flap operations than for simpler types of breast reconstruction. Some plastic surgeons said the government’s move would limit access and make DIEP flaps available only to those who could afford to pay tens of thousands of dollars out-of-pocket.
Through its coding decisions, the federal government can influence the medical options available to patients, even those with private insurance.
In an Aug. 22 memo, CMS wrote that it received a “substantial number of responses” verbally and in writing asking regulators to keep the “S” billing codes that reimburse doctors more for the surgery. “The majority of the commenters feel their accessibility will be, or has already been, impacted by the decision to eliminate the S codes,” the agency wrote in reversing its earlier plan.
Supporters praised CMS’ latest action. “I’m so grateful to CMS for this decision that is really meaningful,” Elisabeth Potter, a plastic surgeon who specializes in DIEP flap surgeries, said in a social media post.
The agency’s announcement came after it convened a public hearing in June, during which several patients, physicians, and representatives of breast cancer advocacy organizations implored CMS officials to scrap their original plan. Otherwise, they said, access to DIEP flap surgery would diminish.
The DIEP flap procedure has potential benefits over implants and operations that take muscle from the abdomen. For example, although implants are less costly and less time-intensive to perform, they generally need to be replaced every 10 years or so. But DIEP flap surgery is also more expensive. If patients go outside an insurance network for the operation, it can cost more than $50,000. A plastic surgeons’ group argued some in-network doctors would stop offering the surgery if insurers paid significantly less.
“This decision is monumental for breast cancer patients and breast reconstruction,” Christy Huling, who had a double mastectomy and DIEP flap surgery, said during CMS’ June 1 meeting. Through tears, Huling said she is an avid outdoors person and that her life would have changed “drastically” if she’d instead had reconstruction surgery that removed muscle from her abdomen. “This procedure has allowed me to continue to maintain my quality of life,” she said of DIEP flap.
The government’s initial plan was driven by the Blue Cross Blue Shield Association, a major lobbying organization for health insurance companies. In 2021, the group asked CMS to discontinue the three S codes, arguing they were no longer needed, according to a CMS document.
CMS initially decided the codes would expire at the end of 2024; however, even with the delayed effective date, physicians said, the decision was starting to hinder access to DIEP flap surgery and create anxiety for patients. At least two major insurance companies told doctors they would no longer reimburse them under the higher-paying codes.
A bipartisan group of lawmakers also protested, including Rep. Debbie Wasserman Schultz (D-Fla.) and Sen. Amy Klobuchar (D-Minn.), who have both had breast cancer; Rep. James Comer (R-Ky.); and Sen. Marsha Blackburn (R-Tenn.). “This latest CMS decision will provide women with more certainty, and help ensure fair and equitable access to their choice of breast reconstruction techniques,” Wasserman Schultz said in a statement following CMS’ change.
Codes don’t dictate the amounts private insurers pay for medical services; those reimbursements are generally worked out between insurance companies and medical providers. However, using the targeted S codes, doctors and hospitals have been able to distinguish DIEP flap surgeries, which require complex microsurgical skills, from other forms of breast reconstruction that take less time to perform and generally yield lower insurance reimbursements.
CMS’ initial plan would have made it “impossible to continue doing high-volume, high-quality complex breast microsurgery for breast cancer patients,” Dhivya Srinivasa, a plastic surgeon in California who specializes in breast reconstruction, said during CMS’ June 1 hearing. “I am already seeing it, patients who are good candidates who were told ‘no.’ Why were they told no when they’re a good candidate? To say that it has nothing to do with reimbursement, I think, would be foolish.”
https://kffhealthnews.org/news/article/cms-ruling-diep-flap-breast-reconstruction/
Canadian Wildfire Smoke Increased Asthma-Related ED Visits in the U.S.
Exposure to smoke originating from the Canadian wildfires led to a rise in asthma-associated emergency department (ED) visits in the U.S., with a large spike seen in New York during days with the highest recorded pollution, CDC data showed.
Asthma-related ED visits across the U.S. were 17% higher than expected during the 19 days with wildfire smoke that occurred from April 30 to August 4, reported Cristin McArdle, PhD, of the CDC's Epidemic Intelligence Service and the National Center for Environmental Health, and colleagues in the Morbidity and Mortality Weekly Report.
A simultaneously published report
also showed that daily mean concentrations of particulate matter with aerodynamic diameter ≤2.5 µm (PM2.5) were highest on June 7 for all regions in New York, except the Adirondacks, leading to an 81.9% increase in asthma-associated ED visits statewide compared with the mean number of ED visits during June 1-5, according to Haillie Meek, DVM, of the New York State Department of Health and CDC's Epidemic Intelligence Service, and colleagues.
Reached for comment, Alison Lee, MD, of the Icahn School of Medicine at Mount Sinai in New York City, suggested that high-risk groups consider protective measures on days where the air quality is worse.
"If you fall into a sensitive group, wearing a well-fitted mask -- an N95 or KN95 mask -- can help filter out some of those particulates," she told MedPage Today. "Staying indoors and making sure that you have good air filtration is also important on those days where the air quality is poor."
Lee noted as well that Wildfires can no longer be thought of as isolated events, and they can cumulatively begin to affect healthy populations as well.
"These fires have been burning almost continuously," she said. "So then we're talking about a situation where it's not bad air quality on one day, but rather repeated events, multiple-day or multiple-week exposures to poor air quality. I think then you'll have the potential to see health impacts on otherwise healthy groups."
With the possibility of wildfires being more common, more research needs to be conducted on the potential health impacts, including long-term effects, she added, and clear guidelines regarding the Air Quality Index (AQI) should be released.
U.S. Study
The report by McArdle and team showed that the HHS-defined regions most affected by the wildfire smoke were Regions 2 (New Jersey, New York, Puerto Rico, and the U.S. Virgin Islands), 3 (Delaware, District of Columbia, Maryland, Pennsylvania, Virginia, and West Virginia), and 5 (Illinois, Indiana, Michigan, Minnesota, Ohio, and Wisconsin). Region 3 had five wildfire smoke event days, while regions 2 and 5 had four days each.
Wildfire smoke event days are defined at the HHS region level as "when at least one Environmental Protection Agency (EPA) air quality monitor in the region measures ambient 24-hour average PM2.5 concentrations ≥35.5 µg/m3, corresponding to the EPA AQI value of 101." An AQI of 101-150 is considered to be "unhealthy for sensitive groups," 150-200 is "unhealthy," 200-301 is "very unhealthy," and anything above 301 is considered "hazardous."
Region 2 had the biggest increase in asthma-associated ED visits, with higher-than-expected visits occurring for all age groups on 2 days from June 6-8, representing 364 excess visits. Region 3 had 179 excess asthma-associated ED visits across all age groups, and region 5 had 172 excess visits. When broken down by age, patients ages 18-64 experienced the greatest number of excess visits across all three regions.
Other regions experiencing higher-than-expected asthma-associated ED visits included Regions 4 (Alabama, Florida, Georgia, Kentucky, Mississippi, North Carolina, South Carolina, and Tennessee), 8 (Colorado, Montana, North Dakota, South Dakota, Utah, and Wyoming), and 10 (Alaska, Idaho, Oregon, and Washington).
New York Study
Narrowing in on New York, a total of 1,310 asthma-associated ED visits occurred from June 1-14, as recorded in the New York State Department of Health's Electronic Syndromic Surveillance System, which includes the 134 EDs in New York excluding New York City. The largest region-specific increases in asthma-associated ED visits occurred in the Eastern Lake Ontario (179.1%), Central (132.8%), and Upper Hudson Valley (86.4%) regions.
There were increases in asthma-related ED visits across several age groups, with an increase of 197.6% in those ages 10-29, an increase of 89% in those ages 50-69, 77.1% in those ages 30-49, and 76.5% in those 70 and older. Children ages 0-9 years saw a 7.4% decrease in visits.
McArdle and colleagues highlighted the role of climate change in the risk of wildfire smoke exposure. Research has indicated that climate change is already impacting wildfires, with increased temperatures, more dry seasons, and longer wildfire seasons, leading to situations like the Canadian wildfires becoming more common.
According to Lee, "until we act to impact climate change, these wildfires are going to continue to be concerns we will have to face. ... I think we really need to think about how we can push our politicians and our representatives to try to tackle climate change. Until we do that, this wildfire smoke is just going to get worse."
Disclosures
McArdle, Meek, and Lee reported no conflicts of interest.
One co-author reported relationships with the European Respiratory Society and the Career Mentoring Committee of the American College of Epidemiology.
Primary Source
Morbidity and Mortality Weekly Report
Source Reference: McArdle CE, et al "Asthma-associated emergency department visits during the Canadian wildfire smoke episodes -- United States, April-August 2023" MMWR 2023; DOI: 10.15585/mmwr.mm7234a5.
Secondary Source
Morbidity and Mortality Weekly Report
Source Reference: Meek HC, et al "Asthma-associated emergency department visits during a wildfire smoke event -- New York, June 2023" MMWR 2023; DOI: 10.15585/mmwr.mm7234a6.
Ob/Gyn Switching to Independent System for Residency Applications
Beginning next year, ob/gyn programs will start using an independent system for processing residency applications, rather than the Electronic Residency Application Service (ERAS).
The joint decision to switch to the new system was made by the American College of Obstetricians and Gynecologists (ACOG), the Association of Professors of Gynecology and Obstetrics (APGO), and the Council on Resident Education in Obstetrics and Gynecology (CREOG). The new system will be managed by Liaison International, which uses "Centralized Application Service (CAS) technology," according to the company's website.
A joint statement on the APGO website
said that the new system "will be user friendly and efficient, less expensive for applicants, and will directly decrease the burdens faced by program directors, program managers, and applicants alike," and "will incorporate the entirety of interview season functions, from application submission, review, interview offers and interviews, to rank list submission."
ACOG explained that the decision to pull the ERAS stemmed from the Right Resident, Right Program, Ready Day One initiative, noting that the new system is mobile-friendly and "will include immediate fee reduction," as detailed on their FAQ page.
In response, the Association of American Medical Colleges (AAMC), which runs ERAS and the Match, issued a statement attributed to President and CEO David J. Skorton, MD, and Alison J. Whelan, MD, the chief academic officer, saying they were "surprised and dismayed" by the decision. They also said the organization was worried about losing ob/gyn program data, which has been used for longstanding research and analytics.
"While it is too early to fully understand the consequences of this development -- intended and unintended -- the AAMC remains committed to creating a fair and equitable process for learners, medical schools, and programs," they wrote.
Bryan Carmody, MD, of Eastern Virginia Medical School in Norfolk, shared information about the change on social media, writing on his blog that ob/gyn program directors helped to pilot ERAS when it was first rolled out in the mid-90s.
Carmody told MedPage Today that he anticipates the biggest downsides will fall on applicants, such as those who want to apply to another specialty in addition to ob/gyn.
"Those applicants will have to use one system to apply to ob/gyn and another to their other specialty," he explained. "The same thing applies to applicants who fail to match. They'll have to use ERAS to apply to another specialty during SOAP [Supplemental Offer and Acceptance Program] since few, if any, ob/gyn positions are typically available."
Conversely, he pointed to "flexibility, customizability, better analytics, [and] more generous data sharing with programs from the sponsor" as potential benefits.
Other specialties, like ophthalmology and plastic surgery, have been using their own residency applications for years, but Carmody isn't sure if others will follow in the footsteps of ob/gyn.
"There's a lot of inertia that would have to be overcome. At the same time, I don't think many residency programs have any deep brand loyalty to ERAS. If applicants and ob/gyn programs have a good experience with the new system, it certainly could create momentum that would encourage other specialties to follow suit," he said.
Morgan Levy, a medical student in the MD/MPH program at the University of Miami Miller School of Medicine, is in the last class of prospective ob/gyn residents applying through ERAS. She said that the switch to a new system is the latest in a series of changes to the residency and Match process.
"I think there's been a pretty concerted effort by medical education leadership in all specialties to really reform the residency application process," she noted. "As these new interventions they're trying are working more and more, they're more and more compelled to adopt them in a way that suits their fields the best."
Applying for residency is already demanding, and Levy noted that some parts of the process have been distracting to fourth-year medical students who are also trying to make the most of their studies. She said some previous changes -- like universal interview dates and virtual interviews -- have helped to combat the added stress and made the process more equitable. Now, many students don't have to spend thousands of dollars traveling for interviews in addition to the cost of the applications themselves.
ACOG, APGO, and CREOG will release webinars with more information for applicants and program directors at a later date.
https://www.medpagetoday.com/special-reports/features/106067
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