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Tuesday, August 18, 2020

FDA accepts AstraZeneca application for new dosing regimen for Imfinzi

Under Priority Review status, the FDA has accepted AstraZeneca’s (NYSE:AZN) supplemental marketing application seeking approval of a four-week, fixed-dose regimen for PD-L1 blocker Imfinzi (durvalumab) for non-small cell lung cancer and bladder cancer.

The current regimen is weight-based (10 mg/kg) dosing every two weeks.


Tiziana nabs new U.S. patent for expanded use of Foralumab

Tiziana Life Sciences (NASDAQ:TLSA) soars 26% premarket on the heels of the announcement that the USPTO has granted the company a patent on use and methods of treatment of Crohn’s disease with Foralumab, a fully human monoclonal antibody, and all other anti-CD3 monoclonal antibodies (mAb).

The composition-of-matter and use patent will be published on September 1 as Patent No. 10,759,858.


Novo teams up with Evotec in kidney diseases

Novo Nordisk (NYSE:NVO) will collaborate with Evotec SE (OTCPK:EVOTF) on the discovery and development of novel therapies for the treatment of chronic kidney disease (CKD).

The companies will jointly identify and develop new targets based on comprehensive medical and molecular datasets of thousands of CKD patients. They will share responsibilities during drug discovery and preclinical development while Novo will be responsible for clinical development and commercialization.

Novo will pay Evotec an upfront fee, research funding, up to €150M in milestones per product and tiered royalties on net sales. Additional financial terms remain confidential.


Monday, August 17, 2020

More Evidence Heartburn Drug May Help COVID-19 Patients

More data from observational studies, this time in hospitalized patients, indicated that famotidine (Pepcid AC), which is used to treat heartburn, was associated with improved clinical outcomes in COVID-19 patients.

Use of famotidine in a small group of 83 patients was associated with a lower risk of in-hospital mortality and a combined outcome of death and intubation, reported Jeffrey Mather, MS, of Hartford Hospital in Connecticut, and colleagues.

Moreover, famotidine use was also associated with lower levels of serum markers indicating severe disease, the authors wrote in the American Journal of Gastroenterology.

Famotidine is a histamine-2 receptor antagonist. The authors noted the mechanism by which famotidine might improve COVID-19 outcomes is currently unknown, but hypothesized it might work via “inverse-agonism” of the histamine-2 receptor, which implies SARS-CoV-2 is “at least partially mediated by pathological histamine release,” the authors said.

The drug was tied to significant reductions in in-hospital death and a combined death and intubation outcome in hospitalized patients in China, as well as an improvement in symptoms in a small case series of non-hospitalized patients, mostly in the U.S.

Researchers performed a propensity-matched analysis using electronic data from patients testing positive for SARS-CoV-2 from February 24 to May 13 in a single medical center. “Use of famotidine” was defined as either oral or intravenous famotidine, at any dose, within 7 days of COVID-19 screening and/or hospital admission.

Primary outcomes were in-hospital death, requirement for mechanical ventilation, and a composite of death or requirement for ventilation. Secondary outcomes included serum markers of disease severity.

Of 878 total patients, about 10% received famotidine. Mean age of the whole group was 67, and 55% were men. About 22% of patients died during hospitalization, 27% required mechanical ventilation, and 12% met criteria for “combined death and intubation.”

About two-thirds of patients receiving famotidine received it only as an inpatient, while 29% took the drug prior to admission and received it as an inpatient. Oral famotidine was administered in the large majority of cases versus intravenous famotidine (83% vs 17%, respectively). Patients who received famotidine tended to be younger, but there were no other significant differences in baseline characteristics or pre-existing comorbidities, the authors noted.

Among the matched study group of 772 patients, 51% received hydroxychloroquine, 51% received azithromycin, 49% received corticosteroids, and about 4% received remdesivir.

Use of famotidine was associated with reduced risk of hospital mortality (OR 0.366, 95% CI 0.155-0.862, P=0.021), as well as a lower risk of the combined death or intubation endpoint (OR 0.495, 95% CI 0.228-0.965, P=0.04). https://tpc.googlesyndication.com/safeframe/1-0-37/html/container.html

Intubation occurred in 22% of the famotidine group compared with 32% of the non-famotidine group.

Examining secondary outcomes, use of famotidine was associated with significantly lower median peak C-reactive protein levels and lower median procalcitonin levels. There was also a non-significant trend towards lower median ferritin levels in the famotidine group, the authors noted.

A sensitivity analysis found that the drug seemed to work especially well in patients with the highest national early warning scores (NEWS).

Researchers cautioned that this is a retrospective, observational, single-center study, whose findings should be interpreted with caution. They suggested further research into the effect of famotidine on COVID-19, including dose, route of administration, and timing.

Currently, famotidine is being evaluated in a randomized clinical trial under an investigational new drug waiver in combination with either hydroxychloroquine or remdesivir.

Disclosures

The authors disclosed no conflicts of interest.

Primary Source

American Journal of Gastroenterology



Buzzy anti-aging biotech Unity drops leading program after flop, shares in freefall

Just five months after Biogen’s head of early R&D Anirvan Ghosh left the company to take up the CEO post at Unity Biotechnology, its key leading knee pain program has failed and been thrown onto the trash heap.

The drug, known as UBX0101, had already traveled a rocky path: Last year, Unity posted phase 1 data linking UBX0101 to improved scores on pain symptom questionnaires in patients with moderate to severe osteoarthritis (OA), but the drug failed to statistically outperform placebo in the second part of the study.

Unity, however, plowed on, seeing enough promise in the data to move the p53/MDM2 interaction inhibitor into phase 2. Unity recently completed enrollment in the 183-subject trial, setting it up to post top-line data in the second half of the year.

Now the data are in, but they have proven grim reading: The 12-week results from the phase 2 study in patients with moderate to severe painful OA of the knee found that there “was no statistically significant difference” between any arm of UBX0101 and placebo.

This was based from a baseline in WOMAC-A, an established measurement of pain in OA.

“Given these results, Unity does not anticipate progressing UBX0101 into pivotal studies and will narrow the company’s near-term focus to its ongoing ophthalmologic and neurologic disease programs,” it said in a statement. These are earlier bets, and the setback is a major gut punch for the company.

This will also be a blow for Ghosh, given that it is his first major data readout since becoming chief. “While these are not the results we had hoped for, the evidence that senescent cells contribute to diseases of aging remains compelling, and we are excited to advance UBX1325 for retinal diseases, which inhibits Bcl-xL, a distinct senolytic target,” he said.

Unity works on an anti-aging philosophy based on eradicating accumulated senescent cells, which are a mechanism of aging and a driver of age-associated diseases. The theory is that these therapies can cut out these senescent cells to slow down or even reverse age-associated disease and restore tissue.

These latest data are a setback for the biotech’s theory. Its shares dropped 60% Monday morning on the news.


U.S. states seek $2.2 trillion from OxyContin maker Purdue Pharma

U.S. states claimed they are owed $2.2 trillion to address harm from OxyContin maker Purdue Pharma LP’s alleged role in America’s opioid epidemic, accusing the drugmaker in new filings of pushing prescription painkillers on doctors and patients while playing down the risks of abuse and overdose.

In filings made as part of Purdue’s bankruptcy proceedings that were disclosed on Monday, the states said Purdue, backed by the wealthy Sackler family, contributed to a public health crisis that has claimed the lives of roughly 450,000 people since 1999 and caused strains on healthcare and criminal justice systems. The filings cited more than 200,000 deaths in the U.S. tied directly to prescription opioids between 1999 and 2016.

In large states such as California and New York, claims alone totaled more than $192 billion and $165 billion, respectively. Forty-nine U.S. states, Washington, D.C. and various territories are making the claims. Oklahoma settled litigation with Purdue last year.

Purdue filed for bankruptcy in 2019 under pressure from more than 2,600 lawsuits brought by cities, counties, states, Native American tribes, hospitals and others. The lawsuits said the company, and in some cases the Sacklers, used deceptive marketing and took other improper steps to flood communities with prescription opioids.

The company and family have denied the allegations and pledged to help combat the opioid epidemic, including by providing addiction treatment drugs and overdose reversal medications under development.

In response to the state claims, Purdue said it continues to work toward resolving litigation and emerging from bankruptcy, and that it is typical for claims from various creditors to be “filed in amounts substantially larger than what is ultimately allowed by the court.”

Purdue and the Sacklers have pointed to fentanyl and heroin as more significant culprits in the opioid crisis. States in their filings, though, pointed to National Institute on Drug Abuse research estimating that about 80% of heroin abusers previously took prescription opioids.

In addition to the assertions from states, Purdue faces claims exceeding $18 billion from the U.S. Justice Department on account of potential penalties resulting from criminal and civil investigations.

In filings tied to Purdue’s bankruptcy case, federal prosecutors said Purdue contributed to false claims being made to federal healthcare insurance programs by allowing doctors to write medically unnecessary opioid prescriptions that were at times tainted by illegal kickbacks, according to a person familiar with the matter.

The Justice Department claims also included possible penalties arising from allegations that Purdue violated the U.S. Food, Drug and Cosmetic Act and violations of federal conspiracy and anti-kickback laws, the person said.

The Justice Department has declined to comment on the claims.

Claims from states and federal prosecutors are being processed after being filed just before a July 30 deadline set by a U.S. bankruptcy judge. While they will collectively exceed trillions of dollars, the filings are in many cases placeholders as opposed to roadmaps for how much money Purdue will ultimately pay its creditors, the bulk of which are U.S., state and local governments.

Purdue is only worth a bit more than $2 billion if liquidated. The company values a proposal to settle litigation, which includes providing addiction treatment and overdose-reversing drugs, at more than $10 billion. The Sacklers would contribute $3 billion and cede control of Purdue, with the company becoming a trust run on behalf of plaintiffs.


Those financial realities underscore that Purdue does not have enough money to satisfy the myriad claims against it.

States and other litigants are in talks to determine how to allocate proceeds from Purdue’s bankruptcy estate as part of the company’s attempted reorganization. Many states, including Massachusetts, New York and Connecticut, have opposed Purdue’s settlement offer, insisting the Sacklers contribute more money and reveal more details about their finances.


Iowa COVID-19 system glitch wrongly lowered confirmed case rate

A glitch in Iowa’s COVID-19 website artificially lowered the number of confirmed cases, according to an ABC News report

Four things to know:

1. The glitch led to the Iowa health department reporting fewer new infections and smaller COVID-19 daily positive test percentage than there actually were. Dana Jones, DNP, a nurse practitioner in Iowa City, identified the issue.

2. Due to the glitch, potentially thousands of COVID-19 positive tests were wrongly recorded as having been taken between March and June.

3. In some cases, people tested negative earlier in the year but then positive on a second test taken more recently; Iowa’s system recorded their new positive results as having happened on the date of their first test.

4. The Iowa health department acknowledged the glitch and is working to correct it.

“It’s just horrifying,” said Dr. Jones. “We have no idea what’s going on, really. I don’t know how much this changes the positivity rate but it is lower on the site than it truly is in reality.”