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 hasinked a $17.5m up-front deal with Orchard Therapeuticsfor 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
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 $16.5bn. The approval was given on the condition that a confirmatory trial be run, but remarkably the study is not required to read out until 2030 at the latest. Aduhelm’s approval opened the floodgates in Alzheimer’s andEli Lilly has confirmed it intends to file its similarly acting donanemablater this year. Elsewhere, three complete response letters were dished out, including one for Orphazyme’s arimoclomol in Niemann-Pick disease, with the FDA requesting further clinical data. The Pdufa for Ascendis’s paediatric growth hormone deficiency treatment TransCon hGH was extended; three other decisions were also delayed. The agency also missed the deadline for Abbvie's Rinvoq in two indications owing to ongoing safety concerns with the Jak class. Delays for other Jak inhibitors will likely continue into the next few months as the regulator continues to review the safety profile of Pfizer's Xeljanz (Go or no go? Ardelyx and Chemocentryx among those waiting FDA decisions, July 1, 2021).
Notable first-time US approval decisions in June
Project
Company
Indication(s)
2026e sales by indication ($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
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)
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 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."
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.”
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.
The White House is deploying Covid-19 response teams across the United States focused on combatting the highly contagious delta variant, the Biden administration announced Thursday.
The teams, comprised of officials from the Centers for Disease Control and Prevention and other federal agencies, will work with communities at higher risk of experiencing outbreaks and will focus on increasing the rate of Covid-19 vaccinations, White House Covid czar Jeff Zients said during a White House news briefing on the pandemic.
The teams will also increase testing to expand detection of the virus, facilitate contact tracing and provide therapeutics to help treat those who become infected, he said, adding the government is ready to provide additional personnel.
There are 1,000 counties in the U.S. that have vaccination coverage of less than 30%, CDC Director Dr. Rochelle Walensky said at the briefing. These counties, primarily in the South and Midwest, are the most vulnerable to the variant, she said.
“To be clear, the federal government stands ready to meet the moment and work with our state partners to respond to the delta variant,” Zients said.
“As we continue to work with communities across the country to get more shots in arms, we will also be working with governors and state and local health authorities to identify and address the needs on the ground in places with emergency outbreaks,” he added.
The Biden administration’s comments come just ahead of the Fourth of July weekend, when many Americans are expected to gather for fireworks, barbeques and other large, in-person activities.
Delta, first identified in India but now in at least 96 countries, is expected to become the dominant variant of the disease in the U.S. The prevalence of the delta, estimated to be about 60% more transmissible than the alpha variant first found in the U.K., is doubling in the U.S. about every two weeks, according to the CDC.
Health officials say there were reports that the delta variant also causes more severe symptoms, but that more research is needed to confirm those conclusions. Still, there are signs the delta strain could provoke different symptoms than other variants.
This is a “highly contagious virus,” said Dr. Paul Offit, a pediatrician and vaccine advocate who has served on advisory panels for both the CDC and the Food and Drug Administration.
“We need to vaccinate now. I mean get everyone vaccinated now because these mutations are going to continue to occur,” he said. It’s only July but “as we head into the fall and early winter you’re going to see a surge and there are too many people in this country who are still unvaccinated.”
Delta accounts for around 26% of Covid cases in the U.S., the CDC has estimated. Dr. Anthony Fauci, the White House’s chief medical advisor, has called the variant the “greatest threat” to the nation’s attempt to eliminate Covid-19.
The WHO has said the variant is the fastest and fittest coronavirus strain yet, and it will “pick off” the most vulnerable people, especially in places with low Covid vaccination rates. It recently urged everyone, including vaccinated people, to continue to wear masks as the variant spreads.
In some regions of the country, nearly one in two sequences is the delta variant, Walensky said Thursday. As the variant spreads, officials expect to see an increase in transmission unless states can vaccinate more people, she added.
As of Thursday, more than 181 million Americans, or 54.6% of the U.S. population, have had at least one dose of a Covid vaccine, according to data compiled by the CDC. More than 155 million Americans are fully vaccinated, according to the CDC.
“The delta variant is predicted to be the second most prevalent variant in the United States, and I expect that in the coming weeks it will eclipse the alpha variant,” she said, urging those with symptoms to get tested for Covid.
Oncology Pharma Inc. (OTC PINK:ONPH) Oncology Pharma, Inc. (the "Company") is developing a program to establish the use of its license utilizing NR2F6 agonists and antagonists coupled with the proprietary drug delivery systems in the treatment of various disorders including human pancreatic cancer and colon cancer. The work the Company is contracting to conduct is intended to do pre-clinical trials leading into seeking FDA approval for the combined efforts. Our team of industry experts and advisors have the expertise to lead the Company to efficiently conduct this next phase of development.
The developing program will allow Oncology Pharma to begin its own path towards producing proprietary intellectual property, for the pursuit and development of new therapies. The Company's established portfolio of licensing agreements is expected to allow the company the ability to develop its own innovations to stand out amongst its peers.
