safety Archives - First Washington News

November 10, 2022

Experimental vaccine passes phase 1 safety trials

A woman poses sideways baring her shoulder and part of her breast — Experts are working on creating vaccines for different types of cancer, including breast cancer. Alina Hvostikova/Stocksy

Breast cancer is currently the most frequently diagnosed cancer in the United States, and globally it is the world’s most prevalent cancer.
According to new phase 1 clinical trial data, a new plasmid DNA-based vaccine that is able to target a receptor in breast cancer appears safe.
The non-randomized study showed an increased immune response after vaccination in people with advanced-stage ERBB2-positive breast cancer.

According to the World Health Organization, 2.3 million women were diagnosed with breast cancer in 2020, and there were over 7.8 million women alive who had been diagnosed with breast cancer in the previous 5 years.

Being female is the biggest risk factor for breast cancer, but around 1{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809} of breast cancers do occur in men. The treatment of breast cancer follows the same principles for both sexes.

Speaking to Medical News Today Dr. Kotryna Temcinaite, senior research communications manager at Breast Cancer Now explained:

“Breast cancer is not a single disease, which makes it more difficult to treat. There are many types of breast cancer and treatments that work well for some people, may not work as well for others. That’s why we need to undertake further research into the disease, develop [k]inder and smarter treatments.”

Now, new research led by Dr. Mary (Nora) L. Disis, at the University of Washington Medicine Cancer Vaccine Institute on an experimental vaccine against breast cancer has shown it generates a strong immune response to ERBB2—formerly called HER2—a key tumor protein.

The study is published in the journal JAMA Oncology

The completed study was a single-arm phase 1 clinical trial that followed 66 people ages 34 – 77 years who had advanced-stage ERBB2-positive breast cancer. Researchers analyzed the data twice—from January 2012 to March 2013 and from July 2021 to August 2022.

Participants were vaccinated with either 10ug, 100ug, or 500ug doses of the plasmid DNA vaccine every month for three months. The researchers measured blood immunity and vaccine toxicity at set time points and assessed the DNA persistence of the vaccine via biopsy samples taken from the vaccine site at 16 and 36 weeks.

The researchers noted the most common side effects associated with the injection, 33{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809} recorded flu-like symptoms, and 36{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809} fatigue.

Participants who received the higher vaccine doses of 100 μg and 500 μg demonstrated a stronger immune response than those who received the 10ug dose, but there was no significant difference between the immune responses to the 100ug and 500ug doses.

The research team also found DNA persistence at the injection site was greatest with the highest vaccine dose and that this DNA persistence was associated with more rapidly waning immunity.

The study’s lead author Dr. Disis explained that the problem with current breast cancer treatments is “disease recurrence after optimal treatment.” She said the disease recurred because a small amount of cancer remained undetected.

“Vaccines will stimulate T-cells which can be programmed to hunt down these last remaining cells in the body and kill them. Stimulating effective immunity is the only way I know we can sterilize the body from all breast cancer cells.”
— Dr. Mary (Nora) L. Disis

“Ideally, it would be great to prevent all cancers before treatment is needed. We have already made way with some vaccines in cancer prevention such as the hepatitis B vaccines against hepatocellular carcinoma and HPV against cervical cancer,” said Dr. Bhavana Pathak, board certified hematologist and medical oncologist at MemorialCare Cancer Institute at Orange Coast Medical Center, California, who was not involved in the study.

Exciting potential

Dr. Temcinaite believes a vaccine has “exciting potential” for treating breast cancer. However, she said that “Scientists must investigate what to include in a vaccine, to trigger the right immune response.”

Breast Cancer Now is currently funding research to design a new cancer vaccine, specifically targeting the protein p53.

Dr. Parvin Peddi, medical oncologist and director of Breast Medical Oncology at Providence Saint John’s Health Center and associate professor of medical oncology at Saint John’s Cancer Institute, California further explained to MNT:

“[T]his is the first study in my knowledge to examine a HER2 specific vaccine for patients with HER2 positive metastatic breast cancer who are in remission. Although it’s an early study and it was not compared directly to patients not receiving the vaccine, the survival of patients seen in this study is much more than expected with observation.”

Dr. Disis said she believes there is a “good chance” breast cancer vaccines will be in use in clinics in about 5 years.

“Clinical trials of breast cancer vaccines given alone or with other treatments have increased by about 25{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809} in the last several years. There are many groups working on ‘next-gen’ vaccines with very effective delivery technologies and adjuvants,” she told MNT.

Dr. Pathak echoed similar thoughts. She called the current study a “building block showing an increase[d] immune response against specific targets for patients with cancer.”

“Once later phase trials are completed showing efficacy in addition to tolerability, we can potentially anticipate seeing vaccines in clinic,” she said.

But could similar vaccines be developed to treat other types of cancer? Dr. Disis said she believes that is where cancer treatment’s future is headed.

“[Yes.] At the UW Medicine Cancer Vaccine Institute we have programs in breast cancer, ovarian cancer, colon cancer, prostate cancer, and bladder cancer vaccines and ideas for others,” she elaborated.

However, experts have also expressed caution about the trial’s early results.

Dr. Temcinaite said it was “too early to tell whether treatment vaccines for cancer could replace other existing treatments.”

“If [vaccines] are proven to be successful, at first they are most likely to be used alongside existing treatments, until we have enough data to understand who can safely skip any particular step in breast cancer treatment.”
— Dr. Kotryna Temcinaite

Dr. Pathak also raised caution that this study has only been completed in people with breast cancer. “[M]ore studies will be needed to address the possibility of primary prevention,” she pointed out.

“In general, if the protein that is targeted by the vaccine is also found in [healthy] cells, it would be important to watch for autoimmune side effects. For example, heart muscle also has HER2 expression. Although no excess cardiac side effects were reported in this study, it would be important to watch that in larger studies,” Dr. Peddi added.

It is also important to understand how long the benefits of these vaccines may last. The immune response wanes after vaccination so, it would be interesting to understand if booster vaccines might be needed for some patients.

When asked about the next steps Dr. Disis told MNT that the remarkable results they got from the Phase I trial for the HER2 vaccine lays the ground for future studies.

“The next step is to formally test that observation. In the Phase II study, we will randomize HER2-low patients to receive the vaccine or an immune-stimulating agent. The endpoint will be whether we do prevent disease recurrence,” she said.

Dr. Temcinaite advised that these new vaccines might not work for everyone who receives a breast cancer diagnosis.

“[M]ore research to discover new ways to treat breast cancer and build our understanding of who will and who won’t benefit from particular treatments and why,” she said.

October 25, 2021

Biden to nominate No. 2 U.S. auto safety official to head NHTSA

WASHINGTON — President Joe Biden on Monday announced strategies to nominate the No. 2 car safety formal and a former California Air Assets board formal to head the Nationwide Freeway Site visitors Safety Administration.

Steven Cliff, who has been deputy administrator because February, has been a critical figure in the Biden administration’s proposed rewrite of gas economic system criteria by way of 2026 and is overseeing the department’s ongoing safety probe of Tesla Inc. and investigation of regardless of whether 30 million motor vehicles developed by approximately two dozen automakers have unsafe air luggage.

The White Dwelling also options to announce Duke University engineering and laptop science professor Missy Cummings as the new senior adviser for basic safety at NHTSA.

NHTSA, which is element of the U.S. Transportation Department, faces a backlog of pending vehicle basic safety polices and has not had a Senate-verified administrator considering that January 2017. There has not even been a nominee for NHTSA’s leading career due to the fact 2019.

NHTSA in August proposed substantially revising the Trump administration’s rollback of Company Ordinary Fuel Overall economy policies, proposing raising gasoline effectiveness by 8 {cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809} each year for the 2024-2026 model many years.

Cliff said the proposal lessens “local climate pollution by roughly the similar quantity as if we took far more than 5 million of today’s cars off the highway.”

Given that the COVID-19 pandemic, the U.S. has witnessed a sustained raise in website traffic fatalities that NHTSA has ascribed to impaired driving, rushing, a failure to dress in seatbelts and other unsafe habits.

NHTSA previous month estimated 8,730 people died in motor vehicle crashes in the initial 3 months of 2021, when compared with 7,900 fatalities during the exact period very last calendar year — up 10.5 percent in spite of a 2.1 p.c drop in miles driven.

Last thirty day period, NHTSA questioned Tesla why it has not issued a recall to address program updates made to its Autopilot driver-aid system.

NHTSA in August opened a official protection probe into Tesla’s Autopilot program in 765,000 U.S. automobiles immediately after a sequence of crashes involving Tesla styles and emergency vehicles.

NHTSA in June issued an order demanding automakers and operators of vehicles equipped with state-of-the-art driver aid or automatic driving devices to immediately report crashes.

Cummings in a 2018 interview said the U.S. needs “an solely new regulatory framework exactly where an company like NHTSA would oversee” autonomous automobiles, adding the company “does have the authority to mandate tests and other interventions, but they are not carrying out it.”

October 22, 2021

Primatene Mist: Product reviews and safety

We consist of goods we feel are practical for our readers. If you purchase by inbound links on this page, we may perhaps make a little fee. Here’s our procedure.

Amphastar Prescribed drugs can make the Primatene Mist inhaler, a nonprescription medicine suitable for men and women with delicate bronchial asthma. It is out there from various pharmacies, on the web and in particular person.

Though no prescription is needed, it is important to think about opportunity interactions and other warnings before attempting this treatment.

Under, we provide detailed information about this inhaler, like where to purchase it. We also explain the warnings and when to get hold of a health practitioner.

The active ingredient in this inhaler is epinephrine, a bronchodilator. These prescription drugs relax the smooth muscle tissues in the airways, and this can reduce indicators of asthma, these as wheezing and upper body tightness.

Master more about the various forms of bronchial asthma inhalers.

In 2011, Primatene taken out Primatene Mist from the current market. At the time, this solution contained chlorofluorocarbons (CFCs), which can deplete the ozone layer.

Instead of CFCs, Primatene Mist now contains hydrofluoroalkane (HFA 134a), a propellant that is accepted below global and United States law.

A 2021 study observed that the new Primatene Mist inhalers that contained HFA 134a are as safe and sound and efficient as the outdated kinds that contained CFCs.

Amphastar Prescription drugs is a organization that manufactures injectable, intranasal, and inhalable products and solutions, these types of as Primatene Mist.

Amphastar Prescription drugs and Primatene do not have Much better Company Bureau or Trustpilot internet pages. The inhaler’s Amazon web site demonstrates an ordinary buyer ranking of 4.6 out of 5 stars.

Optimistic critiques mention performance, and a number of shoppers appreciated how a lot a lot easier it was to invest in this item than to wait around for their prescription medicine.

However, people today who still left negative opinions described a burning sensation in their lungs soon after using the product, and a single human being reported shaking.

Primatene notes that the Primatene Mist inhaler is only appropriate for folks who are 12 many years of age or more mature.

A particular person need to only use this inhaler if a health care qualified, these as a health care provider or a pharmacist, has recommended it. It is also critical to be aware that this products is not a substitute for a prescription treatment.

It is also vital to think about other warnings prior to paying for this inhaler.

Primatene Mist is only suited for folks who have received a diagnosis of asthma from a medical doctor.

Primatene adds that persons should check with a health practitioner in advance of working with Primatene Mist if they have ever wanted hospitalization for asthma, or if they have:

Primatene Mist can boost a person’s coronary heart amount and blood pressure. This can boost the hazard of stroke, specially in men and women who:

have a heritage of a rapid heart charge and significant blood strain
use the inhaler more frequently than the business recommends
use a larger dosage than the organization endorses

In addition, people should really steer clear of foods and drinks that comprise caffeine and nutritional supplements that incorporate something that acts as a stimulant when making use of this item.

Primatene warns that people today should really stop utilizing their Primatene Mist inhaler and speak to a medical doctor if they working experience any of the subsequent:

worsening bronchial asthma symptoms
issues sleeping
a fast heart price
nervousness
tremors
a seizure

Primatene experiences that folks who choose prescription monoamine oxidase inhibitors (MAOIs) need to not use Primatene Mist. This consists of any individual who has taken an MAOI in the past 2 months. Anybody doubtful about this steerage ought to seek advice from a healthcare skilled.

In addition, men and women should really discuss with a pharmacist or a physician initially if they are having:

prescription medications for bronchial asthma, being overweight, or depression
any prescription or nonprescription medicines that consist of phenylephrine, pseudoephedrine, ephedrine, or caffeine

The maker does not offer Primatene Mist on its site. Men and women can buy it at numerous pharmacies and other outlets, which includes:

These selling prices had been appropriate at the time of publishing.

The American Lung Affiliation lists the subsequent treatments that medical doctors may perhaps prescribe for asthma:

Anti-inflammatory remedies: Medical practitioners may refer to these medicines as corticosteroids or steroids. They decrease inflammation and mucus output in the airways to make breathing easier. A particular person might have to have to rinse out their mouth with h2o right after using these prescription drugs to lower the danger of a yeast infection producing in their throat.
Anticholinergics: This treatment comes in a metered-dose inhaler and relaxes the muscle groups in the airways. Physicians may well recommend these in mix with inhaled corticosteroids.
Antibiotics: Health professionals could prescribe antibiotics if bronchial asthma flare-ups arise with an an infection.

Find out more about asthma treatment.

Individuals ought to only use about-the-counter bronchial asthma remedies if a health care provider or pharmacist endorses it.

Master extra about around-the-counter asthma medicines.

Any individual who suspects that they have asthma must consult a healthcare skilled. Indications of asthma involve:

Bronchial asthma indicators can worsen, in what is identified as an “attack.” A person may perhaps be experiencing an asthma attack if, for example:

Using an inhaler does not relieve the indicators.
They are getting it challenging to breathe.
They are acquiring it hard to communicate, try to eat, or slumber due to the symptoms.

Any person who may possibly be owning an asthma attack need to sit upright and test to breathe slowly but surely. If the person does not have an emergency, or reliever, bronchial asthma inhaler, they need to contact 911 or their regional crisis amount and question for an ambulance.

The National Wellbeing Support states that, if the person has a reliever inhaler, they ought to acquire a single puff every single 30 or 60 seconds, up to a optimum of 10 puffs. If this does not function or makes the man or woman experience even worse, they need to get urgent medical consideration.

The underneath are some of the most frequently questioned issues about Primatene Mist:

Is Primatene Mist secure for asthma therapy?

The Food and drug administration has authorized Primatene Mist for the procedure of mild bronchial asthma.

This inhaler is only ideal for people with a analysis of asthma. A person need to only use it if a medical doctor or pharmacist has encouraged it.

In addition, Primatene Mist is not acceptable for youngsters under 12 several years of age.

What are the substances?

The active component is epinephrine, which is a bronchodilator. It relaxes the muscular tissues in the airways.

Primatene Mist also has many inactive components:

dehydrated liquor (1{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809})
HFA 134a
polysorbate 80
thymol

Was Primatene Mist discontinued?

Primatene Mist’s authentic formulation contained CFCs, a propellant that depletes the ozone layer. The company stopped issuing this inhaler in 2011.

Now, Primatene Mist has a various formulation. As an alternative of CFCs, it consists of HFA 134a, a propellant permitted below U.S. and worldwide law. This new version is accessible at pharmacies on the internet and in man or woman.

Primatene Mist is an inhaler that can minimize indicators of moderate bronchial asthma. It is out there devoid of a prescription.

Prior to purchasing the product or service, examine its suitability with a health practitioner or pharmacist. The inhaler can trigger facet effects, and is not acceptable for people who have selected wellness circumstances or who are using specific other remedies.

October 16, 2021

What we know about molnupiravir: Data and safety concerns

In the search for effective COVID-19 treatments, many drugs have failed to live up to their early promise. In a recent trial, seen as an important advance, the oral antiviral drug molnupiravir halved the risk of hospital admissions and deaths from COVID-19. Medical News Today explored the evidence to see whether this optimism is justified.

The experimental drug molnupiravir has brought fresh hope in the fight against COVID-19. But what do we know about it so far? Image credit: Jordan Lye/Getty Images

A global trial, led by the pharmaceutical company Merck — known as MSD outside the United States and Canada — and Ridgeback Therapeutics, has found that the companies’ experimental antiviral drug molnupiravir reduces the risk of hospital admission or death from COVID-19 by approximately 50{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809}.

Although this was a small-scale trial, these positive results have led to countries rushing to sign up for supplies of the drug.

In the randomized, phase 3 trial, scientists gave molnupiravir or a placebo to 775 people. All the participants had tested positive for SARS-CoV-2 infections and experienced mild to moderate COVID-19 symptoms that had begun no more than 5 days earlier.

Stay informed with live updates on the current COVID-19 outbreak and visit our coronavirus hub for more advice on prevention and treatment.

Every participant had at least one risk factor for severe COVID-19 but had not been admitted to a hospital. Risk factors included obesity, an age of over 60 years, diabetes, and heart disease.

The scientists allocated each of the 775 participants randomly to one of two groups. One group received molnupiravir and the other a placebo. The participants took the capsules twice a day for 5 days.

Of the 385 patients taking molnupiravir, 28 were admitted to a hospital, compared with 53 of those in the placebo group. Eight of the placebo group participants died, while all those receiving the antiviral were alive at the end of the 29-day study period.

Recruitment into the study has now been halted because of these overwhelmingly positive results. The manufacturer, Merck, is applying for emergency use authorization from the Food and Drug Administration (FDA).

The Singapore health ministry has signed a purchase agreement for molnupiravir, and the European Medicines Agency is considering a rolling review of the drug.

“With these compelling results, we are optimistic that molnupiravir can become an important medicine as part of the global effort to fight the pandemic.”

– Robert M. Davis, chief executive officer and president of Merck

Merck plans to produce 10 million courses of the treatment in 2021 and more in 2022.

The study results have been greeted with optimism. Prof. Tim Spector, a professor of genetic epidemiology at King’s College London, told MNT: “This is an exciting result from a randomized study of 775 patients, showing major effects in reducing severity and death from a simple pill given at the onset of infection.”

Molnupiravir belongs to a class of antivirals called mutagenic ribonucleosides. These change the viral genetic material and introduce errors to prevent replication and transcription of the viral genome.

Inside the host cell, molnupiravir is converted to molnupiravir triphosphate. When the virus tries to replicate, molnupiravir triphosphate is incorporated into the viral RNA instead of the nucleoside cytidine, causing a mutation.

The mutation stops the virus from replicating. This keeps numbers of the virus in the body low and should reduce the severity of the disease.

Other drugs that interfere with viral RNA have shown potential as COVID-19 treatments. Remdesivir, an intravenously administered drug that interferes with an enzyme essential for replicating viral RNA, showed early promise.

Although the FDA has granted approval to remdesivir, the World Health Organization (WHO) no longer recommends it as a COVID-19 treatment, due to insufficient evidence to support its use.

The advantage of molnupiravir is that, unlike all the other potential treatments so far, it is an oral tablet that a person can take outside a clinical setting. At a projected cost of around $700 per person for a 5-day course, it is also more affordable than other drugs. However, this cost is still likely to limit its use.

“Antiviral treatments that can be taken at home to keep people with COVID-19 out of the hospital are critically needed. We are very encouraged by the results from the interim analysis and hope molnupiravir, if authorized for use, can make a profound impact in controlling the pandemic.”

– Wendy Holman, chief executive officer of Ridgeback Biotherapeutics

Prof. Sir Peter Horby, a professor of emerging infectious diseases and global health at the University of Oxford, is largely optimistic: “A safe, affordable, and effective antiviral would be a huge advance in the fight against COVID.”

However, he retained a note of caution: “It is important to remember that the absolute risks were 14{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809} reduced to 7{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809}, so quite a lot of people need to be treated to prevent one hospitalization or death. This means the drug needs to be very safe and affordable.”

This caution was echoed by Prof. William Schaffner, a professor of infectious diseases at the Vanderbilt University School of Medicine, who said: “In the studies in very high risk patients, it reduced the level of serious disease by only half. It’s not a magic pill.”

He added: “In research settings, you can ensure that people take the pill as directed. In practice, there is usually a lower success rate than in clinical trials.”

Dr. Peter English, a retired consultant in communicable disease and a past chair of the British Medical Association Public Health Medicine Committee, has also expressed doubts: “The problem for antivirals like Merck’s molnupiravir is that they would have to be used before people are (usually) deemed ill enough to need anything other than symptomatic self-care treatment.”

“Unless an antiviral medication could be made so cheap and so safe that it can be used ‘on spec’ by people who might have COVID-19, [it is] unlikely to be widely useful,” he adds.

Despite widespread optimism following the study results, some experts have raised concerns about the safety of a drug that works by causing mutations.

As molnupiravir causes viral RNA to mutate, there are concerns that it might cause mutations in host cells, as well. One study in animal cell cultures found mutations in cells treated with molnupiravir.

This has led to worries that the drug might cause cancers or birth abnormalities. The authors of the animal cell study recommend that this mutagenic potential be assessed in vivo, focusing on rapidly dividing cells. Additionally, they recommend monitoring to assess potential genotoxic side effects.

“It’s worth noting that people involved in the trial were instructed to abstain from heterosexual sex or use contraception. While this is routine practice with some other medicines, such as cancer chemotherapy, it suggests that the drug has the potential to cause birth defects should someone become pregnant.”

– Dr. Simon Clarke, associate professor of cellular microbiology at the University of Reading

Prof. Schaffner was less concerned about the possible genetic implications: “The FDA would certainly not have permitted clinical trials in humans if they thought there were any reasonable danger. […] Animal studies showed no adverse effects.”

In this trial, molnupiravir was effective against all variants, including the Delta variant, which was shown in a recent study to have a 235{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809} increased risk of intensive care unit admission, compared with the original variant.

These positive results applied to people who had received molnupiravir soon after the onset of mild to moderate symptoms. A previous trial showed no benefit in giving the drug to patients already in hospital with COVID-19.

As an early treatment, molnupiravir could, Prof. Schaffner agrees, “offer another opportunity to prevent serious disease.”

“Although [this trial] had relatively small numbers analysed (fewer than 400 per group), it had much better results than the study done in hospitalized patients. It approximately halved the rate of hospitalization and notably reduced the number of deaths. Preventing the virus from replicating at an early stage seems very beneficial.”

– Prof. Stephen Evans, professor of pharmacoepidemiology at the London School of Hygiene & Tropical Medicine

So, is molnupiravir the drug we have been waiting for to bring COVID-19 under control? Perhaps, but the evidence is not yet conclusive.

Prof. Spector is among those keen to see more trial results. “We are told there were few side effects, but it would be good to know more details and see a full peer-reviewed publication,” he said. “But if this pans out, it will be a major game-changer for [COVID-19] treatment and possibly other viruses.”

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