Builds on existing collaboration with Novartis for pelacarsen, which is currently being evaluated in a Phase 3 cardiovascular outcome study with data expected in 2025
Ionis' new and advanced technologies will be used to create next generation compound targeting Lp(a)
Ionis will receive a $60 million upfront payment
- Announced consistently positive results from the Phase 3 ATTRibute-CM study of acoramidis in patients with transthyretin amyloid cardiomyopathy (ATTR-CM), including a highly statistically significant result observed on the primary endpoint with a Win Ratio of 1.8 (p<0.0001) and clinically meaningful and consistent separation observed on measures of mortality, morbidity, function, and quality of life; the Company intends to file a New Drug Application (NDA) for acoramidis with the U.S. Food and Drug Administration (FDA) by the end of 2023
- Presented updated six-month results from Cohort 5 of PROPEL2, a Phase 2 trial of infigratinib in children with achondroplasia, at the Endocrine Society 2023 Annual Conference (ENDO 2023), demonstrating a continued potentially best-in-class efficacy and well-tolerated safety profile, and a mean increase in annualized height velocity (AHV) of 3.38cm/year with no treatment-related adverse events
- Dosed the first participant in FORTIFY, a global Phase 3 study of BBP-418 in patients with limb girdle muscular dystrophy type 2I/R9 (LGMD2I/R9) and met with the FDA to discuss the use of glycosylated alpha-dystroglycan (αDG) levels as a surrogate endpoint; based on this meeting, the Company believes there is potential to pursue Accelerated Approval in the U.S. for BBP-418
- Shared 18-month data from the long-term extension of the Phase 2 study of encaleret in patients with autosomal dominant hypocalcemia type 1 (ADH1) at ENDO 2023, including observation of a rapid and sustained treatment effect; Phase 3 CALIBRATE registrational trial remains ongoing, with topline results expected to be announced in the first half of 2024
- Phase 1/2 trial of BBP-631 for treatment of congenital adrenal hyperplasia (CAH) continuing to progress with an update planned by the end of 2023
- Three lead KRAS programs are advancing, with an Investigational New Drug (IND) application planned for first-in-class direct KRASG12C (ON) inhibitor BBO-8520 in 2023 as well as a recent selection of a clinical candidate for PI3Kα:RAS breaker with the intention to file an IND application in 2024
- Ended the quarter with $353 million in cash, cash equivalents, marketable securities, and short-term restricted cash, and $50 million of investments in equity securities, providing runway into 2H 2024
Q2 2023 total revenues increased to $110.8 million, compared to $55.6 million in the same period in 2022
CAPLYTA Q2 2023 net product sales were $110.1 million, compared to $55.1 million for the same period in 2022, representing a 100% increase
CAPLYTA’s strong prescription uptake continues: Q2 2023 CAPLYTA total prescriptions increased 96%, versus the same period in 2022 and 13% sequentially versus Q1 2023
2023 CAPLYTA net product sales guidance raised to $445 - $465 million
Company continued to see rapid progression and acceleration of enrollment with 180 patients enrolled to date across 46 clinical trial sites, globally
Completion of enrollment of study expected by end of 2023
Company has documented the necessary number of patients reaching the primary efficacy endpoint (overall survival) to conduct pre-planned interim analysis
Topline data from interim analysis expected before year end
https://finance.yahoo.com/news/cns-pharmaceuticals-provides-clinical-trial-120000035.html
Achieved Second Quarter 2023 Global Net Product Revenues of $306 Million, Representing 43% Year-Over-Year Growth Compared to Q2 2022 –
−Submitted 18-Month APOLLO-B Data to the U.S. Food and Drug Administration as Amendment to Supplemental New Drug Application for Patisiran –
−Presented Updated Positive Interim Results from Phase 1 Study of ALN-APP in Patients with Early-Onset Alzheimer’s Disease –
−Entered into Global Strategic Collaboration with Roche for Co-Development and Co-Commercialization of Zilebesiran –
−U.S. Attorney’s Office for District of Massachusetts Concluded and Closed Investigation Regarding Marketing and Promotion of ONPATTRO, with no Action Taken –
−Akshay Vaishnaw, M.D., Ph.D., Named Alnylam’s First Chief Innovation Officer –
− Reiterated 2023 Financial Guidance, Including Combined Net Product Revenues of $1,200 Million to $1,285 Million –
About 200,000 people leave military service each year in the U.S. and transition to civilian life. By the government’s own account, this change can be very challenging. One career option for those leaving the military is in biopharma, and for those considering this route, programs exist specifically to help them find a path.
“It’s often challenging for many individuals who are transitioning out of military service to understand what’s going to be the best fit for them,” Derek Heim, who leads Merck’s Veterans Leadership Network, told BioSpace. In this regard, he noted that Merck’s mission to save and improve lives can be very meaningful for them. “A lot of veterans will look for a mission-focused company to work for.”
The Veterans Leadership Network is a global group of nearly 1,500 veterans, military family members and their supporters within Merck. While the program in its current form began in 2009, Heim said the company’s efforts to recruit veterans stretches back much longer, and furthers Merck’s aim of having its workforce reflect the diversity of its patients around the world.
In addition, those who’ve served in the U.S. military tend to have a solid foundation in “strategic thinking, critical thinking as it impacts the international space, the political aspects of working in different countries,” he said. “There’s a distinct execution of project management, execution of strategy and realization that the military is really exceptionally trained in—they do this 24/7 during their careers.”
One way Merck recruits veterans is by participating in the Department of Defense’s SkillBridge program, which allows servicemembers to gain civilian work experience during their final months in the military. Heim said the company has also worked to identify job requisitions for which years in military service could be substituted for years of experience in the pharmaceutical industry and has revised the requisitions to reflect this.
The company also helps highly talented service members build their resumes and identify roles within the company that could be a fit. Once hired, service members in the Veterans Leadership Network are assigned a mentor to help them learn about the company.
Merck is not alone in its efforts to help servicemembers transition into the biopharma industry. Amgen, AstraZeneca, Pfizer and Roche are among the other companies that tout their efforts to recruit and retain veterans.
In addition to SkillsBridge, there are other U.S. government programs that aim to facilitate the transition to civilian careers, including those in biopharma. In North Carolina, the state-funded NCBiotech places veterans in internships as a stepping stone to careers in the industry. And some occupations in the Army, Navy and Air Force are directly related to roles in biopharma, a Department of Labor spokesperson noted in an email to BioSpace. These include laboratory technician, pharmacy specialist and medical supply-related roles.
As for the roles veterans take on within the industry, Heim said that in the past, manufacturing tended to be seen as the clearest fit at Merck for former servicemembers’ skill sets. The company is now moving toward taking a broader view at how veterans can contribute, he said.
“Thinking through what the mission is that we're trying to accomplish, and being able to construct that narrative and communicate it clearly and concisely in big matrix organizations—you can see a need for that across all of our departments within the company.”
The powerhouse of weight loss and type 2 diabetes drugs, glucagon-like peptide-1 receptor agonists, have also shown the potential to treat nonalcoholic fatty liver disease, cardiovascular disease and Alzheimer’s disease—and early research suggests they could treat addiction too.
Glucagon-like peptide-1 (GLP-1) is a hormone that stimulates insulin secretion after eating, enabling a feeling of fullness and regulating blood sugar. GLP-1 agonists mimic the effects of this hormone, making them an effective treatment for diabetes and obesity.
Now, anecdotal reports suggest the mechanism may work in addictive disorders as well. Michael Glickman, an obesity medicine specialist at Revolution Medicine, Health & Fitness, told BioSpace he has had many patients report less desire to drink or smoke after starting such treatments.
Drug consumption is partly driven by the pharmacological effects that trigger reward circuits in the brain, according to a review published in 2019 in Physiological Reviews. These effects mostly depend on dopamine signaling in the nucleus accumbens, the authors write.
Preclinical studies have shown that GLP-1 agonists can circumvent the release of dopamine in this primary reward center, Patricia “Sue” Grigson, an addiction researcher at Pennsylvania State University, told BioSpace.
Glickman agreed, saying the patient reports suggest that GLP-1 is “blunting that pleasure response across the board. I think there are so many interplays in the brain that are involved with the dopamine pleasure response, and addiction falls into that.”
The other way targeting the GLP-1 receptor may work, Grigson said, is by reducing someone’s responsiveness to “cues” for a drug. There are three roads to relapse, she said. “One is being re-exposed to cues in contexts that are associated with the drug. The second is being re-exposed to the drug after a period of abstinence, and the other is stress.”
GLP-1 and its receptor are particularly engaged in people who both drink and eat a lot, Lorenzo Leggio, a physician-scientist at the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and the National Institute on Drug Abuse (NIDA), told BioSpace.
“There is an important overlap in the body between the mechanism that regulates pathological overeating and the mechanism that regulates pathological overdrinking,” he said. “The idea is that in order for [a drug targeting GLP-1 to work], you need to have an imbalance in the pathological GLP-1 system, and by giving GLP-1 . . . you are fixing that impairment.”
Leggio’s team is exploring this hypothesis in a number of studies, including one where they measured GLP-1 levels in the blood of alcohol use disorder (AUD) patients.
“What we saw was that . . . after drinking alcohol, GLP-1 was going down,” Leggio told BioSpace. While GLP-1 levels rise with food consumption to regulate glucose, Leggio said that alcohol may work along the same pathway but have the opposite effect.
Leggio recently published another paper in JCI Insight showing that semaglutide, the key ingredient in Novo Nordisk’s GLP-1 receptor agonists Wegovy, Ozempic and Rybelsus, reduces alcohol consumption and binge-like drinking in rodents. Leggio said this preclinical evidence shows semaglutide “may be a promising new medication for [AUD].”
He said that from a pure, neurobiological standpoint, there is a strong consensus that GLP-1 plays an important role in AUD. What is not known, he cautioned, is whether the preclinical findings will translate to humans.
Recent evidence suggests it might. In 2022, Mette Kruse Klausen of the Psychiatric Centre Copenhagen and colleagues published a study of 127 people with AUD randomized to receive either AstraZeneca’s GLP-1 receptor agonist exenatide or a placebo once a week for 26 weeks, in addition to standard cognitive-behavioral therapy.
While exenatide did not significantly reduce the number of heavy drinking days compared with placebo, the authors reported that it did reduce alcohol cue reactivity in the ventral striatum and septal area—also key reward centers in the brain. Interestingly, exploratory analyses showed that exenatide did significantly reduce heavy drinking days and total alcohol intake in a subgroup of obese patients.
Leggio is also pursuing this question, with plans to study semaglutide in people with AUD. The study is currently under review by the Institutional Review Boards (IRB), and Leggio said he expects the outcome “very soon.”
NIAAA is also collaborating with the University of North Carolina at Chapel Hill on a Phase II trial studying the use of semaglutide in smokers with AUD. Preclinical evidence indicates that GLP-1 “impacts both alcohol and nicotine motivation and intake,” according to the study outline, published on ClinicalTrials.gov.
And at Penn State, Grigson’s team is conducting a study assessing another GLP-1 analog, liraglutide, as a treatment for opioid use disorder in patients at the Caron Treatment Centers. She expects initial data this October.
Grigson’s lab takes the position that addiction involves having a “real physiological need for the drug.” So, her team is also exploring whether GLP-1 drugs might reduce the experience of withdrawal when someone abruptly stops using a substance to which their system is accustomed. In a soon-to-be-published preclinical study, the researchers were able to block evidence of conditioned withdrawal using a GLP-1 agonist. “GLP-1 agonists might be working there in order to reduce that heavy physiological need,” Grigson said.
Leggio called it a “very, very exciting time” for the space because “several clinical investigators are jumping to this very promising target and running studies.”
Not all research on GLP-1 agonists for addiction has been positive, however. A study published in 2021 found that low-dose exenatide did not alter cocaine self-administration in people with cocaine use disorder (CUD). However, the authors stated that they were unable to draw firm conclusions as to exenatide’s efficacy in CUD as the drug was only given once rather than as chronic pre-treatment.
Grigson agreed that the single dose could have contributed to the result and added that the study participants didn’t have a desire to quit taking cocaine. In Grigson’s experience, there is also a notable difference in the effect of GLP-1 drugs on people seeking out a drug and taking it when it is placed in front of them. “The effects on taking are smaller than the effects on seeking,” she said. “The seeking is where you get the big effect.”
Grigson cautioned that GLP-1 drugs will not work for everyone. “No drug is going to be a panacea,” she said. “But it’s one more tool in our toolbox; one more opportunity to provide treatment for some people.”
https://www.biospace.com/article/glp-1-drugs-show-promise-in-alcohol-opioid-use-disorders-/
