Cell-Based Flu Vax Not Superior to Egg-Based Vax in Study

Cell culture-based inactivated influenza vaccine (IIV) was not significantly more effective than egg-based IIV against influenza A during the 2017-2018 flu season, a researcher said here.

The relative vaccine effectiveness of cell culture-based IIV versus egg-based IIV against influenza A was 8% (HR 0.92, 95% CI -10% to 23%, P=0.36), but the difference between the two was non-significant, Nicola Klein, MD, of Kaiser Permanente in Oakland, California, reported.

The study was a late-breaking presentation at IDWeek, with joint sponsorship by the Infectious Diseases Society of America (IDSA), the Pediatric Infectious Diseases Society(PIDS), the Society for Healthcare Epidemiology of America (SHEA), and the HIV Medicine Association (HIVMA).

Klein said that reports from the CDC indicated that vaccine effectiveness (VE) against the predominant strain in the 2017-2018 season, influenza A (H3N2), was around 24% on average. She added that “this lower-than-expected VE was hypothesized to be partially related to genetic changes arising in the vaccine during passage in eggs,” and that this “raises the question of whether cell-culture based inactivated influenza vaccines are more effective.”

In a separate video interview unrelated to the study, William Schaffner, MD, professor of preventive medicine and infectious diseases at Vanderbilt University in Nashville, spoke in general about upcoming advances in flu vaccines — characterizing the current flu vaccine as “good, but not great.” Schaffner touched on the hope surrounding new technologies, such as cell-based vaccines.

“[These] vaccines are going to be created, not in the ancient way of manufacturing them in eggs, but in other modalities. It’s really kind of remarkable — that might get us better antigens,” he told MedPage Today. “Anything we can do to improve the quality of the vaccine I think will lead to … more enthusiasm on the part of the provider to actually get everybody vaccinated.”

Klein and colleagues examined the effectiveness of the currently available cell culture-based IIV Flucelvax (manufactured by Seqirus) as compared with an egg-based IIV among members of Kaiser Permanente Northern California (KPNC), ages 4-64 years. Members were followed through the end of the the 2017-2018 influenza season, disenrollment from KPNC or death. A positive influenza PCR test was defined as influenza positive.

They compared both vaccines in a head-to-head comparison (relative vaccine effectiveness), as well as each vaccine separately with unvaccinated individuals (absolute vaccine effectiveness).

Overall, there were over 3 million total people, ages 4-64, in the study, with about 1 million vaccinated. Of those vaccinated, about 8.3% received cell culture-based IIV.

Moreover, there were about 5,800 who were influenza A-positive and about 70% of those were unvaccinated. About a quarter received egg-based vaccine and 2.4% received cell culture-based vaccine.

While there was no significant difference between vaccine types, when compared with unvaccinated persons, absolute vaccine effectiveness of cell culture-based vaccine (31.7%, 95% CI 18.7%-42.6%, P<0.0001) and egg-based IIV (20.1%, 95% CI 14.5%-25.4%, P<0.0001) was significantly higher for both for influenza A.

Researchers also compared both relative and absolute vaccine effectiveness against influenza B. While relative vaccine effectiveness of the cell-culture based vaccine was 39.6% (95% CI 27.9%-49.3%, P<0.0001), this was compared with the egg-based trivalent vaccine, which contained B virus of Victoria lineage.

Absolute vaccine effectiveness was 40.9% versus unvaccinated people for cell-cultured based vaccine (95% CI 30.0%-50.1%, P<0.0001), but 9.7% for the egg-based trivalent vaccine (95% CI 3.5%-15.6%, P=0.0028).

However, Klein said that 83% of B viruses in Northern California were Yamagata strain, so these numbers were “about what we’d expect, given what circulated in the season.”

She concluded that the data hinted that cell culture-based vaccine was “moderately more effective” against influenza A than egg-based vaccines, but the difference was non-significant, and that this vaccine provided “good effectiveness” against influenza B.

“Ongoing monitoring of vaccine effectiveness is crucial, but most of all, we need better vaccines,” Klein said.

The study was partially supported by the Department of Health and Human Services, the Office of the Assistant Secretary for Preparedness and Response, and the Biomedical Advanced Research and Development Authority (BARDA).

Klein disclosed support from Sanofi Pasteur, GlaxoSmithKline, Pfizer, Merck, Protein Sciences (now Sanofi Pasteur), MedImmune, and Dynavax.

• Primary Source

  IDWeek

  Source Reference: Klein N, et al “Vaccine effectiveness of flucelvax relative to inactivated influenza vaccine during the 2017-18 influenza season in Northern California” IDWeek 2018; Abstract LB15.

https://www.medpagetoday.com/meetingcoverage/idweek/75583

Opioid-Benzo Overlap Higher in Patients Using Multiple Health Systems

Receiving drugs from more than one healthcare system was tied to a greater risk of overlapping prescriptions for opioids and benzodiazepines, a cross-sectional study showed.

Receiving prescriptions from both the U.S. Department of Veterans Affairs (VA) and Medicare Part D in 2013 carried a 27% increased risk for overlapping opioids and benzodiazepines, compared with receiving prescriptions from the VA alone, according to Walid Gellad, MD, MPH, of the VA Pittsburgh Healthcare System, and colleagues.

Using two healthcare systems also was linked to a higher risk of overlapping high-dose opioids with benzodiazepines, they reported in Annals of Internal Medicine.

“We could not identify what might be causing the increased risk of overlapping prescriptions, although we noticed that the more prescriptions were split between VA and Medicare, the higher the risk, suggesting that perhaps care fragmentation and lack of communication are contributing to overlapping prescriptions,” Gellad told MedPage Today.

Benzodiazepines can increase the respiratory depressant effects of opioids: a recent review of health claims data showed that among opioid users, concurrent use of benzodiazepines more than doubled the risk of an overdose-related emergency department or inpatient visit. Both prescription opioids and benzodiazepines now carry FDA boxed warnings highlighting the dangers of using the drugs together. While prescription drug monitoring program (PDMP) checks often are required before opioid prescriptions, this is not uniformly the case for benzodiazepines.

In this study of 368,891 veterans who were enrolled in both VA and Medicare programs, and who filled at least two opioid prescriptions with >15 days of total opioid exposure in 2013, 18.3% received prescriptions from the VA only, 30.3% from Medicare only, and 51.4% from both plans. Sublingual buprenorphine formulations were not included in the analysis and patients who received hospice or palliative care were excluded from the study.

The researchers looked for patients with a Pharmacy Quality Alliance (PQA) measure of opioid-benzodiazepine overlap (≥2 filled prescriptions for benzodiazepines with ≥30 days of overlap with opioids) and patients with high-dose opioid–benzodiazepine overlap (≥30 days of overlap with a daily opioid dose >120 morphine mg equivalents).

Opioid-benzodiazepine overlap was greater for patients who used both systems than those who used only the VA (23.1% versus 17.3%, adjusted RR 1.27, 95% CI 1.24-1.30) or used only Medicare (23.1% versus 16.5%, adjusted RR 1.12, 95% CI 1.10-1.14).

High-dose opioid overlap also was greater for the dual-use group than the VA-only group (4.7% versus 2.3%, adjusted RR 2.23, 95% CI 2.10-2.36) or Medicare-only group (4.7% versus 2.9%, adjusted RR 1.06, 95% CI 1.02-1.11).

This study illustrates an important component of the opioid problem, observed Anna Lembke, MD, of Stanford University School of Medicine in California, who was not involved with the research. “Patients commonly see multiple doctors in different treatment settings, and those various doctors don’t always know what the other one is prescribing,” she told MedPage Today.

“The solution is to make PDMP databases more transparent and interoperable across systems and geographic boundaries, and to mandate that prescribers check the databases before prescribing, not just for opioids, but also benzodiazepines,” Lembke added. “Mandating that doctors check the database also means recognizing that docs are already overburdened with bureaucratic overhead, so the databases need to be easy to use and integrated into existing electronic medical records.”

Clinicians also need to pay careful attention to patients who receive both drugs, added Mark Olfson, MD, MPH, of Columbia University Medical Center in New York City, who was not involved in the study.

“Physicians should remain ever vigilant for sleep-disordered breathing in these patients,” Olfson told MedPage Today. “Sleep apnea is quite common among patients receiving long-term opioid therapy or high-dose benzodiazepine regimens. To reduce risk, efforts should be made to reduce opioid dose, substitute non-opioid analgesics whenever possible, and avoid use of alcohol and sedatives.”

While this study used the most recent data available, the 2013 records are “prior to the rapid uptake of PDMPs across the country and prior to robust use of PDMPs across the VA,” Gellad said. “It remains to be seen whether PDMPs can help limit these overlaps within VA.”

The study had several limitations: it may have underestimated overlap because it did not capture drugs purchased without insurance or illicitly. Recent trends, like the VA’s Opioid Safety Initiative, may have altered opioid-benzodiazepine use since 2013. And unmeasured confounding may have existed, despite the study’s robust statistical methods, the researchers added.

The study was funded by a grant from the VA’s Health Services Research and Development Service.

Gellad and some co-authors disclosed support from the VA.

• Primary Source

  Annals of Internal Medicine

  Source Reference: Carico R, et al “Receipt of overlapping opioid and benzodiazepine prescriptions among veterans dually enrolled in Medicare Part D and the Department of Veterans Affairs: A cross-sectional study” Ann Intern Med 2018; DOI:10.7326/M18-085.

https://www.medpagetoday.com/neurology/opioids/75580

Perrigo (PRGO) Names Murray S. Kessler As President and CEO

• Murray S. Kessler, former Chief Executive Officer and President at the Lorillard Tobacco Company, appointed President, CEO and member of the Board of Directors effective immediately

• • Proven track record for over 30 years in leadership positions among multiple consumer products goods companies

• • Experience aligned with Perrigo’s consumer-focused strategy and commitment to separation of the Rx business

• Uwe Roehrhoff steps down as President, CEO and board member; will remain available to ensure a smooth transition

Perrigo Company plc (NYSE: PRGO), a leading global provider of Quality Affordable Healthcare Products®, today announced the appointment of Murray S. Kessler as President, CEO and member of the Board of Directors, effective immediately.

Chairman of the Board of Directors, Rolf Classon, stated, “We are excited to have Murray Kessler, a highly successful business executive, join Perrigo as its next CEO. Given the decision to separate the Rx pharmaceuticals business and pursue a consumer-focused strategy, the Board is looking forward to partnering with him to develop Perrigo’s strategic plan. Murray joins Perrigo with more than 30 years of leadership experience in growing consumer products companies and managing businesses in a regulated environment. He has advanced corporate strategy through innovation, inorganic opportunities, and continuous portfolio improvement. We are confident that his track record in driving shareholder value and running highly successful businesses will advance Perrigo’s consumer strategy and help the Company deliver on our commitments to consumers and customers.”

Mr. Kessler most recently served as the Chairman of the Board of Directors and CEO of Lorillard Tobacco Company (2010-2015). As a leading innovator in the industry, Mr. Kessler spearheaded the company’s expansion into new and emerging categories, growing Lorillard’s market capitalization from approximately $9 billion to approximately $28 billion during his tenure. Prior to joining Lorillard, Mr. Kessler served as Vice Chair of Altria, Inc. and President and CEO of UST Inc., a wholly owned subsidiary of Altria since 2009. Mr. Kessler originally joined UST in 2000 and was promoted to the role of President of the division within one year. In 2005, Mr. Kessler was appointed COO of UST, and served as CEO from 2007 to 2009. During his tenure, market capitalization grew from approximately $2.5 billion to approximately $12.7 billion.

Before joining UST, Mr. Kessler had more than 18 years of consumer packaged goods experience with several well-known consumer companies, including Vlasic Foods International, Campbell Soup Company and The Clorox Company. He earned a Bachelor of Business Administration degree from Villanova University and a Master of Business Administration degree from the New York University Stern School of Business.

Newly appointed CEO and President of Perrigo, Murray Kessler, commented, “This is a rare opportunity to drive winning results with a passionate and committed team in a high potential, consumer focused company that holds a leadership position in a broad portfolio of sizeable and recognizable categories. My experience in working with highly regulated consumer products reinforces my belief in this opportunity and it is for these reasons that I have chosen to once again take on the deep commitment of being a public company CEO. I look forward to working with the talented Perrigo leadership team and the Board to put a plan in place that delivers long-term sustainable and reliable growth.”

Mr. Classon concluded, “The Board and Uwe mutually agreed the transition was in the best interest of the Company and, given the previously announced separation of the Rx business, now is the appropriate time to make this change. The Board determined that Murray is the right CEO for Perrigo’s consumer focused strategy going forward. We are thankful for Uwe’s leadership, including the decision to separate the Rx business. We are grateful for his service and wish him the best in his future endeavours.”

Mr. Roehrhoff stepped down as President, CEO and board member and will make himself available to ensure a smooth and successful transition.

https://www.streetinsider.com/Corporate+News/Perrigo+%28PRGO%29+Names+Murray+S.+Kessler+As+President+and+CEO/14683991.html

Novo Nordisk initiated at Guggenheim

Novo Nordisk initiated with a Buy at Guggenheim. Guggenheim analyst Seamus Fernandez started Novo Nordisk with a Buy rating and DKK 361 price target, stating that he expects quality growth through 2020 and beyond ” as long as GLP-1 category price discipline remains.”
https://thefly.com/landingPageNews.php?id=2801217

Celgene says Phase 3 Otezla study meets primary, secondary endpoints

Celgene Corporation announced results from the phase 3 STYLE study, which showed that Otezla 30 mg twice daily achieved a highly statistically significant improvement in the primary endpoint of the Scalp Physician’s Global Assessment response [defined as ScPGA score of clear or almost clear with at least a 2-point reduction from baseline] at week 16 compared with placebo. In addition to achieving the primary endpoint, statistical significance was also met for the secondary endpoint of the whole body itch numeric rating scale at week 16 with Otezla versus placebo. The safety profile was generally consistent with the known safety profile of Otezla, and no new safety signals were identified in the trial.
https://thefly.com/landingPageNews.php?id=2801229

Altimmune Shares Volatile After Presentation of Positive Flu Vaccine Data

Altimmune Inc ALT 31.77% shares have been on a roller coaster ride since mid-September, swinging in a wild range of $26.23 to $4.27.

The shares were jumping 28.87 percent to $9.33 in premarket trading Monday before falling more than 30 percent to $5.06 after the open.

What Happened

Altimmune presented an oral abstract on its intranasal influenza vaccine NasoVax at the IDWeek conference held in San Francisco over the weekend.

The presentation made Oct. 6 showed that NasoVAX was well-tolerated and elicited comparable antibody responses and nearly sixfold higher cellular immune response than Sanofi SA SNY 0.41%‘s Fluzone injectable influenza vaccine.

The Phase 2 study evaluated 60 healthy adults randomized to three doses of monovalent NasoVAX formulations or saline placebo, all given as a 0.25 ml nasal spray in each nostril. A parallel cohort of 20 subjects were dosed with Fluzone.

The study participants were assessed for safety, including solicited local and systemic side effects.

The immune responses studied included hemagglutination inhibition and neutralizing antibody at days one, 15, 29, 90 and 180, and ɣ-interferon ELISpot at days one and eight.

What’s Next

Citing the additional positive Phase 2a data released in early September, Altimmune said it expects to initiate additional Phase 2 studies in 2019.

https://www.benzinga.com/general/biotech/18/10/12471156/altimmune-shares-volatile-after-presentation-of-positive-flu-vaccine-

FDA puts Affimed AFM11 phase 1 program on hold after patient death

https://thefly.com/landingPageNews.php?id=2801194