In a poster titled "Cryoablation for the treatment of early-stage breast cancer in patients who decline surgery" Dr. Graña-López presented the findings of her study conducted at University Hospital Lucus Augusti in Lugo,Spainwhich used ProSense for cryoablation treatment of 31 patients with early-stage breast cancer who declined surgery, the standard of care. Dr. Graña-López, a radiologist who specializes in breast and women's imaging, is Head of the Breast Unit at University Hospital Lucus Augusti.
All patients were diagnosed with biopsy-proven early breast cancer (cT1-2cN0-1cM0) with a median tumor size of 24 mm, ranging between 6 to 45 mm. Patients were followed by mammography and ultrasound every 6 months for 2 years and annually thereafter. The median follow-up was 10 months, with a range of 0 to 40 months. Cancer progression was observed in 1 patient (1/31, 3.2%). No major complications were seen and the procedure was well tolerated by all patients.
The study concluded that cryoablation could be an alternative treatment to surgery for breast cancer in patients who reject surgery. Underscoring the need for such an alternative, the poster presented that breast cancer is the most commonly diagnosed malignant neoplasm worldwide and that while surgery is the standard of care for early-stage breast cancer, some patients, most of them elderly, decline standard of care surgery and prefer a less invasive option.
The Nobel Prize in Physiology or Medicine has been awarded to a pair of scientists who developed the technology that led to the mRNA Covid vaccines.
Professors Katalin Kariko and Drew Weissman will share the prize.
The technology was experimental before the pandemic, but has now been given to millions of people around the world to protect them against serious Covid-19.
The same mRNA technology is now being researched for other diseases, including cancer.
The Nobel Prize committee said: "The laureates contributed to the unprecedented rate of vaccine development during one of the greatest threats to human health in modern times."
Both were told they had won by telephone this morning and were said to be "overwhelmed".
In 2021, California Governor Gavin Newsom (D) vowed to replace any Senate vacancies with a black woman.
On Sunday, he did just that following the death of Sen. Dianne Feinstein (D), appointing the first black lesbian to ever openly serve in Congress.
Laphonza Butler, president of of pro-abortion organization EMILY's List who served as a senior adviser to Kamala Harris' very failed 2020 presidential campaign, and currently a resident of Maryland, was announced as Feinstein's replacement in a Sunday night announcement by Newsom.
Butler will finish Feinstein's term, which runs until 2024, after which she may face off with Rep. Adam Schiff (D-CA), who had been hoping Feinstein would live till the election so he could slide into the Senate.
"As we mourn the enormous loss of Senator Feinstein, the very freedoms she fought for — reproductive freedom, equal protection, and safety from gun violence — have never been under greater assault," said Newsom, adding "Laphonza will carry the baton left by Senator Feinstein, continue to break glass ceilings, and fight for all Californians in Washington D.C."
Butler was born in Magnolia, Mississippi, where she began her career as a union organizer. In 2009, she moved to California, where she served as president of SEIU United Long Term Care Workers, where she was instrumental in raising minimum wage, and hiking taxes on wealthy Californians. She also served as a University of California regent for three years, until she moved to Maryland in 2001.
After advising Kamala Harris on her 2020 campaign, Butler left SCRB strategies to become Airbnb's director of public policy and campaigns in North America. Wile working for Harris, she was hired by Uber during an organized labor dispute - when Harris's brother-in-law, Tony West, was Uber's chief legal officer.
Many have made light of the fact that Butler doesn't actually live in California.
The Naval Special Warfare (NSW) Command will begin randomly testing its personnel for performance-enhancing drugs (PEDs), following allegations that such drugs are in widespread use among the Navy's special warfare community.
Rear Adm. Keith Davids, the commander of NSW, announced the command will introduce incremental, random force-wide urinalysis testing starting in November.
“My intent is to ensure every NSW teammate operates at their innate best while preserving the distinguished standards of excellence that define NSW,” Rear Adm. Davids said in a Friday press statement.
NSW is most known for its Navy SEAL teams but the command is also responsible for training and deploying Special Warfare Combatant Crewmen and Explosive Ordnance Disposal technicians.
Illicit substances have been a persistent concern throughout the military, even in the special operations community. Some leaders have balked at testing regimens for performance-enhancing drugs because they are often highly specialized and costly and require contracting through a limited number of labs that do such work. The military services have done occasional tests when they perceive a problem with an individual service member, but they must get special permission from the Pentagon to do routine, random testing.
New Testing Regime Follows SEAL Training Death
The NSW's new random uranalysis regimen comes on the heels of an investigation into the 2022 death of 24-year-old SEAL candidate Kyle Mullen, during his Basic Underwater Demolition/SEAL course. The SEAL candidate collapsed and died of acute pneumonia just hours after completing the infamous "Hell Week" portion of the course.
A May 2023 investigative report (pdf) states that investigators uncovered a bottle of pills marked as sildenafil in Mr. Mullen's car following his death. Sildenafil is a substance used for erectile dysfunction treatments, but which can also be used to increase blood flow in strength training and can reduce the risk of swimmer’s induced pulmonary edema. Investigators also found vials labeled as testosterone and human growth hormone, and syringes.
It is unclear from the investigation whether Mr. Mullen used these PEDs, though it did determine that they were not the cause of his death. The investigation did find "strong indicators" of PED use among other members of Mr. Mullen's class.
"While SN Mullen’s death was not caused by PED use, PEDs use must be eliminated from NSWC and other high risk training," the command investigation states.
While these PEDs may give troops a competitive edge in the rigorous and highly selective special operations community, the command investigation states their use "creates significant, unquantified, and unmitigable risk to candidates going through the high intensity training."
Misuse of phosphodiesterase inhibitors—the class of pharmaceutical compounds that includes Sildenafil—can result in severe low blood pressure, cardiovascular collapse, and death. Other PEDs pose risks of kidney and liver dysfunction, strokes, heart attacks, blood clots in the lung vasculature, high blood pressure, mood swings, and a risk of contracting HIV or hepatitis from non-sterile needle use.
In addition to the health risks, the command investigation said PED use is also "contrary to the SEAL ethos and the Navy's core values."
The May investigative report recommended expanded PED screening regimens as one of several ways to improve safety within the various Naval Special Warfare training pipelines. The investigation also called for more careful screening and training of the staff overseeing Naval Special Warfare training, and reducing the stigma candidates face to avoid disclosing injuries.
"We will honor Seaman Mullen's memory by ensuring that the legacy of our fallen teammate guides us towards the best training program possible for our future Navy SEALs," Rear Adm. Davids said in May, at the conclusion of the command investigation.
Today, theU.S. Food and Drug Administrationgranted de novo marketing authorization for the Invitae Common Hereditary Cancers Panel, an in vitro diagnostic test that can help detect hundreds of genetic variants associated with an elevated risk of developing certain cancers. The test can also help identify potentially cancer-associated hereditary variants in individuals with already-diagnosed cancer. The test, which is the first of its kind to be granted FDA marketing authorization, evaluates DNA extracted from a blood sample to identify variants in 47 genes known to be associated with an elevated risk of developing certain types of cancer.
"This test can assess multiple genes in a single test by using next-generation sequencing, which has proven helpful in providing insight into genetic variants with sensitivity and speed," said Jeff Shuren, M.D., J.D., director of the FDA's Center for Devices and Radiological Health. "Today's action can provide an important public health tool that offers individuals more information about their health, including possible predisposition for certain cancers, which can help guide physicians to provide appropriate monitoring and potential therapy, based on discovered variants."
According to the Centers for Disease Control and Prevention, there are more than 100 different documented types of cancer, a disease in which abnormal cells divide out of control and are able to invade other tissue. It is the second leading cause of death in the United States behind heart disease.
The Invitae Common Hereditary Cancers Panel can be used as a tool to help identify inherited causes of various types of cancers. Patients should speak with a healthcare professional, such as a genetic counselor, to discuss any personal/family history of cancer, as such information can be helpful in interpreting test results. Importantly, this test is not intended to identify or evaluate all known genes that can provide insight into predisposition for cancer.
Over the next two weeks, the FDA is due to release its verdicts on Alnylam’s Onpattro in cardiomyopathy of ATTR and Bristol Myers Squibb’s Opdivo in adjuvant melanoma. But first, the regulator will convene an advisory committee meeting to debate the merits of Amgen’s Lumakras in non-small cell lung cancer.
AdComm to Weigh Full Approval of Amgen’s Lumakras in NSCLC
On October 5, the FDA’s Oncologic Drugs Advisory Committee will meet to discuss Amgen’s supplemental New Drug Application (sNDA) seeking full approval of Lumakras (sotorasib) in non-small cell lung cancer (NSCLC).
Lumakras, an oral inhibitor of G12C-mutated KRAS, won the FDA’s accelerated approval for NSCLC in May 2021. The drug is indicated for patients with KRAS G12C-mutated locally advanced or metastatic disease as determined by an FDA-approved test, and for those who have undergone at least one prior line of systemic therapy.
Amgen has since generated more data to back Lumakras and support its bid for traditional approval. In September 2022, the company posted findings from the Phase III CodeBreaK 200 study showing that the KRAS inhibitor achieved a significantly better progression-free survival and overall response rate than docetaxel.
Meanwhile, overall survival (OS), a key secondary endpoint, was not significantly different between the Lumakras and docetaxel arms. CodeBreaK 200 was not powered to detect a statistical difference in OS, a spokesperson told BioSpace at the time.
The FDA’s panel of external experts will discuss findings from CodeBreaK 200 and determine whether Lumakras’ benefit/risk ratio supports full approval. The FDA’s verdict is due on or before December 24.
Amgen is also developing Lumakras in other solid tumor types, including colorectal cancer and small cell lung cancer.
Alnylam Seeks Onpattro’s Expansion to Cardiomyopathy of ATTR
The FDA will render a decision by October 8 regarding an sNDA submitted by Alnylam seeking to add a second indication for its siRNA therapeutic Onpattro (patisiran).
Alnylam won its first approval for Onpattro in August 2018 in polyneuropathy of hereditary transthyretin-mediated (hATTR) amyloidosis. ATTR amyloidosis is a rare and progressive disease characterized by the build-up of misfolded transthyretin in various organs, including the nerves, that lead to their dysfunction. These proteins can also accumulate in the heart, stiffening its walls and compromising its pumping function.
Alnylam’s sNDA, which the FDA accepted in February 2023, proposes patisiran as a treatment for ATTR amyloidosis with cardiomyopathy. The application includes data from the Phase III APOLLO-B trial, which demonstrated that patisiran improved quality of life and functional capacity in patients with ATTR-cardiomyopathy.
The study also found patisiran to be safe, with most side effects being mild or moderate in severity. Adverse events were consistent with what had been established in previous studies.
In September 2023, the FDA’s Cardiovascular and Renal Drugs Advisory Committee voted 9–3 in favor of Alnylam, finding that the company’s data show a favorable benefit-risk profile for patisiran in this indication. The regulator is not bound by the advisory committee’s findings, though it often follows its advice.
Onpattro, an injectable double-stranded siRNA therapeutic, works by binding to the mRNA molecule that encodes transthyretin. This tags the mRNA for destruction, resulting in overall lower levels of the protein.
BMS Bids to Bring Opdivo to an Earlier Melanoma Setting
On or before October 13, the FDA will release its decision regarding Bristol Myers Squibb’s supplemental Biologics License Application (sBLA) proposing Opdivo (nivolumab) as an adjuvant monotherapy in patients with completely resected stage IIB or IIC melanoma.
Opdivo is already indicated for melanoma, for which it earned its first approval in December 2014. With the sBLA currently under review, BMS seeks to push into an earlier indication.
“Patients with stage IIB or IIC melanoma tend to be at high risk of disease recurrence,” Gina Fusaro, vice president and development program lead at BMS, said in a statement alongside the FDA’s acceptance of the sBLA. “Approximately one-third of stage IIB and half of stage IIC patients experience recurrence within five years after surgery.”
BMS is backing its application with data from the Phase III CheckMate -76K trial, which showed Opdivo reduced the risk of recurrence or death compared to placebo by 58% in patients with stage IIB or IIC disease. Recurrence-free survival over 12 months was also higher among Opdivo-treated patients.
As for safety, CheckMate -76K did not detect new signals of concern and Opdivo’s adverse event profile was consistent with that in previous studies.
Opdivo is approved for several other cancers, including NSCLC, head and neck squamous cell carcinoma, esophageal cancer, hepatocellular carcinoma and renal cell carcinoma. BMS is continuing to study the therapeutic potential of Opdivo, alone or in combination with other treatments, in earlier disease stages.
The research landscape for neurodegenerative diseases has undergone a monumental shift in the past year with the FDA approval of Eisai and Biogen’s Leqembi in Alzheimer’s disease and a regulatory decision for Eli Lilly’s donanemab expected by the end of 2023. While Alzheimer’s patients and researchers celebrate this momentum, another group is also heartened: researchers studying Parkinson’s disease.
Both Alzheimer’s and Parkinson’s are progressive diseases that affect proteins in the brain, though it’s traditionally thought that the similarities end there. But experts told BioSpace that the rising tide in Alzheimer’s research has the potential to accelerate the study and treatment of Parkinson’s disease by drilling down into biological mechanisms of neurodegeneration, mainstreaming the use of biomarker data and uncovering potential shared mechanisms. These advances, they say, could inform clinical trial design and analysis in Parkinson’s and usher in a funding environment that could spell progress for a notoriously intractable condition.
“There’s a lot of optimism now in the field that this is a breakthrough in neurodegeneration itself, not just in Alzheimer’s disease,” said Joanne Taylor, senior vice president of research at Gain Therapeutics.
Biological Cascades
Parkinson’s disease is characterized by a loss of dopamine-producing neurons in a region of the brain called the substantia nigra. Most people with Parkinson’s also have deposits of abnormal alpha-synuclein protein, which forms into clumps called Lewy bodies inside the neurons. These irregular deposits cause many of the motor and cognitive symptoms associated with the disease. Tracking disease progression quantitatively over time, however, is still an open area for research, said Akihiko Koyama, a leader at The Eisai Center for Genetics Guided Dementia Discovery.
Recently—beginning with Alzheimer’s—scientists have made progress toward a biological understanding of neurodegeneration, Koyama told BioSpace. “One big change happening . . . is that we are defining the disease biologically when before we were defining it symptomatically,” he said. This means that instead of relying exclusively on one readout, researchers can study multiple biomarkers, including amyloid beta protein, tau protein and neuroimaging results from MRI scans in the case of Alzheimer’s.
Gene Kinney
In Parkinson’s disease, one biomarker of interest is alpha-synuclein protein, Gene Kinney, CEO of Prothena, told BioSpace. This “likely plays a very important role” in the development of the disease, even before a person might present with clinical symptoms, Kinney said.
In collaboration with Roche, Prothena is testing an investigational Parkinson’s treatment, prasinezumab, that targets alpha-synuclein to stop it from spreading between neurons. Roche has fully enrolled participants for a Phase IIb study, Kinney said, with top-line data expected in 2024.
The shift from symptom- to biology-based definitions via the use of biomarkers is not exclusive to Alzheimer's and Parkinson’s. Biogen’s Qalsody (formerly tofersen) for SOD1-ALS won FDA accelerated approval in April based largely on data showing a reduction in the biomarker neurofilament light chain (NfL)—this after the drug failed to meet the clinical endpoint in Phase III. Now, Taylor said, companies with investigational Parkinson’s drugs are looking to apply these same insights.
“The availability of biomarkers is becoming very important because these diseases really start happening a long time before symptoms start to appear,” she said. Incorporating biomarker readouts into clinical trials for Parkinson’s is appealing for several reasons. One, Taylor said, is that it allows enrollment earlier in the disease process since people who develop motor and neurologic symptoms of Parkinson’s may already have had changes occurring in their brains years before the onset of these symptoms. Preventing the disease cascade may prove to be more attainable than reversing changes decades in the making, Taylor noted.
Second, she said that collecting multiple biomarkers for trial participants increases the odds that researchers can identify a significant signal that a drug is working, which can also shed light on how it works.
Finally, biomarkers can act as preliminary signals as to whether to continue a long and costly trial for a Parkinson’s drug candidate. Such encouraging preliminary signs aren’t just a boon for researchers—this feedback can also encourage investors, Taylor said. “If we can show an effect on biomarkers, it’s a reason to believe that this drug will work on the disease. We think that investors will be very excited about that.”
Shared Mechanisms
The key protein biomarkers in Alzheimer’s and Parkinson’s—amyloid beta and alpha-synuclein, respectively—likely share an important characteristic. Both are pathological, Kinney said, meaning they are each thought to drive disease progression as opposed to indicating the disease process.
While they are distinct proteins that may affect neurons in their own ways, Koyama said further research into the causes of Alzheimer’s might clarify a shared mechanism for how incorrectly folded, disease-causing forms arise and spread. While the target of the protein might be different, “There could be a very similar mechanism happening.”
The reciprocal benefits of neurodegenerative research go the other way too. Gain’s disease-modifying compounds for Parkinson’s, belonging to the class of small-molecule structurally targeted allosteric regulators (STARs), have also shown early signs of acting on Alzheimer’s, Taylor said. Because the compounds improve lysosomal health, they may act upstream of the changes that occur in both diseases. In cellular models of Alzheimer’s, Gain’s compounds prevented amyloid beta toxicity as well as tau hyperphosphorylation.
“It could be that, just by improving the lysosomal health, we could have an effect on pretty much all of these diseases where protein misfolding is involved,” Taylor said.
A Boon for Collaborations
Success in Alzheimer’s clinical trials is a proof point not only for the basic science but also for the research collaborations behind it, Kinney said.
Massive studies under the umbrella of the Alzheimer’s Disease Neuroimaging Initiative (ADNI) bridge academia, industry and government research institutions. The Parkinson’s Progression Markers Initiative (PPMI), led by the Michael J. Fox Foundation, aims to achieve the same level of collaboration. In 2021, the consortium announced plans to triple enrollment numbers in its longitudinal clinical study. One of the initiative’s goals is to identify biomarkers across each stage of Parkinson’s—work that Kinney said will undoubtedly help drug developers.
A final cross-therapeutic lesson, Kinney said, is that the moonshot for Parkinson’s should be a combination of effective drugs rather than any single magic bullet. The approval of a landmark Alzheimer’s therapy has sparked renewed investor interest in Parkinson’s research, with the hope that bets on multiple drugs will eventually pay off.
“When we think about medicine, that first breakthrough is a signal of good things to come,” Kinney said. “What we're seeing today is the tip of the iceberg with respect to where this field can go.”
