Lilly breaks new ground for BTK class with Jaypirca approval

 Eli Lilly has picked up an FDA approval for its non-covalent BTK inhibitor Jaypirca in relapsed mantle cell lymphoma (MCL) patients who relapse after treatment with current drugs in the class.

The accelerated approval covers adults MCL patients who have previously been treated with at least two lines of systemic therapy, including a covalent BTK inhibitor.

Jaypirca (pirtobrutinib) has been specifically designed to work in patients who develop resistance mutations to current BTK inhibitors for MCL, such as AbbVie/Johnson & Johnson’s Imbruvica (ibrutinib), AstraZeneca’s Calquence (acalabrutinib), and BeiGene’s Brukinsa (zanubrutinib).

It is the first non-covalent or reversible BTK drug to be cleared by the FDA, and targets a different binding site on the BTK protein for its mechanism of action.

In the open-label, phase 1/2 BRUIN clinical trial, which included 120 patients with MCL as well as patients with other forms of blood cancer, Jaypirca at an oral dose of 200 mg once a day had an objective response rate of 50%, including 13% complete responses, and median duration of response of more than eight months.

Patients in the study had been treated with a median of three prior lines of therapy, including at least one covalent BTK inhibitor.

“Until now, people living with MCL who can no longer be treated with BTK inhibitors have had few alternatives,” commented Meghan Gutierrez, chief executive of the Lymphoma Research Foundation in the US.

“The approval of Jaypirca brings a new treatment option and, along with that, new hope for people with relapsed or refractory MCL,” she added.

MCL is pretty rare, but this first FDA approval raises expectations that Lilly could also get a green light for Jaypirca in other indications like chronic lymphoblastic leukaemia (CLL) and small lymphocytic leukaemia (CLL), which cover a much larger patient population.

At last year’s ASH congress, results from the CLL cohort in BRUIN showed that Jaypirca achieved a stellar ORR of more than 82% in patients previously treated with a BTK drug, and 79% in patients previously-treated with Abbvie’s BCL-2 inhibitor Venclexta (venetoclax), another important therapy for MCL.

Continued approval in MCL meanwhile is likely to depend on the outcome of confirmatory clinical trials. Lilly is running a phase 3 trial called BRUIN MCL-321, which is comparing Jaypirca to physician’s choice of BTK inhibitors in MCL patients who have received one or more prior lines of therapy and are BTK inhibitor naïve.

Jaypirca is expected to be available in the US “in the coming weeks,” said Lilly, which has set a list price of $21,000 for a 30-day supply of the drug, a premium to the covalent BTK drugs which typically cost between $13,000 and $16,000 per month.

https://pharmaphorum.com/news/lilly-breaks-new-ground-for-btk-class-with-jaypirca-approval/

EMA reviewing Novartis’ Adakveo after phase 3 miss

 The EMA’s human medicines committee has started a review of Novartis’ sickle cell disease (SCD) therapy Adakveo, shortly after the company reported that it failed to show efficacy in a phase 3 trial.

On Friday, Novartis said that the phase 3 STAND trial of Adakveo (crizanlizumab) found no statistically significant difference between the drug and placebo on annualised rates of vaso-occlusive crises (VOCs) – the excruciatingly painful attacks that intermittently affect patients with SCD.

The EU regulator’s Committee for Medicinal Products for Human Use (CHMP) said it will “assess the impact of these findings on the balance of benefits and risks of Adakveo” and the impact on its conditional approval, which was granted in 2020.

STAND found no benefit over placebo on VOC rates for both doses of Adakveo on test – 5 mg/kg and 7.5 mg/kg given as a 30-minute infusion once a month – which Novartis said was “inconsistent with previous trial results” with the drug.

Anti-P-selectin antibody Adakveo became the first new treatment for VOCs in SCD patients in decades when it was approved for marketing in the EU, a few months after the FDA gave it the nod in the US, on the strength of the SUSTAIN trial results.

That study showed that Adakveo lowered the median annual rate of VOCs to 1.63 compared to 2.98 for placebo, which is equivalent to a 45% reduction, regardless of sickle cell disease genotype or whether they were receiving hydroxyurea, a decades-old treatment for SCD.

It also found that the number of days patients stayed in hospital was reduced 42% with Adakveo, with 36% of those taking the drug experiencing no VOCs versus 17% of placebo-treated patients.

“In order to determine the appropriate next steps, Novartis is working with regulators globally, including the EMA, which requested data from STAND as part of the conditions for marketing authorisation, as well as with the FDA and trial investigators,” said the company in a statement.

The review and failed trial comes as competition to Adakveo is already coming under competitive pressure from Pfizer’s Oxbryta (voxelotor), acquired as part of its $5.4 billion takeover of SCD specialist Global Blood Therapeutics (GBT) which closed last October.

That deal also gave Pfizer rights to GBT’s inclacumab – also a P-selectin antibody – that is claimed to have greater potency and could potentially only need to be dosed once every three months. Pfizer has previously said it believes that GBT’s pipeline – which includes an Oxbryta follow-up codenamed GBT601 – could generate more than $3 billion in peak annual sales.

https://pharmaphorum.com/news/ema-reviewing-novartis-adakveo-after-phase-3-miss/

Evolus: "Extra-Strength" Jeuveau® Demonstrates Effects Lasting 26 Weeks in Interim Phase II

 

• “Extra-strength” 40U formulation achieves one-point improvement on the Glabellar Lines Scale with the duration of effect lasting 26 weeks, representing a prolonged 6-month performance
• Results indicate a favorable safety profile; no serious adverse events reported and 88% of all adverse events were mild
• Potential new “extra-strength” formulation would expand Evolus' Jeuveau^® offering
• Trial completion expected mid-2023; final results anticipated to be presented in 2H 2023

https://www.biospace.com/article/releases/-extra-strength-formulation-of-jeuveau-demonstrates-effects-lasting-26-weeks-in-interim-phase-ii-data-results-representing-prolonged-6-month-performance/

Japan gives priority review status to Alzheimer's drug developed by Eisai, Biogen

 Japanese drugmaker Eisai Co Ltd and U.S. biotech firm Biogen Inc said in a joint statement that the Japanese Ministry of Health, Labour and Welfare has granted priority review status to their Alzheimer's disease treatment.

The drug, lecanemab, which was recently granted accelerated approval in the United States, is an antibody that has been shown to remove sticky deposits of a protein called amyloid beta from the brains of patients in the early stages of the mind-wasting disease.

In their Jan. 29 statement, the companies said priority review in Japan is granted to new medicines recognised as having high medical utility for serious diseases. Once the priority status has been granted, the target total review period is shortened, they said.

The pair's application for priority status was based on results from a late-stage study in which the drug was shown to reduce the rate of cognitive decline in patients with early Alzheimer's by 27%, compared with a placebo.

Nearly all previous experimental drugs using the same approach have failed.

Earlier this month, Eisai also applied for full approval of the drug with the U.S. Food and Drug Administration (FDA) as a treatment for patients in the earliest stages of the neurodegenerative disease.

https://www.yahoo.com/now/japan-grants-priority-review-status-235230612.html

Sanofi and Regeneron's Dupixent wins new European Commission approval

  Healthcare companies Sanofi and Regeneron said on Monday that their Dupixent product had won approval from the European Commission to treat eosinophilic esophagitis (EoE), which is a condition that damages the esophagus.

"This latest approval establishes Dupixent as the only targeted medicine specifically indicated for eosinophilic esophagitis in the European Union," said George D. Yancopoulos, President and Chief Scientific Officer at Regeneron.

https://finance.yahoo.com/news/sanofi-regenerons-dupixent-wins-european-060856511.html

Hong Kong to ban CBD, label it a ‘dangerous drug’

 Hong Kong will ban CBD starting Wednesday, categorizing it as a “dangerous drug” and mandating harsh penalties for its smuggling, production and possession, customs authorities announced Friday.

Supporters say CBD can treat a range of ailments including anxiety and that, unlike its more famous cousin THC — which is already illegal in Hong Kong — CBD doesn’t get users high. Cannabidiol, derived from the cannabis plant, was previously legal in Hong Kong, where bars and shops sold products containing it.

But Hong Kong authorities decided last year to prohibit the marijuana-derived substance — a change that will soon go into effect. Residents were given three months from Oct. 27 to dispose of their CBD products in special boxes set up around the city.

“Starting from February 1, cannabidiol, aka CBD, will be regarded as a dangerous drug and will be supervised and managed by the Dangerous Drugs Ordinance,” customs intelligence officer Au-Yeung Ka-lun said at a news briefing.

“As of then, transporting CBD for sale, including import and export, as well as producing, possessing and consuming CBD, will be illegal,” Au-Yeung said.

Penalties include up to life in prison and Hong Kong $5 million ($638,000) in fines for importing, exporting or producing CBD. Possession of the substance can result in a sentence of up to seven years and Hong Kong $1 million ($128,000) in fines.

In announcing the ban last year, the Hong Kong government cited the difficulty of isolating pure CBD from cannabis, the possibility of contamination with THC during the production process and the relative ease by which CBD can be converted to THC.

“We will tackle all kinds of dangerous drugs from all angles and all ends, and the intelligence-led enforcement action is our major goal,” Chan Kai-ho, a divisional commander with the department’s Airport Command, told reporters Friday.

Despite the harsh penalties mandated, Chan said authorities would handle enforcement on a case-by-case basis and “seek legal advice from our Department of Justice to determine what the further actions will be.”

Hong Kong maintains several categories of “dangerous drugs,” which include “hard drugs” such as heroin and cocaine, as well as marijuana.

Hong Kong’s first CBD cafe opened in 2020 and the ban will force scores of businesses to remove CBD-infused gummies, drinks and other products, or shut down altogether.

The ban is in keeping with a zero-tolerance policy toward drugs in Hong Kong, a semi-autonomous southern Chinese business hub, as well as on mainland China, where CBD was banned in 2022.

Chinese authorities have waged battles against heroin and methamphetamines, particularly in the southwest bordering on the drug-producing Golden Triangle region spanning parts of Myanmar, Thailand and Laos.

Criminal penalties for both sale and usage are also enforced for marijuana. In one of the most high-profile cases, Jaycee Chan, the son of Hong Kong action star Jackie Chan, served a six month sentence in 2014-2015 for allowing people to consume marijuana in his Beijing apartment amid a crackdown on illegal narcotics in the Chinese capital.

At the same time, China has been a main source of the precursor chemicals used to manufacture the dangerous drug fentanyl, a trade often facilitated through social media.

A wealthy Asian financial center with a thriving commercial port and major international airport, Hong Kong is a key point of entry to China as well as a market for some drugs, especially cocaine. Police have recently seized hundreds of kilograms (pounds) of the drug worth tens of millions of dollars, some of it hidden in a shipment of chicken feet from Brazil.

Most Asian nations maintain strict drug laws and enforce harsh penalties for violators, including the death penalty, with the exception of Thailand, which made it legal to cultivate and possess marijuana last year.

Debate over CBD policy continues in many countries and regions.

The U.S. Food and Drug Administration said Thursday there’s not enough evidence about CBD to confirm that it’s safe for consumption in foods or as a dietary supplement. It called on Congress to create new rules for the massive and growing market.

Marijuana-derived products have become increasingly popular in lotions, tinctures and foods, while their legal status has been murky in the U.S., where several states have legalized or decriminalized substances that remain illegal federally.

https://apnews.com/article/health-china-government-hong-kong-marijuana-a250ce49735c1b6e67b78895bad60bab

Nuclear strike chief seeks cancer review of missile crews

 The top Air Force general in charge of the nation’s air- and ground-launched nuclear missiles has requested an official investigation into the number of airmen who are reporting blood cancer diagnoses after serving at Malmstrom Air Force Base in Montana.

The illnesses became publicly known this week after The Associated Press obtained a military brief that at least nine missileers — those officers serving in underground bunkers near silo-based Minuteman III intercontinental ballistic missiles and responsible for turning launch keys if ordered — were reporting diagnoses of non-Hodgkin lymphoma. One of the officers has died.

Gen. Thomas A. Bussiere, commander of Air Force Global Strike Command, which is responsible for all of the silo-based and aircraft-launched nuclear warheads, said in a statement to the AP Friday that he has requested that the U.S. Air Force School of Aerospace Medicine conduct a formal assessment into the reported cancers.

“Air Force Global Strike Command and our Air Force takes the responsibility to protect airmen and Guardians incredibly seriously, and their safety and health is always my top priority,” Bussiere said. “While we continue to work through this process, service members and their dependents as well as former service members who may have concerns or have questions are encouraged to speak with their healthcare providers.”

Air Force spokeswoman Ann Stefanek added in a statement Saturday that the review will go beyond the launch officers initially identified.

Similar nuclear missile facilities are located at Minot Air Force Base in North Dakota and F.E. Warren Air Force Base in Wyoming.

“Gen. Bussiere asked for an assessment of the risks to all airmen and Guardians involved with the missile community who may be at risk,” Stefanek said.

The Air Force told the AP on Jan. 22 that its medical teams were looking into the issue. Bussiere’s request elevates that into a formal review conducted by the U.S. Air Force School of Aerospace Medicine.

“We are working together to create courses of action moving forward. We are committed to remaining transparent during this process and we pledge to maintain an open dialogue with members, their families and stakeholders throughout,” Bussiere said.

Over the past week, more missileers who served at Malmstrom or their families have reached out to the AP to share their experiences with diagnoses of blood cancer and other types of cancer.

Concern about the cancers was raised by a Space Force officer in a January briefing to his unit. Many missileers transferred into the Space Force after it was created; at least 455 Space Force officers, including its highest-ranking officer, new Chief of Space Operations Gen. Chance Saltzman, served as missileers.

Non-Hodgkin lymphoma, which according to the American Cancer Society affects an estimated 19 out of every 100,000 people in the U.S. annually, is a blood cancer that uses the body’s infection-fighting lymph system to spread.

For comparison, only about 3,300 troops are based at Malmstrom at a time, and only about 400 of those are assigned either as missileers or as support for those operators. The three bases control a total of 400 siloed Minuteman III ICBMs.

https://apnews.com/article/politics-health-lymphoma-montana-b6b4de97d7b77a89541e2df8a1d60880