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Friday, June 10, 2022

What Terrorists Learned from Covid

 A

merican counterterrorism experts’ biggest fear remains a biological weapons attack in the United States. A conventional bomb can kill hundreds or even thousands, but a biological weapon can surreptitiously invade, spread, mutate, and kill millions. Biological weapons have been used throughout history, from poisoning wells to “gifting” smallpox-infected blankets. Whether you believe that Covid-19 came from bats sold in a wet market or escaped from a Chinese lab, terrorists are observing the pandemic’s toll on America and taking notes for a future biological attack. What lessons might they have learned from America’s reaction to Covid?

The first is that America is unprepared for a biological attack. Our national defense experts tend to look backward to past threats rather than preparing for future ones. The U.S. botched the response to swine flu under the Obama administration, avoiding a damaging experience only through some good luck, but still failed to engage in research to address future threats. Terrorists can plan on the nation not having a ready-made response to any tailor-made virus.

The next lesson: America does not affirmatively defend itself from biological threats. We train our police to respond to active shooters in schools. We take off our shoes for scanning before we get on planes. But we do not regularly monitor wastewater supplies for the presence of new and dangerous pathogens. Only now are some local governments discovering that they can track Covid outbreaks by testing wastewater. We also leave our water supply wide open to attacks; ten terrorists in ten cities adding a highly infectious virus to the water supply would have a devastating nationwide impact.

The pandemic has revealed that America’s investigative capabilities—scientific and military—are either fragile or fainthearted. Two years in, we still have no definitive answers about the origin of Covid. Nor do we appear to be pressing China particularly hard for an explanation. Tracing biological weapons is difficult unless you act quickly, competently, and decisively.

Terrorists also learned that politics is corrupting our scientific organizations. From federal agencies to private universities, ideology is distorting science. When science is filtered through the lens of politics, nobody is likely to have much respect for empirical fact-finding. Thus, mixed public-health messaging eventually leads sensible people to the conclusion that some scientists refuse to admit their own ignorance.

America’s political polarization has taught terrorists that our divisiveness will prevent any immediate and unified response to a biological attack. Many Democrats expressed doubt about Covid vaccines when Donald Trump was in the White House. When President Biden took office, some Republicans began questioning the vaccines. Some states demand vaccines and masks everywhere; some leave it to individual choice. The politicization of science, egged on by the mainstream media, has reduced public trust.

Covid also taught terrorists that American supply chains for critical materials are weak, fractured, and often reliant on materials from outside the United States. Necessary supplies for vaccines, tests, and medical items come from other countries, forcing the nation to face shortages of items critical to our medical defenses. For instance, the United States struggled with a shortage of Covid testing kits. Over 50 percent of those kits are manufactured in China.

Finally, potential bioterrorists have learned that Americans are physically vulnerable to a biological attack. Our borders are porous. Our population is exceptionally obese and unfit. Particularly in dense urban areas, this lack of physical vitality makes an inviting target for weaponized viruses. The coronavirus took a disproportionately heavy toll on obese Americans. If you’re a terrorist designing a virus, this is hard information to ignore.

Yet some good news remains. The United States retains the ability to innovate quickly: through Operation Warp Speed, American pharmaceutical companies performed a miracle in creating and mass-producing vaccines in an incredibly short time frame. Not since the nation geared up for World War II have we seen such a concerted effort to achieve a singular result. And Americans remain a strong, independent-minded people. Even as the government bungled an economic response to the pandemic, markets rebounded. The American public has awakened to the fact that its leaders and the media might not be fully trustworthy or competent, so the age-old national tradition of questioning authority has returned with vigor.

Last, any terrorist planning a biological attack on the U.S. will have to deal with the reality that Covid has acted as a national stress test. Somewhere in the depths of American law enforcement, agents, prosecutors, and scientists are considering the strategic implications of what we have been through in recent years. They are running models, preparing new approaches and defenses, and learning new lessons. With hard work and luck, they will have solutions in place if and when such a threat emerges.

Cyclerion: Positive Topline Clinical Data for CY6463 in mitochondrial dysfunction

 Data from an eight-patient, open-label study demonstrate improvements across multiple biomarkers of mitochondrial function, inflammation, cerebral blood flow, and functional connectivity

CY6463 was well tolerated, with no reports of serious adverse events (SAEs) or treatment discontinuation due to adverse events (AEs); oral, once-daily administration provided expected CNS exposure

Data support further development of CY6463 in CNS diseases with mitochondrial dysfunction

https://www.biospace.com/article/releases/cyclerion-therapeutics-announces-positive-topline-clinical-data-for-cy6463-in-melas-patients-at-umdf-mitochondrial-medicine-2022-symposium/

Gritstone: Results from Preclinical Study of Self-amplifying mRNA covid vax

 - Results, which were previously pre-printed in bioRxiv, show Gritstone’s second-generation self-amplifying mRNA (samRNA) vaccine candidate drove broad neutralizing antibodies, T cell responses and offered protection against SARS-CoV-2 infection in rhesus macaques --

-- Neutralizing antibody responses were induced at up to a 10-fold lower dose than first-generation mRNA vaccines --

-- Durable protection against SARS-CoV-2 in rhesus macaques observed with the samRNA vaccine regimen supports ongoing therapeutic exploration in coronaviruses and other infectious diseases --

https://www.biospace.com/article/releases/gritstone-announces-results-from-preclinical-study-of-its-self-amplifying-mrna-samrna-vaccine-against-sars-cov-2-published-in-nature-communications/

Valneva Update on European Inactivated, Whole-Virus COVID-19 Vaccine Program

 ValnevaSE (Nasdaq: VALN; Euronext Paris: VLA), a specialty vaccine company, today provides an update on its European inactivated whole-virus COVID-19 vaccine candidate VLA2001.


Following receipt of the European Commission (EC)’s notice of intent to terminate the Advance Purchase Agreement (APA)1, Valneva proposed a remediation plan, which is now subject to further discussion within the EC and among the participating member states.

Some member states have confirmed their interest in having an inactivated, adjuvanted whole-virus vaccine solution in their portfolio. However, the preliminary, unofficial volume indications received from the EC would not be sufficient to ensure the sustainability of Valneva’s COVID-19 vaccine program. This would also impede the future development of the program beyond the current product profile.

If such indications are confirmed, Valneva will not be able to enter into an amendment to the APA that could allow for a reduced order, and the EC is thus likely to terminate the agreement. As a result, Europeans would not have access to Valneva’s inactivated vaccine VLA2001.

Thomas Lingelbach, Chief Executive Officer of Valneva, commented, “We hope that the EC and its member states will continue to evaluate the potential advantages of an inactivated vaccine. There is emerging evidence that hybrid immunity – from a combination of vaccination and natural infection – increases protection against development of severe COVID-19 caused by different variants of concern, and our inactivated vaccine closely mimics natural infection by exposing vaccinees to the entire inactivated SARS-CoV-2 virus. Additionally, market research studies in six European countries indicated material interest in an inactivated COVID-19 vaccine for primary or booster vaccination. We continue to receive messages from people looking for a more traditional vaccine technology and we hope to receive a meaningful order size to further support public health in Europe”.

In parallel, the regulatory process with the European Medicine Agency (EMA) continues as planned. EMA accepted the filing of Marketing Authorization Application on May 19, 20222 and the Committee for Medicinal Products for Human Use (CHMP) is expected to take a final vote during the week of June 21, 2022. Valneva also continues to work with agencies outside of the European Union for potential future approvals and additional purchase agreements.

https://www.biospace.com/article/releases/valneva-provides-update-on-european-inactivated-whole-virus-covid-19-vaccine-program-vla2001/

FDA Requires Disclosure of Suicide Risk for Anti-Baldness Drug

 U.S. health regulators rejected a request to remove popular anti-baldness pill Propecia and its generic versions from the market, but for the first time required patient notification about reports of suicidal behavior in men taking the drug.

The U.S. Food and Drug Administration has previously approved revised Propecia labels that mentioned risks of persistent sexual dysfunction and depression but not suicide. A patient advocacy group, the Post-Finasteride Syndrome Foundation, petitioned the FDA in 2017 to order Merck & Co to either stop selling the drug or require far stronger warnings, citing several scientific studies. Finasteride is the generic name for Propecia.

In a response this week, the FDA said the group's petition "does not provide reasonable evidence" of a causal link between Propecia and persistent sexual problems, depression or suicide. However, based on patient reports, the FDA said it is "requiring the addition of suicidal ideation and behavior" to the adverse reactions listed on Propecia's label.

Merck spinoff Organon on Friday said it "stands behind the safety and efficacy of Propecia," and is working with the FDA "to determine the best path forward." Representatives for the Post-Finasteride Syndrome Foundation could not immediately be reached. The FDA declined to comment.

As early as 2009, Merck knew of more than 200 reports of depression, including suicidal thoughts, in men taking Propecia, according to an internal "risk management" assessment from that year, which was contained in court documents made public following a Reuters request.

In 2011, two years after the Merck risk analysis, FDA analysts disagreed about adding a warning related to suicide, but the regulator ultimately agreed with Merck that the number of suicides was lower than one would expect in that group of patients. Since that decision, the FDA has received more than 700 reports of suicide and suicidal thoughts among people taking versions of the drug.

https://www.usnews.com/news/top-news/articles/2022-06-10/fda-requires-disclosure-of-suicide-risk-for-anti-baldness-drug

Eledon Gains As FDA Grants Orphan Drug Designation

 Eledon Pharmaceuticals 

 received Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) for its drug candidate Tegoprubart for the Prevention of Allograft Rejection in Pancreatic Islet Cell Transplantation.

Tegoprubart is an anti-CD40L antibody with high affinity for CD40 Ligand, a well-validated biological target with broad therapeutic potential.

Tegoprubart is currently investigated in a Phase 2a clinical study for the prevention of allograft rejection in pancreatic islet cell transplantation as part of a CNI-free immunosuppressive regimen.

David-Alexandre C. Gros, MD, Chief Executive Officer, commented : "Tegoprubart has the potential to ameliorate islet cell transplant therapy outcomes by improving graft survival and function while also reducing side effects associated with CNIs. Coming on the heels of positive topline data results from our Phase 2a clinical trial in ALS, this marks another important milestone for tegoprubart as a potentially transformative treatment option."

Tegoprubart previously received orphan drug designation from the FDA for the treatment of amyotrophic lateral sclerosis (ALS).

FDA grants orphan status to support development of medicines for the treatment of rare diseases that affect fewer than 200,000 people in the United States. It also provides benefits of seven-year period of market exclusivity if the drug is approved, tax credits for qualified clinical trials and an exemption from FDA application fees.

https://www.benzinga.com/general/biotech/22/06/27625039/eledon-pharmaceuticals-stock-gains-as-fda-grants-orphan-drug-designation

New Advances Transform Treatment of Prostate Cancer

 The way we treat prostate cancer has changed dramatically in recent years. Advances in MRI imaging have undoubtedly contributed to this change, both in terms of diagnosis — by making targeted biopsies possible — and in terms of our approach to treatment. The emergence of new treatments (next-generation hormone therapy, radionuclide therapy, etc) has also improved the prognosis of patients with metastatic cancer.

For an update on these advances, Medscape interviewed Guillaume Ploussard, MD, a urologist and oncologist at La Croix du Sud Clinic, Toulouse, France, and head of the French Urology Association's (AFU) prostate cancer subcommittee.

Medscape French Edition: The way we treat prostate cancer has changed dramatically in terms of diagnosis and therapeutic approach. In your opinion, what has been the most significant step forward in recent years?

Guillaume Ploussard, MD: The move towards personalized treatment options. Thanks to an improvement in imaging techniques and the contribution made by genomics, we can now better categorize a specific case of cancer, foresee how it will evolve, and adapt our therapeutic approach accordingly for each individual patient.

Our ability to obtain more precise MRI images, along with improvements made in training radiologists to interpret these images, has made us better at detecting prostate cancer. These advances in MRI mean we can identify the most severe cancer cases, which, in turn, stops us from starting treatment in patients who don't need it.

In terms of genetic testing, we are now better at determining an individual's risk and treating patients with greater accuracy. Such testing is used, in particular, to characterize tumors and justify the use of certain treatments, such as poly-ADP ribose polymerase (PARP) inhibitors for metastatic cancers.

Medscape: Oncogenetics has also gathered pace in preventing prostate cancer. How has this affected the treatment you provide?

Ploussard: There has been a growing awareness both in patients and in doctors of the role played by genetics in the risk of developing prostate cancer. It is estimated that less than 5% of cases of prostate cancer are linked to genetic mutations. Nearly 4 years ago, consultation with an oncogenetic specialist was added to the treatment protocol. Patients with a family history of prostate cancer are advised to undergo testing for the following gene mutations: BRCA1, BRCA2, and HOXB13, which are associated with an increased risk of developing an aggressive form of this type of cancer.

For patients over the age of 40 years with mutations, a strategy for the early detection and prevention of prostate cancer has been put in place: prostate-specific antigen (PSA) testing and digital rectal examination, to be repeated on a yearly basis or every 2 years. As a result, overloaded oncogenetic departments are struggling with, but in the process of adapting to, this increase in demand.

Medscape: What about the PSA screening strategy, which has long been maligned for its associated risk of overdiagnosis and overtreatment?

Ploussard: We no longer talk about screening, which implies a systematic and organized evaluation of a patient's risk of cancer, but rather early detection of prostate cancer that is adapted to individual risk. This should be carried out in voluntary, well-informed patients.

The AFU believes that early detection via PSA testing has some benefit in 50- to 75-year-old men with a life expectancy of more than 10 years and men over 45 with an inherited risk. The recommendations have not changed in this regard. In patients with a PSA < 1 ng/mL, testing may be repeated every 3 to 4 years, depending on individual risk profile. This threshold cannot be found in the recommendations but can be taken as a reference point.

Medscape: Imaging has also led to advances in terms of diagnosis and performing biopsies. Why is this change important?

Ploussard: Better prostate MRI imaging means more precise localization of lesions, as well as giving us an estimation of their size and extent, which helps determine a target area for biopsy.

MRI imaging is now recommended as first-line treatment in cases of suspected prostate cancer to identify a possible target area prior to biopsy. Having targeted an area, biopsies are helpful in evaluating a disease and, therefore, in drawing up the most appropriate treatment plan. A spatial distribution of the disease in the prostate is obtained, which limits the functional impact of surgery, for example, without affecting the oncology outcome in any way.

Targeted biopsies are used in addition to systematic biopsies [editor's note: 12 samples from the prostate] to ensure no cancerous lesions are missed. Systematic biopsies allow us to detect 5% to 10% of cancer cases that would go unnoticed with a targeted biopsy.

Medscape: Have these changes in practice also changed how you actively monitor low-risk cancers?

Ploussard: Active monitoring was put in place in response to overdiagnosis of nonsignificant forms of cancer to avoid overtreatment. These advances have clearly reduced overdiagnosis. MRI has also been added to the follow-up pathway for patients requiring active monitoring, to avoid the need for follow-up biopsies when lesions appear stable. It used to be the case that biopsies were carried out every year or 2 years.

In cases where a suspicious area has been picked up by MRI scanning, imaging should be redone each year to evaluate its progress. If no suspicious lesion is detected, imaging can be done every 2 years. Invasive tests are now used much less as part of active monitoring, which is a sign of progress in terms of patient quality of life.

Medscape: In terms of treatments, we have seen the arrival of next-generation hormone therapies for metastatic cancers. What contribution have these new treatments made?

Ploussard: Treatment of the different types of metastatic prostate cancer has changed dramatically in recent years to significantly extend patient life expectancy. The biggest change is the arrival of next-generation hormone therapies (abiraterone, enzalutamideapalutamide, darolutamide, etc) that directly attack cancerous cells in tumors.

These treatments are essentially androgen-receptor inhibitors, which work by stopping tumor cells from performing certain growth-promoting metabolite transformations, while antiandrogens limit the stimulating effect of androgens by reducing their concentration in blood.

For castrate-resistant cases, we also have third-line treatments such as olaparib (Lynparza), an anti-PARP indicated for patients with BRCA1/2 mutations, chemotherapy, or radionuclide therapy to increase life expectancy.

Medscape: Radionuclide therapy is a recent, seemingly promising advance. Can we expect further indications to be added for this targeted treatment?

Ploussard: For the time being, radionuclide therapy has not been approved. Its use is limited to some early access centers. Its approval for treating castrate-resistant metastatic cancer is due to be issued very soon. Other trials are being carried out to assess use of the treatment in earlier phases of the disease.

This radiotherapy has the advantage of targeting cancerous cells using prostate-specific membrane antigen (PSMA) antibodies. The antibodies are associated with a radioactive molecule that is said to kill tumor cells directly. It is therefore well tolerated. The results are very encouraging, and we hope this treatment will be opened up to earlier stages of the disease.

Medscape: Finally, have the changes made to treatment reduced its impact in terms of urinary symptoms and erectile dysfunction?

Ploussard: These side effects are better taken into account, and progress has been made in this area as treatments have evolved. This is largely due to improvements in surgery as a result of the increasing use of robotics in this field and the development of more precise radiotherapy. In terms of surgery, technical improvements have meant that we are now able to preserve the neurovascular bundle surrounding the prostate, which is responsible for maintaining erectile function. Urinary function is also better maintained.

This advance in treatment, facilitated by the improvements seen in MRI scanning, has clearly reduced urinary and erectile dysfunction. Although less common now, these complications must still be borne in mind when treating prostate cancer. That said, if they do occur, we are better placed to treat them.

https://www.medscape.com/viewarticle/975379