Pfizer made 6 mln courses of COVID pill, hitting Q1 target

 Pfizer Inc said on Monday it made 6 million courses of its antiviral COVID-19 pill Paxlovid in the first quarter, hitting a target set by Chief Executive Albert Bourla.

Pfizer spokesperson Sharon Castillo said in an email that the company has shipped the pills to over 26 countries so far.

Bourla has said the company expects to produce at least 120 million courses of the drug this year, with 30 million of those courses coming in the first half.

The U.S. government has bought 20 million of those courses, with the first 10 million expected to be delivered by the end of June. Around 1.4 million courses have been distributed in the United States so far.

Paxlovid is expected to be an important tool in the fight against COVID-19 after it reduced hospitalizations in high-risk patients by around 90% in a clinical trial. The results were significantly better than those for Merck & Co's rival antiviral pill molnupiravir in its clinical trial.

https://www.marketscreener.com/news/latest/Pfizer-made-6-mln-courses-of-COVID-pill-hitting-Q1-target--39962905/

Experimental ‘gene silencing’ therapy reduces lipoprotein(a), risk factor of heart disease, up to 98%

 Findings from a new Cleveland Clinic-led phase 1 trial show that an experimental "gene silencing" therapy reduced blood levels of lipoprotein(a), a key driver of heart disease risk, by up to 98%.

Findings from the "APOLLO Trial: Magnitude and Duration of Effects of a Short-interfering RNA Targeting Lipoprotein(a): A Placebo-controlled Double-blind Dose-ranging Trial" were presented today during a late-breaking science session at the American College of Cardiology's 71st Annual Scientific Session and simultaneously published online in the Journal of the American Medical Association.

In the trial, participants who received higher doses of SLN360 -- a small interfering RNA (siRNA) therapeutic that "silences" the gene responsible for lipoprotein(a) production -- saw their lipoprotein(a) levels drop by as much as 96%-98%. Five months later, these participants' lipoprotein(a) -- also known as Lp(a) -- levels remained 71%-81% lower than baseline.

The findings suggest this siRNA therapy could be a promising treatment to help prevent premature heart disease in people with high levels of Lp(a), which is estimated to affect 64 million people in the United States and 1.4 billion people worldwide. It is estimated that nearly 20 to 25% of the world's population has elevated Lp(a).

"These results showed the safety and strong efficacy of this experimental treatment at reducing levels of Lp(a), a common, but previously untreatable, genetically-determined risk factor that leads to premature heart attack, stroke and aortic stenosis," said the study's lead author Steven E. Nissen, M.D., Chief Academic Officer of the Heart, Vascular & Thoracic Institute at Cleveland Clinic. "We hope that further development of this therapy also will be shown to reduce the consequences of Lp(a) in the clinical setting through future studies."

Lp(a) has similarities to LDL, also known as bad cholesterol. Lp(a) is made in the liver, where an extra protein called apolipoprotein(a) is attached to an LDL-like particle. Unlike other types of cholesterol particles, Lp(a) levels are 80 to 90% genetically determined. The structure of the Lp(a) particle causes the accumulation of plaques in arteries, which play a significant role in heart disease. Elevated Lp(a) greatly increases the risk of heart attacks and strokes.

Although effective therapies to reduce the risk of heart disease by lowering LDL cholesterol and other lipids exist, currently there are no approved treatments to lower Lp(a). Since Lp(a) levels are determined by a person's genes, lifestyle changes such as diet or exercise have no effect. In the current study, the siRNA therapy reduces Lp(a) levels by "silencing" the gene responsible for Lp(a) production and blocking creation of apolipoprotein(a) in the liver.

In the APOLLO trial, researchers enrolled 32 people at five medical centers in three countries. All participants had Lp(a) levels above 150 nmol/L, with a median level of 224 nmol/L (75 nmol/L or less is considered normal). Eight participants received a placebo and the remaining received one of four doses of SLN360 via a single subcutaneous injection. The doses were 30 mg, 100 mg, 300 mg and 600 mg. Participants were closely observed for the first 24 hours after their injection and then assessed periodically for five months.

Participants receiving 300 mg and 600 mg of SLN360 had a maximum of 96% and 98% reduction in Lp(a) levels, and a reduction of 71% and 81% at five months compared to baseline. Those receiving a placebo saw no change in Lp(a) levels. The highest doses also reduced LDL cholesterol by about 20%-25%. There were no major safety consequences reported and the most common side effect was temporary soreness at the injection site. The study was extended and researchers will continue to follow participants for a total of one year.

The APOLLO trial was funded by Silence Therapeutics plc (Nasdaq: SLN), London, UK. Dr. Nissen has served as a consultant for many pharmaceutical companies and has overseen clinical trials for Amgen, AstraZeneca, Bristol Myers Squibb, Eli Lilly, Esperion, Novartis, Novo Nordisk, Orexigen, Takeda and Pfizer. However, he does not accept honoraria, consulting fees or other compensation from commercial entities.

The trial was coordinated by the Cleveland Clinic Coordinating Center for Clinical Research (C5Research) and sponsored by Silence Therapeutics plc (Nasdaq: SLN), London, UK.

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Story Source:

Materials provided by Cleveland Clinic. Note: Content may be edited for style and length.

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Journal Reference:

1. Steven E. Nissen, Kathy Wolski, Craig Balog, Daniel I. Swerdlow, Alison C. Scrimgeour, Curtis Rambaran, Rosamund J. Wilson, Malcom Boyce, Kausik K. Ray, Leslie Cho, Gerald F. Watts, Michael Koren, Traci Turner, Erik S. Stroes, Carrie Melgaard, Giles V. Campion. Single Ascending Dose Study of a Short Interfering RNA Targeting Lipoprotein(a) Production in Individuals With Elevated Plasma Lipoprotein(a) Levels. JAMA, 2022; DOI: 10.1001/jama.2022.5050

https://www.sciencedaily.com/releases/2022/04/220403121140.htm

Cause of metastasis in prostate cancer discovered

 Prostate cancers remain localised in the majority of cases, giving affected individuals a good chance of survival. However, about 20% of patients develop incurable metastatic prostate cancer, resulting in approximately 5,000 deaths each year in Austria alone. Medical research has not yet adequately explained why metastases occur in some people and not in others. A research team at MedUni Vienna has now discovered specific changes in a protein that drive the growth and spread of prostate cancer. The study was recently published in the journal Molecular Cancer.

In the study, the researchers broke new ground and investigated the role of the protein KMT2C in prostate cancer. KMT2C is a genetic component that essentially functions as a regulator of central cellular processes. If KMT2C loses this regulatory ability due to typical cancer-related mutations, this encourages the proliferation of the cancer gene MYC. This in turn causes cells to divide at an increased rate, driving both growth and spread of the cancer.

New insights into the transition to metastasis

"Our study provides new insights into the previously poorly understood transition from localised prostate cancer to terminal metastatic prostate cancer," says study leader Lukas Kenner (Department of Pathology at MedUni Vienna, Comprehensive Cancer Center of MedUni Vienna and University Hospital Vienna, Department of Laboratory Animal Pathology at Vetmeduni Vienna and the K1 Center CBmed), underlining the significance of the research work. In addition, the knowledge gained about the effects of KMT2C mutations may also generate new momentum for the diagnosis and treatment of prostate cancer.

Diagnosing aggressive progression at an early stage

KMT2C mutation status can be measured via a blood test, allowing early diagnosis of potentially aggressive progression in prostate cancers. In addition, MYC inhibitors could be used to prevent increased cell division, and hence metastasis, and it is hoped that further scientific studies will substantiate this. MYC inhibitors are essentially new cancer treatment drugs that have already been tested in clinical trials and -- if further studies confirm this -- could also be used in metastatic prostate cancer in the next few years. "Since a high level of KMT2C mutation characterises many types of cancer, such as breast, lung, colorectal, bladder and even skin cancer, our study results have a great deal of potential in the research, diagnosis and treatment of malignant cancers in general," says Lukas Kenner.

Story Source:

Materials provided by Medical University of Vienna. Note: Content may be edited for style and length.

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Journal Reference:

1. Tanja Limberger, Michaela Schlederer, Karolina Trachtová, Ines Garces de los Fayos Alonso, Jiaye Yang, Sandra Högler, Christina Sternberg, Vojtech Bystry, Jan Oppelt, Boris Tichý, Margit Schmeidl, Petra Kodajova, Anton Jäger, Heidi A. Neubauer, Monika Oberhuber, Belinda S. Schmalzbauer, Sarka Pospisilova, Helmut Dolznig, Wolfgang Wadsak, Zoran Culig, Suzanne D. Turner, Gerda Egger, Sabine Lagger, Lukas Kenner. KMT2C methyltransferase domain regulated INK4A expression suppresses prostate cancer metastasis. Molecular Cancer, 2022; 21 (1) DOI: 10.1186/s12943-022-01542-8

https://www.sciencedaily.com/releases/2022/04/220404105723.htm

Florida lawmaker vows to make gender-affirming care for minors felony child abuse

 

• A Florida lawmaker on Monday promised to introduce legislation next session to criminalize gender-affirming care for minors should he be reelected in November.

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• Randy Fine, a Republican and member of the state House of Representatives, said Monday that women’s sports had become a “joke” and schools a “cesspool” because of transgender women and girls.

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• Fine’s statement comes just a week after Florida’s controversial “Don’t Say Gay” bill was signed into law.

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A Florida Republican on Monday pledged to introduce legislation next session that would make providing gender-affirming services to minors illegal.

Randy Fine, a member of the state House of Representatives, on Monday said he would “shepard legislation” next session to make providing gender-affirming care to minors, including medications and surgeries, felony child abuse, punishable by prison time or the revocation of a medical license.

“If an adult wants to self-mutilate in pursuit of the fiction they can defy G-d and science, more power to them — as they don’t expect me to pay for it,” Fine tweeted Monday. “But no child should be put in the position of making life-altering decisions before they are of the age of majority.”

Florida is just shy of a year out from its 2023 session and Fine, who has served in the state House of Representatives since 2016, is up for reelection in November.

Fine has been a vocal critic of transgender people and last year was one of more than 70 Republicans in the House to vote in favor of a bill prohibiting transgender women and girls from playing on sports teams consistent with their gender identity, though that legislation later died in the state Senate.

“I can say I’m a porcupine, but that doesn’t make it so,” Fine tweeted on Monday. “It is time to dispense with this fantasy making women’s sports a joke and our schools into a cesspool.”

“I’ve taken on Common Core, university corruption, and school board lawbreaking,” Fine added. “And won every time. This is next.”

Fine’s comments come exactly a week after Florida Gov. Ron DeSantis (R) signed into law House Bill 1557– known to its critics as the “Don’t Say Gay” bill – which bars primary school teachers from engaging in classroom instruction related to sexual orientation and gender identity. Florida public school teachers of all grade levels will be prohibited from addressing those topics in a manner that is not “age appropriate or developmentally appropriate” for their students.

DeSantis last week during a signing ceremony claimed the “gender bread man” was invading Florida classrooms and young students were being taught to doubt their gender identity.

Responding to Fine’s tweets on Monday, state Rep. Anna Eskamani, a Democrat, said Florida Republicans are “once again showing us that the entire premise of HB1557 was & is to attack the health & well-being of LGBTQ+ youth, who they don’t think should even be able to access medical care w/parental consent.”

“This policy proposal is dangerous & will harm already marginaliz[ed kids],” Eskamani wrote on Twitter, attaching a screenshot of Fine’s initial message pledging to punish providers of gender-affirming care.

More than a dozen states are currently debating whether transgender and nonbinary minors should have access to gender-affirming care, which has been identified as best practice by most major medical associations.

Importantly, the World Professional Association for Transgender Health does not recommend interventions like surgery be carried out before a person seeking gender-affirming care reaches the “legal age of majority,” which in most countries is 18 years old.

https://thehill.com/changing-america/respect/equality/3258881-florida-lawmaker-vows-to-make-gender-affirming-care-for-minors-felony-child-abuse/

ACC: iRhythm’s Zio ECG patch catches arrhythmia

 More than a decade after first earning the FDA’s sign-off for its Zio ECG patch, iRhythm is still churning out data to prove beyond a shadow of a doubt the heart monitor’s ability to spot atrial fibrillation and other arrhythmias as early as possible. The latest bit of proof came in the form of a trio of studies presented at the American College of Cardiology’s annual scientific meeting.

The research shows that the two-week, artificial intelligence-powered Zio system doesn’t just aid in diagnosing afib in patients with a standard risk level, but also helps monitor higher-risk patients after cardiac and other procedures, potentially saving hospitals time, money and bed space.

“We are excited that these new data continue to demonstrate that Zio’s clinical accuracy is beneficial in directing patient care across a variety of settings while improving clinical workflows and hospital capacity. We are also particularly encouraged to see further evidence of Zio’s ability to support early detection and diagnosis of AF in moderate-risk populations,” said Dietra Jones, iRhythm’s executive VP of clinical operations.

One set of results came from the GUARD-AF study and comprised data from more than 5,700 patients aged 70 and older—"the largest sample of patch monitor AF screening to date,” according to the study—with a moderate risk of developing afib.

Though none of the patients had previously been diagnosed with the arrhythmia, after 14 days of monitoring with the Zio patch, nearly 5% were found to have signs of afib. Additionally, 30 of the patients had 100% afib, also called persistent afib, in which symptoms last longer than seven days at a time.

Another study used iRhythm’s device to look for certain complications after a transcatheter aortic valve replacement procedure, including afib, high-degree atrioventricular block and supraventricular tachycardia. “Little is known” about the clinical impact of contracting the latter two after a TAVR procedure, the study’s authors said.

Following the patients for two weeks after the procedure with the Zio patch’s ECG readings helped establish patterns determining the risk of contracting either of those conditions, per the study, proving that the patch should then be used in the future to monitor high-risk cases.

The third study also followed patients after a hospital stay, focusing on those with syncope, a condition that causes fainting. In that case, 183 patients were given the Zio patch to wear for 14 days after being discharged from the emergency room.

Just over 8% of the patients experienced arrhythmia events that triggered an alarm to their healthcare providers, but the overwhelming majority of those events occurred at least 24 hours after discharge, proving that it may be unnecessary for many syncope patients to stay at the hospital for extra days of observation after visiting the ER. In total, the study found, the experiment saved the health system 136 days’ worth of inpatient resources.

https://www.fiercebiotech.com/medtech/acc-irhythms-zio-ecg-patch-catches-arrhythmia-older-patients-after-tavr-implant

Sanofi, Regeneron score fast FDA review for Dupixent in eosinophilic esophagitis

 Already with approvals in hand for eczema, asthma and rhinosinusitis, Dupixent has quickly become one of the most important drug in the portfolios of Sanofi and its antibody partner Regeneron.

Now Dupixent appears to be closing in on a fourth indication with the FDA’s acceptance—and priority review award—of the partners' Dupixent application to treat eosinophilic esophagitis (EoE).

Dupixent has been on a successful track since 2017 when it was granted orphan drug status for EoE. Breakthrough designation came from the FDA in September of 2020.

There is no medicine approved specifically for the disorder in the U.S., where it affects 160,000 people, including 48,000 who have failed multiple treatments.

The inflammatory disease damages the esophagus and makes swallowing difficult. The application is for those 12 and older at a 300 mg dose. The target date for a decision is August 3.

The application is supported by two phase 3 trials. Data from one were revealed in February at the American Academy of Allergy, Asthma and Immunology (AAAAI) conference. The results showed Dupixent trumped placebo in improving EoE symptoms at the 24-week mark.

In the study, which included 159 participants, 64% of those on the monoclonal antibody saw a reduction in disease symptoms compared with 41% in the control arm. Those on Dupixent also had a 23.8-point improvement on a dysphagia symptom questionnaire—which measures difficulty in swallowing—versus a 13.9-point improvement for those in the placebo group.

In addition, nearly 10 times as many patients on Dupixent hit histological disease remission at 59%, versus just 6% in the control arm.

The safety profile of Dupixent remained consistent with that seen in its other indications, with the most common side effect being injection-site reactions.

Last year, Dupixent registered sales of 5.25 billion euros ($6 billion), a 53% increase on 2020, Sanofi said in its annual report (PDF) in February. Last month, the company projected its peak sales will hit 13 billion euros or more.

https://www.fiercepharma.com/pharma/sanofi-gains-priority-review-dupixent-treat-treat-eosinophilic-esophagitis-potential-fourth

Supernus Reiterates Full Year 2022 Financial Guidance

 Supernus Pharmaceuticals, Inc. (Nasdaq: SUPN), a biopharmaceutical company focused on developing and commercializing products for the treatment of central nervous system (CNS) diseases, today announced that it expected to file its Annual Report on Form 10-K for the fiscal year ended December 31, 2021 (the “Annual Report”) in the near term.

Full Year 2022 Financial Guidance (GAAP)

The Company reiterates the full year 2022 financial guidance initially announced on February 28, 2022 as set forth below:

	Amount ($ in millions)
Total revenues (1)	$640 - $680
Combined R&D and SG&A expenses	$460 - $490
Operating earnings (2)	$20 - $40
Effective tax rate	25% - 28%

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(1) Includes net product sales and royalty revenue.
(2) Includes amortization of intangible assets and contingent consideration expense (gain).

Full Year 2022 Financial Guidance — GAAP to Non-GAAP Adjustments

An itemized reconciliation between projected operating earnings on a GAAP basis and projected operating earnings on a non-GAAP basis is as follows:

	Amount ($ in millions)
Operating earnings - GAAP	$20 - $40
Adjustments:
Amortization of intangible assets	$80 - $85
Share-based compensation	$20 - $25
Contingent consideration	$8 - $12
Depreciation	$2 - $3
Operating earnings - non-GAAP	$130 - $165

https://finance.yahoo.com/news/supernus-provides-filing-annual-report-210000831.html