Biotech Investors: Mark Your Calendar For May PDUFA Dates

The month of April was a mixed one for regulatory approvals. The Food and Drug Administration delayed approvals for at least three treatment candidates. New molecular entity, or NME, approvals, a measure of innovation in drug research, tapered to merely one for the month.

BioXcel Therapeutics, Inc. 

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 was among the fortunate ones, as the biopharma snagged approval for its Igalmi as a treatment option for agitation associated with neurological disorders.

Bristol-Myers Squibb Company's 

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 heart disease drug mavacamten, which came into its stable following the Myokardia acquisition, cleared the regulatory hurdle. The FDA also gave its nod for the label expansion of Supernus Pharmaceutical, Inc.'s 

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 Qelbree to be used as a treatment option for attention deficit hyperactivity syndrome in adults.

Here are the key PDUFA dates scheduled for May:

Can Phathom Snag Its Maiden Nod?

Company: Phathom Pharmaceuticals, Inc. 

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Type of Application: new drug applications
Candidate: Vonoprazan
Indication: bacterial infection
Date: May 3

Phathom, a clinical-state biopharma, submitted two NDAs to the FDA in September 2021, seeking approvals of two vonoprazan combinations, one with amoxicillin and another with clarithromycin and amoxicillin, as treatment options for Helicobacter pylori infection in adults.

The current standard-of-care therapies, according to the company, now have reduced impact for eradicating the bacterial infection in the U.S. It sees the two combo treatments as offering two new therapeutic options providing superior eradication rates as compared to the standard-of-care of lansoprazole-based triple therapy.

Contingent on the FDA approving the two combinations, the company expects a launch in the U.S. in the second half of 2022.

Pfizer-Myovant Hope For Myfembree Label Expansion Despite FDA Warning Of Deficiency In Application

Company: Pfizer, Inc. 

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 and Myovant Sciences, Inc. 

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Type of Application: supplemental NDA
Candidate: Myfembree
Indication: endometriosis related severe pain
Date: May 6

Myfembree, co-developed and commercialized by Pfizer and Myovant, is being evaluated for the management of moderate-to-severe pain associated with endometriosis. It is a convenient one pill, once-a-day treatment option.

The companies announced last month that the FDA communicated to them certain deficiencies in the NDA that preclude discussion of labeling and/or post-marketing

In May 2021, the FDA approved the treatment for managing heavy menstrual bleeding associated with uterine fibroids in premenopausal women, with a treatment duration of up to 24 months.

Can Third Time Be The Charm For Verrica?

Company: Verrica Pharmaceuticals Inc. 

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Type of Application: NDA
Candidate: VP-102
Indication: viral skin infection
Date: May 24

VP-102, or cantharidin 0.7% topical solution, is being evaluated as a potential treatment option for molluscum contagiosum and common warts. Molluscum, according to Verrica, is a highly contagious viral skin infection affecting approximately six million people, primarily children, in the U.S.

Verrica's original NDA submitted in late 2019 was rejected by the FDA, and following a resubmission by the company, a new PDUFA goal date was announced. The company faced another setback when the drug regulator extended the review period by three months.

Following the extended review, the FDA issued a second complete response letter in September 2021, citing deficiencies at a facility of a contract manufacturer. Verrica's second resubmission was accepted for review in mid-December.

Bristol-Myers Squibb Awaits Approval For Immunotherapy Combo In Esophageal Cancer

Company: Bristol-Myers Squibb
Type of Application: supplemental biologic license application
Candidate: Opdivo and Yervoy
Indication: esophageal squamous cell carcinoma
Date: May 28

The combination of Bristol-Myers Squibb's cancer immunotherapies Opdivo and Yervoy are being evaluated as a first-line treatment for adults with advanced, metastatic esophageal squamous cell carcinoma.

According to statistics quoted by the company, about 19,000 people were diagnosed with esophageal cancer in the U.S. in 2020 and 15,000 died. The Opdivo-Yervoy combo will likely improve upon outcomes with the current standard-of-care, the company said.

Can Amicus Take Its Rare Genetic Disease Treatment Past The Finish Line?

Company: Amicus Therapeutics, Inc. 

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Type of Application: NDA
Candidate: miglustat for AT-GAA
Indication: Pompe disease
Date: May 29

AT-GAA is an investigational two-component therapy that consists of cipaglucosidase alfa, administered in conjunction with miglustat. It is being evaluated for an inherited lysosomal disorder. The disease can be debilitating and is characterized by severe muscle weakness that worsens over time.

Pompe disease ranges from a rapidly fatal infantile form with significant impacts on heart function to a more slowly progressive, late-onset form primarily affecting skeletal muscle. It is estimated that Pompe disease affects approximately 5,000 to 10,000 people worldwide.

Eton Hopes to Earn Milestone Payment From Epilepsy Drug Approval

Company: Azurity Pharma
Type of Application: NDA
Candidate: ET-105 (lamotrigine for oral suspension)
Indication: epilepsy
Date: May

Azurity Pharma acquired lamotrigine from Eton Pharmaceuticals, Inc. 

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 in February 2021, and it has submitted to the FDA results of the product's human factor study in the fourth quarter of 2021. Following this, the agency assigned a PDUFA goal date of May. Eton stands to receive $5 million in milestone payment from Azurity upon the approval and launch of lamotrigine.

https://www.benzinga.com/general/biotech/22/04/26918512/attention-biotech-investors-mark-your-calendar-for-may-pdufa-dates

Chinese Omicron-specific mRNA Covid vaccine to be trialled in UAE

 China's Suzhou Abogen Biosciences Co said its Covid-19 vaccine candidate using the messenger RNA (mRNA) technology and targeting the Omicron variant has obtained clinical trial approval in the United Arab Emirates (UAE).

With Friday's announcement, Abogen joins Pfizer/BioNTech and Moderna in trialing candidates modified specifically against Omicron, a highly transmissible variant.

https://www.malaysiakini.com/world/619925

Pfizer says COVID treatment Paxlovid fails to prevent infection of household members

 Pfizer on Friday said a large trial found that its COVID-19 oral antiviral treatment Paxlovid was not effective at preventing coronavirus infection in people living with someone who had been exposed to the virus.

The trial enrolled 3,000 adults who were household contacts exposed to an individual who was experiencing symptoms and had recently tested positive for COVID-19. They were either given Paxlovid for five or 10 days or a placebo.

Those who took the five-day course were found to be 32 per cent less likely to become infected than the placebo group. That rose to 37 per cent with 10 days of Paxlovid. However, the results were not statistically significant and thus possibly due to chance. 

“While we are disappointed in the outcome of this particular study, these results do not impact the strong efficacy and safety data we’ve observed in our earlier trial for the treatment of COVID-19 patients," Pfizer Chief Executive Albert Bourla said in a statement.

Pfizer said safety data in the trial was consistent with previous studies, which had shown the pills to be nearly 90 per cent effective at preventing hospitalization or death in COVID patients at high risk of severe illness when taken for five days shortly after symptom onset.

Pfizer said Paxlovid, which consists of two different antiviral drugs, is currently approved or authorized for conditional or emergency use in more than 60 countries across the globe to treat high-risk COVID-19 patients.

Sales of Paxlovid, part of a class of drugs known as protease inhibitors, are projected to reach $24 billion this year, according to Wall Street forecasts compiled by Refinitiv.

Shares of Pfizer, which fell 3 per cent in regular trading, were down another 1 per cent at $48.53 after hours.

https://www.ctvnews.ca/health/coronavirus/pfizer-says-covid-treatment-paxlovid-fails-to-prevent-infection-of-household-members-1.5882448

Omicron Sub-Lineages Can Dodge Immunity From Past Infection

 Two new sublineages of the Omicron coronavirus variant can dodge antibodies from earlier infection well enough to trigger a new wave, but are far less able to thrive in the blood of people vaccinated against COVID-19, South African scientists have found.

The scientists from multiple institutions were examining Omicron's BA.4 and BA.5 sublineages - which the World Health Organization last month added to its monitoring list. They took blood samples from 39 participants previously infected by Omicron when it first showed up at the end of last year.

Fifteen were vaccinated - eight with Pfizer's shot; seven with J&J's -- while the other 24 were not.

"The vaccinated group showed about a 5-fold higher neutralisation capacity ... and should be better protected," said the study, a pre-print of which was released over the weekend.

In the unvaccinated samples, there was an almost eightfold decrease in antibody production when exposed to BA.4 and BA.5, compared with the original BA.1 Omicron lineage. Blood from the vaccinated people showed a threefold decrease.

South Africa may be entering a fifth COVID wave earlier than expected, officials and scientists said on Friday, blaming a sustained rise in infections that seems to be driven by the BA.4 and BA.5 Omicron sub-variants.

Only about 30% of South Africa's population of 60 million is fully vaccinated.

"Based on neutralisation escape, BA.4 and BA.5 have potential to result in a new infection wave," the study said.

https://www.usnews.com/news/world/articles/2022-05-01/covids-new-omicron-sub-lineages-can-dodge-immunity-from-past-infection-study

Michigan Investigated Hundreds Of Doctors, Nurses Over COVID-Related Complaints

 by Alice Giordano via The Epoch Times (emphasis ours),

Hundreds of nurses and doctors, including a chief medical examiner, have been investigated by the state of Michigan on COVID-related allegations ranging from videotaping a wedding where some guests weren’t wearing masks to telling trick-or-treaters not to get the vaccine.

Authorities dismissed many of the complaints. Dozens are still pending, with a number referred for disciplinary action. Some have been referred to the Michigan Attorney General’s office for criminal prosecution.

An allergy and asthma specialist is the subject of one of the referrals sent to the attorney general. The complaint accuses the doctor of prescribing “a lethal dosage” of ivermectin.

Copies of the complaints, which total more than 500, were provided exclusively to the Epoch Times. The Pacific Justice Institute obtained the records through a FOIA request. The institute represents some of the accused nurses and doctors.

The Michigan Department of Licensing and Regulatory Affairs received and investigated the complaints. Those they have investigated have either been dismissed or referred to its enforcement division for disciplinary action or the AG’s office. Many are listed as still being listed “under board review.” The list provided to the institute includes complaints as recent as February 24, 2022.

One of the nurses the Pacific Justice Institute represents is Holly Austin, a college nursing professor who holds a doctorate in nursing.

She faced the revocation of her license by the Michigan Department of Licensing and Regulatory Affairs for speaking at a public school board meeting in December of 2021 as a parent against plans to reinstitute a mask mandate at her children’s school.

Dave Peters, a staff attorney with Pacific Justice Institute, told The Epoch Times he was shocked when the state continued its investigation into Austin even after he submitted a 100-page response to the state’s allegations that she was spreading misinformation.

“I remember not long ago that such actions by government authorities or anybody else would have had the entire journalist community howling about suppression and chilling free speech, ” said Peters, who also holds a master’s degree in medicine.

According to documents Peters provided to The Epoch Times, it took the state more than a year to close the investigation against Austin. The state concluded in a March 3, 2022 letter “that following a thorough review and investigation,” it had “determined a violation of the Public Health Code cannot be substantiated.”

More than 200 doctors and nurses found themselves under investigation just for expressing concerns about the COVID vaccine or for not wearing or promoting the wearing of masks. One doctor was reported for shaking hands with someone who wasn’t wearing a mask; another was the subject of a complaint for claiming he had a bad reaction to the COVID vaccine.

In February, Ljubisa Dragovic, Chief Medical Examiner for Oakland County, found himself under investigation by the state for performing autopsies without wearing a mask.

“When you are working in an environment with deceased individuals there is no active sneezing or coughing on the part of the cadavers. It was nonsense,” Dragovic told The Epoch Times, “you can’t get or give COVID to a dead person.” Dragovic said he couldn’t wear a mask because his glasses would fog up, and he couldn’t see what he was doing.

“The last thing you want to be is blinded while using a sharp scapula,” he said.

Dragovic, who is fully vaccinated and believes in wearing masks around live patients and co-workers, said he spent about two hours answering questions from investigators for the Michigan Medical Licensing Board.

According to Dragovic, another medical examiner filed the complaint. The person was “totally crazed with fear over COVID,” Dragovic said. That doctor was hired at the height of the pandemic to perform autopsies but refused to do so out of fear he would contract COVID-19, even locking himself in his office at times. He eventually quit, according to Dragovic.

The complainant only filed the allegation a year later after Dragovic refused to give the doctor a job reference.

Peters says the case is an example of how the state investigations had nothing to do with keeping the public safe.

“This was used to kill free speech to intimidate people into submission,” he said, “period.”

Dozens of the complaints were againt doctors who issued mask waivers to children. Three nurses were accused of falsifying proof of vaccines, including one who allegedly did so for a friend for a cruise.

The licensing board referred complaints against two physicians and two chiropractors to the Michigan Attorney General’s Office for “not following COVID-19 safety precautions.”

The board investigated several physicians and nurses for either promoting or prescribing ivermectin or hydroxychloroquine.

The complaint against Austin cites an email she wrote to the Brighton School Board that included a compilation of research she had conducted on the harm of wearing masks. She cited over 200 studies.

“I implore you to be informed of the current literature regarding masks and their ineffectiveness to decrease the transmission of COVID-19, the potential and inherent harms of masks on our pediatric population, and the short term and long term sequelae to our youth with continued mask mandates,” Austin wrote.

Michigan Department of Licensing and Regulatory Affairs did not respond to inquiries from The Epoch Times about the investigations.

https://www.zerohedge.com/covid-19/michigan-investigated-hundreds-doctors-nurses-over-covid-related-complaints

Does selenium really slow aging?

 Selenium is a trace mineral, which means the body only requires it in very small amounts. It is naturally present in many foods and is also available as a dietary supplement.

The majority of selenium from our diet gets stored in muscle tissue, though the thyroidTrusted Source is the organ with the highest concentration.

Selenium is an important componentTrusted Source of enzymes and proteins — known as selenoproteins — that play a key role in reproduction, thyroid hormone metabolism, and DNA synthesis.

Selenoproteins also act as powerful antioxidants that help protect against damaging particles in the body called free radicals.

Free radicalsTrusted Source are unstable atoms produced naturally in the body as a byproduct of normal functions within the body. They cause damage to cell membranes and DNA. Over time, this can lead to inflammation, premature skin aging, and a host of age-associated diseases.

Anti-aging benefits

Biological agingTrusted Source is a complex process that involves molecular damage, metabolic imbalance, immune system changes, and increased susceptibility to environmental stressors and disease.

According to a reviewTrusted Source from 2018, selenium can fight aging and prevent age-related health issues, such as tumors, cardiovascular disease, and neuropsychiatric disorders. Some researchers also believe that selenium can reduce chronic inflammationTrusted Source, which is closely related to aging.

According to some research, selenoproteins are primarily responsible for many of the health benefits of selenium.

For example, one 2021 review found that selenoproteins play a key role in controlling and removing misfolded proteinsTrusted Source, which accumulate as we age. Specialists note that the accumulation of misfolded proteins is a common characteristic of aging and age-related diseases, including type 2 diabetes and Alzheimer’s disease.

Experts also believe that selenium protects the skin against ultraviolet (UV) oxidative stress by stimulating the selenium-dependent antioxidant enzymes glutathione peroxidase (GPx) and thioredoxin reductaseTrusted Source (TDR). TDR is located in the plasma membrane of epidermal keratinocytes. This may potentially combat aging skin caused by UV exposure.

Moreover, a newer study from 2020 found that increased dietary intakes of selenium are associated with longer telomeres. This study found that every 20 microgram increase in dietary selenium was associated with a 0.42% longer telomere length in participants over the age of 45.

Telomeres are “protective caps” located on the ends of our chromosomes that affect how quickly cells age. Some experts consider telomere length as an informative biomarker of aging.

ResearchersTrusted Source also believe that higher levels of selenium are associated with longevity. The all-cause mortality of older adults with low selenium levels is significantly higher than that of the elderly with a high level of selenium.

For example, centenarians often appear to have higher systemic levels of selenium and iron while having lower levels of copper than other older people.

However, it is important to note that results remain conflicting and more research on the topic is needed. Some studies — such as the one referred to above — suggest that low levels of selenium may actually promote longevity.

Other health benefits

Selenium may also play an important role in the protection against certain age-related diseases.

Heart disease

One meta-analysisTrusted Source found that people with lower selenium levels are at a higher risk of coronary heart disease. In contrast, a review Trusted Sourceof trials that used only selenium supplementation for the primary prevention of heart disease found no statistically significant effects of selenium on both fatal and nonfatal cardiovascular events.

Although some research appears promising, there is not enough evidenceTrusted Source to support the routine use of selenium supplements, especially in those who are obtaining enough from food to prevent heart disease at this time.

Cancer

There is a notion that selenium may play a role in cancer prevention thanks to its ability to protect cells against DNA damage and mutations. However, the evidence around this remains conflicting.

According to a 2018 reviewTrusted Source of 83 studies, there is no solid research to suggest selenium from diet or supplements prevents cancer in humans.

In fact, some trialsTrusted Source suggest that selenium supplementation may increase the risk of non-melanoma skin cancer and type 2 diabetes.

Thyroid disease

Selenium plays a key role in thyroid function. Some studiesTrusted Source suggest that having optimal selenium levels can protect against thyroid disease and preserve overall health.

However, according to the Office of Dietary SupplementsTrusted Source, additional research is needed to determine whether selenium supplements can treat or prevent thyroid disease.

Cognitive decline

Because serum selenium levels decline with age, marginal or deficient selenium concentrations may be associated with age-related declines in brain functionTrusted Source. Experts believe this might be due to selenium’s antioxidant properties.

Still, more research is needed to determine if selenium supplementation can help treat or prevent age-related cognitive decline in older adults.

Selenium supplement?

Overall, research remains conflicting regarding selenium supplementation and the effect of selenium on aging.

According to the 2018 review discussed above, most studies point to selenium supplementation having anti-aging properties and preventing aging-related diseases. However, more studies are needed to clarify its role.

At this time, there is no solid evidence that selenium supplementation benefits a person who is not at risk for deficiency.

A selenium deficiency is rare in the United States because of the selenium-rich soil found throughout North America.

Still, certain groups are at risk for selenium deficiency, including:

• people living with HIV
• people with kidney failure requiring hemodialysis
• people who live in low-selenium regions, including some European countries, Russia, and China.

The risk is further increased for people living in low-selenium areas who follow a vegetarian or vegan diet.

Selenium deficiency can weaken cells’ ability to grow and divide, which can contribute to aging. It can also lead to delayed wound healing, cataract development, and loss of color.

Food sources

Most adults need 55 microgramsTrusted Source (mcg) of selenium per day. Pregnant women, however, should consume 60 mcg. During lactation, selenium needs to further increase to 70 mcg.

Since the human body does not generate its own selenium, it is essential to get optimal amounts from the diet, in order for it to benefit overall health.

Thankfully, selenium is found in a wide variety of foods that can be easily incorporated into a person’s diet.

Because selenium is found in soil, its levels in food will be based on how much selenium was in the soil where the food was grown.

Brazil nuts, seafood, and organ meats are among the highest dietary sources of selenium. For example, one ounce of brazil nuts has 544 mcgTrusted Source of selenium or 989% of the recommended Daily Value (DV).

Other good dietary sources of selenium include:

• yellowfin tuna
• halibut
• sardines
• beef
• ham
• shrimp
• cottage cheese
• brown rice
• boiled eggs
• whole wheat bread
• beans/lentils.

Potential risks

If a person consistently exceeds the recommended upper limit of 400 mcgTrusted Source of selenium through foods or supplements, it can cause adverse health effects.

One of the first signs of excessive selenium intake is a garlic smell on the breath and a metallic taste in the mouth.

Other signsTrusted Source of chronically high selenium intake are:

• hair and nail loss or brittleness
• skin lesions
• mottled or decaying teeth
• nausea
• diarrhea
• fatigue
• irritability.

Taking megadoses of selenium can lead to acute selenium toxicityTrusted Source, which can lead to acute respiratory distress syndrome, severe gastrointestinal and neurological symptoms, kidney failure, cardiac failure, and — in extreme cases — death.

The bottom line

Selenium is an important mineral that is needed for many important functions within the body. There is also limited evidence that it may provide several different health benefits.

Selenoproteins are powerful antioxidants that can help protect against damage caused by free radicals that lead to aging and age-related health conditions.

At this time, there is no evidence that selenium supplements can slow or prevent aging. However, it is important to include optimal amounts of selenium in the diet because it does play a role in neutralizing free radicals and reducing inflammation, both of which can contribute to premature aging.

If you believe you have a selenium deficiency or are considering taking selenium supplements, be sure to speak with your healthcare provider.

https://www.medicalnewstoday.com/articles/does-selenium-really-slow-aging