Covid Gamma Variant Rises in Washington State

 On top of a historic heat wave, the Pacific Northwest has been hit with a rise in COVID-19 cases caused by the Alpha, Delta, and Gamma variants. And while much of the world is focused on Delta, or B.1.617.2, government officials in Washington state are particularly wary of Gamma (P.1).

Washington state's leading COVID-19 strain remains Alpha (B.1.1.7), first detected in the U.K. But according to recent data released by the state's Department of Health (DOH), cases caused by Gamma reached 16.3% in mid-June -- a decrease from a high of 20.6% in May. Delta cases increased by more than 10% from May to June, now making up 17.6% of infections in the state -- all while Alpha cases continue to slowly dwindle.

Although the Delta variant has eclipsed Gamma cases in Washington in recent weeks, state epidemiologist Scott Lindquist, MD, MPH, has continued to express his worries about Gamma's detrimental impact.

"Our Delta variant is not as aggressive, it's not causing as many hospitalizations or deaths as would be predicted, but the P.1 tends to be causing more hospitalizations and deaths," Lindquist said in a DOH briefing about the state's June 30 reopening.

The Gamma variant was, in fact, associated with the highest number of hospitalizations and deaths in comparison to any other strains of COVID-19, including Alpha and Delta, according to the DOH report.

Notably, Gamma was detected in 17% of breakthrough infections after vaccination, making it second overall -- after Alpha -- in vaccine breakthroughs.

Despite these data, Lindquist assured that "all the vaccines we have in Washington state still show effectiveness for these variants," as Washington's DOH continues its vaccination campaign. "It's much more of a risk to be unvaccinated in this state right now than it is any concern for the vaccine not working against these variants," he said.

Gamma was first identified among travelers from Brazil at the beginning of January during a routine screening at an airport in Japan. When Gamma became the dominant strain of SARS-CoV-2 in Brazil not long after, both the World Health Organization and the CDC designated Gamma as a variant of concern. Now, it has been identified in at least 37 countries and 31 U.S states.

After Manaus, the capital of Brazil's Amazonas region, was struck with a wave of COVID cases in the spring of 2020, certain studies suggested that the city may have reached herd immunity. However, the Gamma variant caused a resurgence of SARS-CoV-2 infections in Manaus in January of this year.

A study of Manaus's COVID resurgence found that Gamma could be nearly twofold more transmissible than other variants from the same lineage. Data from Manaus indicated that "P.1-infected adult individuals are more infectious than those harboring non-P.1 viruses," wrote Felipe Gomes Naveca, of the Leonidas and Maria Deane Institute's Laboratory of Ecology of Communicable Diseases, and colleagues.

Gamma closely resembles the lineage of Beta (B.1.351), which was first detected in South Africa and is now a variant of concern. Because Beta and Gamma share some of the same mutations on the coronavirus spike protein, they're both capable of overcoming the immunity that individuals may have developed after being infected by other strains.

Like Beta, Gamma contains the N501Y and K417T mutations, both of which give the virus a tighter grasp on human cells. It also carries E484K, a mutation known to help the virus evade certain types of antibodies. Vaccines, therefore, may offer less protection against the Gamma variant than others.

https://www.medpagetoday.com/special-reports/exclusives/93415

Catalyst, Zogenix, Rigel and Pfizer kick off pharma's July price hikes

 Pharma companies haven’t shied away from raising prices even in the midst of a global pandemic. And now that the world is slowly beginning to creep out of the crisis, this July doesn’t appear to be any different. 

To kick off the month, a slate of drugmakers have already raised prices on 32 medicines by an average of 3.6%, GoodRx reports. It’s still early in the counting, and it’s likely that pharma is just getting started if previous trends are any indication.

The early start has consisted mostly of smaller drugmakers, in many cases dealing with rare disorders, such as Zogenix, Rigel Pharmaceuticals, Recordati Rare Diseases, Catalyst Pharmaceuticals, Azurity Pharmaceuticals and others. 

Zogenix’s 9.5% increase for its rare childhood epilepsy drug Fintepla marks the largest hike so far. Fintepla became Zogenix’s first commercialized product nearly a year ago when it scored an FDA nod to treat seizures associated with Dravet syndrome, entering the market with a $1,278 list price for a 30 mL bottle. 

Then there’s Catalyst’s controversial drug Firdapse for patients with a rare neuromuscular disorder called LEMS. The company faced fierce backlash after launching the treatment at $375,000 per year, even though another company had been giving it away under the FDA's compassionate use. 

Catalyst will increase Firdapse’s list price by 4.5%, GoodRx reports. Meanwhile, Rigel’s first and only FDA-approved drug Tavalisse, used to treat chronic immune thrombocytopenia, will see a 5% increase. 

Some drugs on the list already grew in price earlier this year. For instance, Recordati had raised the price of Isturisa, approved to treat Cushing’s disease, by 9% in January. The company kicked off July with another 5% hike, GoodRx reports. Specialty pharma company TerSera Therapeutics upped its chronic pain drug Prialt another 4% after doing so in January. 

In January, pharma hiked prices by an average of 4.5% on more than 800 drugs, according to GoodRx's tally. Pfizer accounted for a significant portion of them and has already kicked off this round with 1.5% bumps for acute myeloid leukemia drug Mylotarg and acute lymphoblastic leukemia treatment Besponsa. 

The increases come as the industry faces looming uncertainty over drug pricing reform in the U.S. While President Joe Biden has supported changes that would allow Medicare to negotiate prices for high-cost drugs, among other measures, the president left drug pricing provisions out of his American Families Plan. That effectively moved the discussion over to a divided Congress, where pricing reforms have languished for years.

But reform chatter has recently resurfaced after the FDA’s controversial approval of Biogen’s Alzheimer’s drug Aduhelm. Some lawmakers are concerned that the treatment, priced at roughly $56,000 per year, could severely inflate Medicare’s spending by billions. 

https://www.fiercepharma.com/pharma/pfizer-zogenix-catalyst-rigel-kick-off-pharma-s-july-price-hikes-report

Pharming turns to gene therapy for next-gen HAE therapy

 Hereditary angioedema (HAE) has gone from an intractable, life-threatening, rare disease to a field with eight marketed drugs in just 13 years. If Pharming has its way one of the next additions could be a gene therapy. The Dutch group has inked a $17.5m up-front deal with Orchard Therapeutics for worldwide rights to OTL-105. OTL-105 works by inserting one or more functional copies of the SERPING1 gene into patients' own hematopoietic stem cells ex vivo, enabling production of the C1-INH protein HAE patients lack. Pharming could well steal a march on market leader Takeda by investing in gene therapy now; the Japanese giant, whose Takhzyro is forecast to hit blockbuster status this year, does not appear to have a stake in any such technology in HAE. Nearer term-innovation in HAE includes Kalvista and Pharvaris's oral projects in both the acute and prophylactic space. Several groups are looking at longer-acting mechanisms, including CSL with its once monthly MAb, while in vivo gene editing and RNAi projects are in early stages elsewhere. Should these approaches succeed a less convenient gene therapy could well prove useful only for the most severe cases, but with much work still to be done that remains a debate for the future. 

Selected long-acting and cell and gene therapy HAE projects
	Company	Description
Phase III
Garadacimab	CSL	Once-monthly MAb for prophylaxis
Phase II
IONIS-PKK-LRx	Ionis Pharmaceuticals	Once-monthly antisense for prophylaxis
Pre-clinical
ALN-F12	Alnylam Pharmaceuticals	RNAi targeting coagulation factor XII
BMN 331	BioMarin Pharmaceutical	AAV5-based gene therapy
NTLA-2002	Intellia Therapeutics	Prekallikrein (PKK) antisense
Un-named	Regenxbio	AAV gene therapy
Un-named	Orchard/Pharming	Autologous hematopoietic stem cell gene therapy
Source: Evaluate Pharma.  https://www.evaluate.com/vantage/articles/news/snippets/pharming-turns-gene-therapy-next-gen-hae-therapy

FDA approval tracker: June

 Last month the US regulator gave a controversial thumbs-up to Biogen’s Alzheimer’s drug Aduhelm, and the decision boosted the company’s market cap by $16.5bn. The approval was given on the condition that a confirmatory trial be run, but remarkably the study is not required to read out until 2030 at the latest. Aduhelm’s approval opened the floodgates in Alzheimer’s and Eli Lilly has confirmed it intends to file its similarly acting donanemab later this year. Elsewhere, three complete response letters were dished out, including one for Orphazyme’s arimoclomol in Niemann-Pick disease, with the FDA requesting further clinical data. The Pdufa for Ascendis’s paediatric growth hormone deficiency treatment TransCon hGH was extended; three other decisions were also delayed. The agency also missed the deadline for Abbvie's Rinvoq in two indications owing to ongoing safety concerns with the Jak class. Delays for other Jak inhibitors will likely continue into the next few months as the regulator continues to review the safety profile of Pfizer's Xeljanz (Go or no go? Ardelyx and Chemocentryx among those waiting FDA decisions, July 1, 2021).

Notable first-time US approval decisions in June
Project	Company	Indication(s)	2026e sales by indication ($m)	Outcome
Aduhelm (aducanumab)	Biogen/Eisai	Alzheimer's disease	3,907	Approved (accelerated)
Transcon hGH (lonapegsomatropin)	Ascendis	Paediatric growth hormone deficiency	1,407	Extended to Sept 25
PF-06482077/ 20vPnC/ Prevnar 20	Pfizer	Pneumonia	1,037	Approved
Lybalvi (ALKS 3831)	Alkermes	Schizophrenia and bipolar I disorder	380	Approved
Eohilia/ TAK-721	Takeda	Eosinophilic esophagitis	350	No decision yet
Brexafemme (ibrexafungerp/SCY-078)	Scynexis	Vulvovaginal candidiasis	302	Approved
Miplyffa (arimoclomol)	Orphazyme	Niemann Pick disease type C	297	CRL (more data needed)
IV Tramadol	Avenue	Acute pain	273	CRL (second)
VP-102	Verrica	Molluscum contagiosum	271	Extended to Sept 23
Nexobrid	Mediwound/ Vericel	Treatment of severe thermal burns	165	CRL (CMC)
Tanezumab	Pfizer/Lilly	Moderate-to-severe osteoarthritis pain	155	No decision yet
Ryplazim	Liminal	Congenital plasminogen deficiency	66	Approved
StrataGraft	Mallinckrodt	Adults with deep partial-thickness thermal burns	59	Approved
Rylaze (JZP-458)	Jazz	Component of chemo regimen to treat ALL or lymphoblastic  lymphoma in patients who are allergic to  E. coli-derived asparaginase	33	Approved
Rezipres (Ephedrine injection/ET-203)	Eton/Sintetica	Hypotension	37	Approved
Verkazia	Santen	Keratoconjunctivitis in patients aged 4-18	-	Approved
Tembexa (brincidofovir)	Chimerix	Smallpox (adult and paediatric patients)	-	Approved (~1 month early)
Source: Evaluate Pharma & company releases.

 

Advisory committee meetings in June
Project	Company	Adcom date	Indication	2026e sales by indication ($m)	Outcome	Note
Retifanlimab (INCMGA0012)	Incyte/Macrogenics	June 24	Adult patients with locally advanced or met squamous carcinoma of the anal canal who have progressed on or who are intolerant of platinum-based chemotherapy.	53	13-4 voted for confirmatory study	Anti-PD-1 MAb, Pdufa July 25
Source: Evaluate Pharma & FDA adcom calendar.

 

 

Supplementary and other notable approval decisions in June
Product	Company	Indication (clinical trial)	Outcome
Rinvoq	Abbvie	Psoriatic arthritis (Select-PsA 1, Select-PsA 2)	Missed (FDA citing review of Pfizer's Xeljanz)
Rinvoq	Abbvie	Ankylosing spondylitis (Select-Axis 1)	Missed (FDA citing review of Pfizer's Xeljanz)
Ruxolitinib cream	Incyte	Atopic dermatitis (TruE-AD1, TruE-AD2)	Extended to Sept 21
Jakafi	Incyte/Novartis	Paediatric patients with steroid-refractory GVHD (Reach3)	Extended to Sept 22
Cosentyx	Novartis	Moderate-to-severe plaque psoriasis in children and adolescents aged 6 to <18 years (NCT03668613, NCT02471144)	Approved
Ultomiris	Astrazeneca	Children and adolescents with PNH	Approved
Trikafta	Vertex	Children aged 6 to 11 who have at least one F508del mutation in the CFTR gene or a mutation in the CFTR gene that is responsive based on in vitro data (NCT03691779)	Approved
Ayvakit	Blueprint	Advanced systemic mastocytosis (Pathfinder, Explorer)	Approved
Solosec	Lupin	Treatment of trichomoniasis  in adults and adolescents	Approved
Wegovy (semgalutide 2.4mg)	Novo Nordisk	Obesity (Step 1, 2, 3, 4)	Approved
Epclusa	Gilead	Expansion of the paediatric indication for chronic hepatitis C (NCT03022981)	Approved
Pradaxa (oral pellets)	Boehringer Ingelheim	Blood thinner for children aged 3 months to less than 12 years old (NCT01895777, NCT02197416)	Approved
Alecensa	Roche	1st-line Alk-positive NSCLC (Bfast)	No decision yet
Source: Evaluate Pharma & company releases.

 

FDA Covid-19 EUAs
Product	Company	2026e sales by indication ($m)	Note
Actemra	Roche	-	Treatment of hospitalized adults and paediatric patients
Source: Evaluate Pharma & company releases. https://www.evaluate.com/vantage/articles/news/snippets/us-fda-approval-tracker-june-0

What Extending the Lifespan of Dogs Could Mean for Human Aging

 As an animal care technician, Cherie Cornmesser has seen first-hand the ways that animals can help to advance medical research, sometimes leading to treatments for many conditions and diseases in humans. So, when she saw an opportunity to sign up her dog, Kylo, a 4-year-old shiba inu, for a national dog-aging study, led by the National Institutes of Health, Cornmesser didn't hesitate.

Cherie Cornmesser's dog, Kylo, a 4-year-old shiba inu, is participating in the Dog Aging Project  |  Credit: Suzanne Nuss

Shibas are a fairly uncommon dog breed, and the bigger pool of dogs that are included in the study, the better the potential outcomes, said Cornmesser, 51, who works with primates in a neuroscience lab at the University of Pittsburgh.

"I'm very proud of the animals I work with in the lab and am just as proud that my canine companion can also help scientists to help find answers that will lead to better outcomes and quality of life for many," she said. 

The Dog Aging Project started with 10,000 dogs in late 2019, and now has almost 30,000 dogs, which researchers aim to follow for at least five years and hopefully their lifespan, said Kate Creevy, the project's chief veterinary officer and associate professor in the Department of Small Animal Clinical Sciences at Texas A&M University.

The research is the largest study of companion dogs ever performed, and investigators are looking for more dog owners to volunteer.

The goal is to understand why some dogs — like some people — age well, and why other dogs — like other people — age poorly, Creevy said. Dogs live shorter lives than their humans, with smaller breeds living up to 18 years.

What's interesting, Creevy said, is that larger dogs have a short time as a puppy, grow into adulthood more quickly and spend more time as a senior. Small dogs stay in that healthy middle age window for a longer time. Researchers just aren't sure why.

But hopefully, some of the answers from the canine companions will help extend and improve their human owners' lives as well.

What Researchers Want to Know

Volunteers answer extensive surveys of 300 to 400 questions about their dog's life, from where they sleep to how much they sleep, what kind of toys they play with, how much and what kind of food they eat and how many times a day. Researchers follow up at least once a year for the rest of the dog's life.

Kylo  |  Credit: Cherie Cornmesser

"Sometimes dogs are fed one time a day, or sometimes it's three times or the food is left out all day. There's everything in between, and we're looking to see what shape they're in and study what's different among the dogs and how their life unfolds," said Creevy.

"It's not that different from human aging and intermittent fasting, and looking at the dogs who are fed once a day — is there any benefit versus the dogs who are fed three meals a day."

Researchers aren't just looking at one thing across the study. They may look at a particular disease across one breed or aging across a particular size of dog.

One of the areas of focus is called the "body condition score." It's kind of like the body mass index or BMI for dogs. It's a score of 1 to 9 that all veterinarians use to rank all breeds of dogs based on size, 1 being the skinniest and 9 being the fattest.

Researchers are looking at whether an animal's body condition score is related to its lifespan and whether, like studies in fruit flies and mice, leaner species live longer. 

Some Dogs Will Be Enrolled in a Drug Trial  

Another area of interest is the drug Rapamycin, an immunosuppressant medication used in people to prevent organ rejection in transplant patients (interestingly, it was originally found in a soil sample at Easter Island.) At low doses, the drug has been found to have anti-aging properties and prevent obesity.

As part of the Dog Aging Project, several hundred dogs are part of a clinical trial where some receive a very low dose of the drug and others receive a placebo. Scientists are looking to see if Rapamycin changes the dogs' metabolism in a way that resembles caloric restriction.

In similar rodent studies, mice retained muscle mass and cognitive function, but at a cellular level they experienced the anti-aging benefits typically gained from restricting calories, said Creevy.

During the first pilot study testing Rapamycin in dogs, there was a small but noticeable improvement to the animals' heart function. But the second study at a lower dose did not produce the same results.

Now, researchers are working on a third study on a larger sample of dogs using a low-dose model similar to the first round that would treat the dogs for one year and then follow them for two more.

The anti-aging benefits of Rapamycin are well known, but the drug has some serious side effects in humans at higher doses. It is currently being studied in humans to treat different kinds of cancer and was suggested as a treatment for COVID-19 as well.

"We get requests from people (who want to take the drug) to prescribe it to their dogs all the time, and we say no," said Creevy. "But there are definitely people who have chosen to take it."

https://www.nextavenue.org/aging-study-dogs/

Number Of US Truck Drivers Sidelined Due To Substance Abuse Violations Passes 60K

 By John Gallagher of FreightWaves

The number of U.S. truck drivers sidelined due to substance abuse violations has surpassed 60,000 and continues to climb by roughly 2,000-3,000 per month, according to federal data. The latest monthly report by the Drug and Alcohol Clearinghouse, administered by the Federal Motor Carrier Safety Administration since January 2020, revealed that 60,299 CDL holders have a drug or alcohol violation recorded in the clearinghouse as of June 1, up from 57,510 as of May 1 and up from 18,860 recorded in the clearinghouse as of May 1, 2020.

Drivers with at least one substance abuse violation are barred from operating a commercial truck until they complete a return-to-duty process, which includes providing a negative follow-up test result. The percentage of drivers who are completing the RTD process has steadily increased over the past year, however, from 5.2% as of May 1, 2020, to 22.1% as of May 1, 2021.

Marijuana consistently tops the list of substances identified in positive drug tests, far outpacing cocaine and methamphetamine, the second- and third-highest drug violations, respectively, among CDL holders.

The number of violations now recorded in the clearinghouse stands out for another reason: It’s coincidentally just a few hundred shy of an estimated number of drivers needed to fill a shortfall of commercial drivers to keep pace with freight demand.

“According to a recent estimate, the trucking industry needs an additional 60,800 truck drivers immediately — a deficit that is expected to grow to more than 160,000 by 2028,” testified American Trucking Associations President and CEO Chris Spear at a Capitol Hill hearing on freight mobility in May.

“In fact, when anticipated driver retirement numbers are combined with the expected growth in capacity, the trucking industry will need to hire roughly 1.1 million new drivers over the next decade, or an average of nearly 110,000 per year.”

Scopelitis Consulting Co-Director Sean Garney pointed out that the growing number of prohibited drivers is not a bad thing from a safety standpoint.

“The database is doing what it’s supposed to do, which is identify those who should not be driving,” Garney told FreightWaves. “Losing drivers due to positive drug tests may not necessarily be a good thing for truck capacity, but I think what many others in this industry also care about is safety.”

https://www.zerohedge.com/economics/number-us-truck-drivers-sidelined-due-substance-abuse-violations-has-surpassed-60000

Alector Shares Jump On $2.2B Immuno-Neurology Development Pact With Glaxo

 

• Alector Inc (NASDAQ: ALEC) and GlaxoSmithKline plc (NYSE: GSK) have announced a global collaboration for the development and commercialization of two monoclonal antibodies designed to elevate progranulin (PGRN) levels.

• PGRN is a crucial regulator of immune activity in the brain with genetic links to multiple neurodegenerative disorders.

• Alector will receive $700 million in upfront payments and is eligible to receive up to an additional $1.5 billion in milestone payments.

• Alector will lead the global development of AL001 and AL101 through Phase 2 proof-of-concept.

• After that, Alector and GSK will share development responsibilities for all late-stage clinical studies for AL001 and AL101.

• All costs for global development will be divided between the two companies, and will be jointly responsible for commercialization in the U.S. and will share profits and losses.

• Alector will lead commercial efforts associated with AL001 in orphan indications, and GSK will lead the commercialization of AL101 in Alzheimer's and Parkinson's disease.

• Outside the U.S., GSK will be responsible for the commercialization of AL001 & AL101, and Alector will be eligible for tiered royalties.

https://finance.yahoo.com/news/alector-shares-jump-2-2b-122617268.html