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Thursday, November 3, 2022

CDC Just Changed Its Opioid Prescribing Guidelines

 Hard thresholds for pain medication doses and duration are no longer promoted through the CDC's new Clinical Practice Guideline for Prescribing Opioids for Pain.

The new guidance -- which covers acute, subacute, and chronic pain for primary care and other clinicians -- updates and replaces the controversial 2016 CDC opioid guideline for chronic pain. The 2016 guideline was interpreted as imposing strict opioid dose and duration limits and was misapplied by some organizations, leading the guideline authors to clarify their recommendations in 2019.

The 2022 recommendations are voluntary and give clinicians and patients flexibility to support individual care, said Christopher Jones, PharmD, DrPH, MPH, acting director of CDC's National Center for Injury Prevention and Control in a CDC press briefing. They should not be used as an inflexible, one-size-fits-all policy or law, or applied as a rigid standard of care, or replace clinical judgement about personalized treatment, he emphasized.

"Patients with pain should receive compassionate, safe, and effective pain care," Jones stated. "We want clinicians and patients to have the information they need to weigh the benefits of different approaches to pain care, with the goal of helping people reduce their pain and improve their quality of life."

The guidance, published in Morbidity and Mortality Weekly Report, addresses four key areas: initiating opioids for pain, selecting opioids and dosages, deciding prescription duration and conducting follow-up, and assessing risk and potential harms of opioids. It suggests that clinicians work with patients to incorporate plans to mitigate risks, including offering naloxone.

The 100-page document indicates opioids should not be considered as first-line or routine therapy for subacute or chronic pain, and points out that non-opioid therapies often are better for many types of acute pain.

"For patients receiving opioids for 1 to 3 months (the timeframe for subacute pain), the 2022 guideline recommends that clinicians avoid continuing opioid treatment without carefully reassessing treatment goals, benefits, and risks in order to prevent unintentional initiation of long-term opioid therapy," wrote Debbie Dowell, MD, MPH, chief clinical research officer for CDC's Division of Overdose Prevention, and guideline co-authors in a commentary published in the New England Journal of Medicine.

For chronic pain, clinicians should maximize use of non-opioid therapies and consider initiating opioid therapy only if the expected benefits for pain and function are anticipated to outweigh the risks, Dowell and colleagues noted. When opioids are needed for chronic pain, clinicians should start at the lowest effective dose, evaluate benefits and risks before increasing dosage, and avoid raising dosage above levels likely to yield diminishing returns, they added.

"These principles do not imply that nonpharmacologic and non-opioid pharmacologic therapies must all be tried unsuccessfully in every patient before opioid therapy is offered," Dowell and colleagues wrote. "Rather, expected benefits specific to the clinical context should be weighed against risks before therapy is initiated."

The new guideline offers tips for tapering opioids when warranted, but is not intended to lead to rapid opioid tapering or discontinuation, Jones noted. The recommendations do not apply to sickle cell disease-related pain, cancer pain, and palliative or end-of-life care.

The 2022 document incorporated feedback from approximately 5,500 public comments since the new version was first proposed in February, including reactions from people who discussed their experiences with pain or opioid addiction and barriers to pain care. An independent federal advisory committee, four peer reviewers, and members of the public reviewed the draft version.

"The science on pain care has advanced over the past 6 years. During this time, CDC has also learned more from people living with pain, their caregivers, and their clinicians," Dowell said in a statement. "We've been able to improve and expand our recommendations by incorporating new data with a better understanding of people's lived experiences and the challenges they face when managing pain and pain care."

The clinical practice guideline supports the HHS Overdose Prevention Strategy, the CDC said. The agency also is providing additional information associated with the guideline to clinicians and patients.

Disclosures

RegenxBio: Zolgensma revenues disappoint

 Revenues: Revenues were $26.5 million for the three months ended September 30, 2022, compared to $30.8 million for the three months ended September 30, 2021. The decrease was primarily attributable to Zolgensma royalty revenues, which decreased from $30.3 million for the third quarter of 2021 to $25.2 million for the third quarter of 2022. Zolgensma royalty revenues for the nine months ended September 30, 2022 were $75.1 million for the nine months ended September 30, 2022, compared to $66.9 million for the nine months ended September 30, 2021.

https://www.biospace.com/article/releases/regenxbio-reports-third-quarter-2022-financial-results-and-recent-operational-highlights/?keywords=regenxbio

Regeneron Pulls the Plug on Osteoarthritis and Cat Allergy Therapies

 Regeneron Pharmaceuticals has pulled the plug on an experimental osteoarthritis pain treatment that raised some safety flags during years of clinical development, the company announced in its third quarter report Thursday. 

The investigational drug in question, fasinumab, was being evaluated in late-stage studies for the treatment of osteoarthritis of the knee or hip and chronic low back pain in patients with concomitant osteoarthritis of the knee or hip.

During clinical trials dating back a decade, the antibody designed to target Nerve Growth Factor (NGF), a protein that plays a central role in regulating pain signaling, was beset with multiple safety issues.

In 2012, the FDA placed fasinumab and other investigational anti-NGF agents on partial clinical hold due to reports of sympathetic nervous system toxicity in mature animals being treated with other NGF antibodies. 

Six years ago, the FDA placed a Phase IIb study on clinical hold after observing a case of adjudicated arthropathy, a disease of the joint. That patient had been receiving a high dose of fasinumab during the clinical program.

Two years later, Regeneron announced it had halted high-dose treatment of fasinumab in a late-stage program following a risk-benefit assessment conducted by an Independent Data Monitoring Committee.

Regeneron did not offer additional details on why it pulled the plug on its clinical programs for this antibody. 

Regeneron was not developing fasinumab alone. In 2016, Teva Pharmaceuticals handed over $250 million to partner with Regeneron on the development of fasinumab. One year before that, Regeneron and Mitsubishi Tanabe Pharma Corporation entered into a licensing agreement for the anti-NGF antibody. 

Cat Allergy Antibody Reaches Futility

Beyond fasinumab, Regeneron also pulled the plug on its experimental treatment for people with cat-allergic asthma. The company noted the study of the experimental anti-Fel d 1 treatment was halted due to futility. The Phase III trial was assessing a single dose of REGN1908-1909 compared to placebo. 

Cat allergy is primarily caused by exposure to Fel d 1, which is the major allergen in cat dander. Last year, the company posted positive Phase IIa data at the 2021 American Academy of Allergy, Asthma and Immunology meeting. 

Beyond the termination of the two programs, Regeneron saw a 15% decrease in revenue, primarily due to declining sales of its COVID-19 treatment, REGEN-COV. Overall, sales for the quarter were $2.94 billion. If REGEN-COV was not factored into the company's revenue stream, Regeneron's quarterly sales would have increased by 11%, the company reported. 

Overall, Regeneron is set to close out the year's final quarter with positive momentum. The company has approximately 35 product candidates in clinical development, including several marketed products for which it is investigating additional indications.

https://www.biospace.com/article/regeneron-pulls-the-plug-on-osteoarthritis-and-cat-allergy-therapies-/

Moderna Loses AstraZeneca's Support in IL-2 Program, must Defend Arbutus Suit

 Moderna is re-evaluating an IL-2 program in autoimmune disorders after AstraZeneca returned the rights, the mRNA leader announced Thursday in its third quarter filing

Details regarding the decision involving the mRNA therapy for IL-2-based autoimmune disorders were scant, with the company only saying it is "evaluating next steps for the program," according to the Q3 announcement. 

MEDI1191 was being developed by AstraZeneca's MedImmune division with anti-PD-L1 checkpoint inhibitor durvalumab in advanced solid tumors. MEDI1191 is a lipid nanoparticle-formulated therapy designed to drive local IL-12 production and induce anti-tumor activity. 

On Aug. 1, AstraZeneca killed another program with Moderna. AZD8601, an mRNA therapy that encoded vascular endothelial growth factor (VEGF-A),  was a Phase II drug candidate. The drug was injected directly into the myocardium of patients receiving elective coronary artery bypass surgery.

Moderna shares dropped 12% after the company lowered sales guidance for its COVID-19 vaccine. Moderna projected $18 billion to $19 billion in revenue from the vaccine, its sole commercial product, for 2022.  

This is compared to the $21 billion guidance the company initially provided. Moderna indicated that some vaccine deliveries had been delayed into 2023 because of supply issues.

Third-quarter revenue was $3.36 billion, down 32% from the same period in 2021. 

Moderna also focused on a Phase II readout expected by the end of the year for mRNA-4157/V940 in combination with Merck's anti-PD-1 checkpoint inhibitor Keytruda. The study is evaluating the combination as adjuvant treatment for patients with high-risk melanoma. 

Moderna Must Defend Arbutus Suit 

In related news, a Delaware federal judge ruled Wednesday that Moderna - not the U.S. government - must face patent lawsuits brought by Arbutus Biopharma and Genevant Sciences GmbH.

A Moderna spokesperson told BioSpace  "the company looks ahead to proving not only that Arbutus and Genevant sued the wrong party in the wrong court, but also, at the appropriate time, that there was no patent infringement here." 

https://www.biospace.com/article/moderna-cuts-autoimmune-program-in-q3-announcement-astrazeneca-returns-cancer-program/

Surgalign cuts outlook

 “Market challenges, particularly in Europe, coupled with the push out of HOLO Portal procedures has led us to revise our 2022 revenue guidance lower, though we anticipate sequential top-line improvement. Our number one priority from a corporate perspective, is ensuring we have the financial resources to carry through on our strategy as we transition to digital health. We remain in discussions with several parties and hope to have additional funding in place prior to year-end, though we may look at other measures in the short-term to provide additional time to consummate a third-party financing. In the interim, we continue to lower our expenses, without sacrificing innovation.”

https://finance.yahoo.com/news/surgalign-announces-third-quarter-2022-200100052.html

VapoTherm misses in Q3, lowers guidance

 VapoTherm (NYSE:VAPO) shares fell this morning on third-quarter results that came up short of the consensus forecast.

The Exeter, New Hampshire-based company posted losses of $91.8 million. That equals 98¢ per share on sales of $13.55 million for the three months ended Sept. 30, 2022.

VapoTherm registered a massive bottom-line slide deeper into the red on a sales decline of 64.5%. The company attributed year-over-year revenue declines as the Delta variant of COVID-19 drove demand for the company’s products this time last year. That failed to repeat in the three-month period this year.

The company’s losses per share of 98¢ came in 20¢ behind expectations on Wall Street. Analysts projected revenues of $13.54 million.

“Our revenue increased sequentially from the second quarter to the third quarter which is not typical given the seasonality in our business,” said Joseph Army, president and CEO. “Growth was driven primarily by consistent monthly improvement in U.S. disposables turn rates… and the ongoing launch of our new product platform HVT 2.0. … We are on track to complete the move of operations to Mexico by year-end which we believe will improve our gross margins to 60% once we work through our higher costed inventory and initial production builds.”

Vapotherm expects a net revenue range between $64 million and $66 million. The previous guidance fell between $75 million and $81 million. Its guidance reflects a light flu season which typically begins in the fourth quarter in the U.S. The guidance does not reflect any significant COVID-19 impact.

BTIG analyst Marie Thibault wrote that she maintains her “Neutral” rating on VapoTherm. Its guidance, among other issues, offset positive news in its third-quarter results, she said.

“We remain concerned with the revenue covenant overhang, the need to quickly convert inventory to cash, and long-term efforts needed to reach profitability,” wrote Thibault.

Shares of VAPO dipped 21.8% at $1.65 apiece in early-morning trading today. MassDevice’s MedTech 100 Index — which includes stocks of the world’s largest medical device companies — fell by 4%.

https://www.massdevice.com/vapotherm-q3-2022-guidance/

Pfizer, BioNTech start COVID-flu combination vaccine study

U.S. drugmaker Pfizer Inc and its German partner BioNTech SE have started an early-stage study to evaluate a combination vaccine targeting COVID-19 and influenza, the companies said on Thursday.

The single-dose vaccine candidate is a combination of Pfizer's mRNA-based flu shot and the companies' Omicron-tailored COVID-19 booster shot.

The early-stage study, which is being sponsored by BioNTech, aims to evaluate the combination shot's safety, tolerability and immunogenicity, or the ability to generate immune response.

The trial is being conducted in the United States and the companies aim to enroll 180 volunteers between the ages of 18 and 64. The first participant in the study was dosed earlier this week.

Rivals Moderna Inc and Novavax Inc are also developing combination vaccines targeting both COVID-19 and influenza

https://finance.yahoo.com/news/1-pfizer-biontech-start-covid-111728370.html