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Sunday, August 26, 2018

FDA Action Alert: Ortho Dermatologics, Tetraphase Pharma, Akcea and More


This week has several action dates by the U.S. Food and Drug Administration (FDA) for a range of indications, including acne, intra-abdominal infections, and rare liver diseases. Here’s a look.
Bausch Health Companies’ (formerly Valeant Pharmaceuticals) Ortho Dermatologicsdivision has a PDUFA action date of Monday, August 27, 2018, for its New Drug Application (NDA) for Altreno. Altreno, if approved, will be the first tretinoin product in lotion form instead of a gel or crème. Altreno is a treatment for acne.
“More than 4 million patients make appointments with dermatologists each year or acne,” said Joseph Papa, Valeant chairman and chief executive officer, in a statement in January. “It is our goal to be the go-to resource for doctors and patients for all dermatological conditions, and if approved, Altreno will be a valuable addition to the Ortho Dermatologics portfolio.”
TetraPhase Pharmaceuticals has a PDUFA date for its NDA for eravacycline for complicated intra-abdominal infections (cIAI). The NDA submission included data from IGNITE1 and IGNITE4 Phase III clinical trials, which compared twice-daily IV eravacycline to ertapenem in IGNITE1 and meropenem in IGNITRE4. Eravacycline is a novel, fully-synthetic fluorocycline antibiotic developed to treat cIAI and other serious infections, including infections caused by multidrug-resistant (MDR) pathogens.
“The FDA’s acceptance for review of our NDA submission for IV eravacycline in cIAI marks an important step in our goal to bring this important new treatment option to patients in need,” said Guy Macdonald, Tetraphase’s president and chief executive officer, in a statement in February. “We believe that eravacycline has the potential to play a key role in the treatment of serious intra-abdominal infections, particularly Gram-negative infections, and we look forward to providing an update on a regulatory decision in August as we continue to prepare for a commercial launch.”
On July 27, the European Medicines Agency (EMA)’s Committee for Medicinal Products for Human Use (CHMP) reported a positive opinion recommending Xerava (eravacycline) for approval for cIAI. A decision should be made by the end of November by the EMA.
Akcea Therapeutics, an affiliate of Ionis Pharmaceuticals, has a PDUFA target date of August 30, 2018, for Waylivra (volanesorsen) for patients with familial chylomicronemia syndrome (FCS). FCS is a severe, rare disease characterized by extremely high triglyceride levels and symptoms such as extreme abdominal pain. There is also a risk of recurrent, potentially fatal, acute pancreatitis.
The same time the NDA was accepted for review by the FDA, it was accepted by the EMA and Canada’s regulatory agency, Health Canada. Health Canada gave it Priority Review and the United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA) granted it a Promising Innovative Medicine (PIM) Designation.
“We are committed to seeking global approvals for volanesorsen at the outset,” said Paula Soteropoulos, Akcea’s chief executive officer, in a November 2017 statement. “The acceptances of our regulatory filings in the U.S., EU and Canada are important steps forward in the global regulatory review process for volanesorsen, which brings us closer to potentially providing the first approved therapy for the treatment of people with FCS.”
The drug is designed to decrease the production of ApoC-III, a liver protein that’s involved in the regulation of plasma triglycerides. It is also under development for FPL, another severe, rare genetic metabolic disorder characterized by the body’s inability to store fat in normal locations. Individuals with FPL are at increased risk of acute pancreatitis as well as long-term, progressive diseases such as premature cardiomyopathy, atherosclerosis, and liver disease.
It was announced on August 2 that Akcea and PTC Therapeutics were collaborating to commercialize two of Akcea’s drugs in Latin America, Tegsedi (inotersen) and Waylivra. Tegsedi has a PDUFA date of October 6, 2018, for the treatment of stage 1 or stage 2 polyneuropathy in adult patients with hereditary transthyretin amyloidosis (hATTR amyloidosis).
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Harbour BioMed Raises $85M in Series B Financing to Accelerate Pipeline


Harbour Biomed announced today that it has completed a Series B round financing of $85 million to accelerate the growth of its innovative therapeutic pipeline, including both clinical and discovery stage programs. GIC Private Limited, Singapore’s sovereign wealth fund, led the financing round, with participation from new investors, including China Life Private Equity Investment Company and Vertex Ventures, and Series A investors AdvanTech and Legend Capital.
“During the one and half years since we established operations, Harbour has successfully expanded its network of collaborations for its core transgenic mouse technologies, rapidly built an innovative pipeline through internal discovery and in-licensed development stage programs in the areas of oncology and immunology, and established an experienced and professional team,” said Dr. Jingsong Wang, the Founder, Chairman and CEO of Harbour BioMed. “The financing is a very strong vote of confidence by our new and existing investors in our vision for the company, strategy, progress to date and our team. With their continued support, we will accelerate the growth and advancement of our pipeline through both internal innovation and external collaboration.”
Harbour BioMed was established in December 2016 around a Series A round of $50 million and the acquisition of the Netherlands-based fully human transgenic antibody technology company, Harbour Antibodies BV and its subsidiaries. The company has integrated the Harbour Mice technologies into its newly built antibody technology and discovery biology, preclinical and clinical development operations, entered into multiple license and collaboration agreements for its Harbour Mice, and established an innovative therapeutic pipeline based on internal discovery and in licensing activities. In early 2018 Harbour raised an A+ Round from CDH and AdvanTech to support its in-licensed clinical programs for Greater China. Harbour’s development programs include:
  • An anti-FcRn based antibody against multiple autoimmune diseases, including myasthenia gravis and neuromyelitis optica, and a biologic against inflammatory dry-eye disease, among other potential indications. Harbour, which in-licensed these assets in 2017, is developing them for the Greater China market. Harbour recently filed two INDs for three different indications in China to conduct clinical trials with these assets.
  • A CD3-based bi-specific antibody therapy against Her-2 overexpressed cancer in clinical development, acquired in August 2018, which Harbour is developing for the Greater China market.
  • A clinical stage, anti-PD-L1 antibody for the treatment of multiple solid tumors and hematological cancers, acquired in August 2018, that Harbour is developing worldwide outside of China.
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Generic versions of EpiPen may ease a national shortage


The EpiPen shortage facing the country has worsened in recent weeks, but a Watertown, NY pharmacy has found a way around it.
Bolton’s Pharmacy, with locations on Main and Washington streets, has been using generic epinephrine auto-injectors for its prescriptions.
Supervising pharmacist Shawn M. Signor said the only real difference is the name brand. While the formulas vary, the results and functionality are practically the same.
“We have been frequently dispensing alternative versions of EpiPens for patients,” Mr. Signor said. “There is no backstock on them, so we haven’t had any trouble having them supplied at our pharmacy.”
By comparison, EpiPen is the trademark Pfizer associated with the product, just like Kleenex is associated with a facial tissue — it doesn’t mean the other versions aren’t effective.
Until the shortage is over, this may be the best option for consumers to consider.
The shortage
The limited availability is related to both pharmacy-level supply disruptions and manufacturing constraints, Pfizer stated in a recent release.
Sales of the EpiPens also spike during back-to-school season, as parents attempt to refill expiring prescriptions to keep in children’s backpacks, at school and at home.
Pharmaceutical company Mylan stated it’s “expediting shipments upon receipt from Pfizer” and that officials “are working closely with Pfizer to stay informed of anticipated shipments and are maintaining a regular dialogue with health authorizers to provide frequent updates on supply status.”
Expanded expiration dates
On Tuesday, the U.S. Food and Drug Administration said people can use some expired EpiPens for a few months longer, to help cover spot shortages. This can only be applied to EpiPens and its authorized generic version.
Certain batches of the devices, which inject lifesaving medication to stop severe allergic reactions, can be used for four months beyond their expiration, the FDA said.
“We are doing everything we can to help mitigate shortages of these products, especially ahead of the back-to-school season,” the FDA’s Dr. Janet Woodcock stated. “We’ve completed the necessary reviews of the data to extend the expiration date by four months for specific lots of EpiPen that are expired or close to expiring.”
Combatting the problem
On Aug. 16, federal regulators approved the first generic version of EpiPen, developed by Teva Pharmaceuticals. This version will be interchangeable with the original epinephrine auto-injector sold by Mylan. Pharmacists will soon be able to substitute this version when doctors prescribe the original EpiPen, but it’s not available yet.
This version may not launch in time for families urgently searching for supply now, so Mylan is encouraging patients to call its customer relations department at 800-796-9526 for help locating alternative pharmacies.
Alternative options include changing to a generic epinephrine auto-injector that is not the same formula as an EpiPen.
If a patient is interested in a generic version, they should talk with a health care provider about different options.
Also, be sure the prescription states “epinephrine auto-injector” instead of “EpiPen.” If not, pharmacies may not be able to provide the available alternative.
What is an EpiPen?
EpiPen refers to the brand-name version of an epinephrine auto-injector, which injects epinephrine, a chemical that narrows blood vessels and opens airways in the lungs. The pen is a quick self-injection system that can be used by anyone to deliver medicine to someone in allergic shock, or anaphylaxis.
Typical allergic reactions to treat with an EpiPen include insect stings or bites, food, drugs and other allergens, according to the American Academy of Allergy Asthma and Immunology.
The EpiPen is marketed by Mylan and manufactured by Pfizer. Other companies have made different types of epinephrine auto-injectors, most common being Adrenaclick and Auvi-Q, and can vary drastically in price. A consumer who switches from EpiPen to a generic auto-injector could be saving up to $430 per prescription.
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Natural Grocers Shrug Off Amazon-Whole Foods Threat


When Amazon.com Inc. bought Whole Foods last year, Kemper Isely worried about how his regional health-food chain would compete with the e-commerce giant.
A year later, the chief executive of Natural Grocers by Vitamin Cottage Inc. is sleeping better. Sales are up, shares have nearly doubled since January and the Colorado-based company is expanding its network of 147 stores.
Executives at many natural and specialty chains who expected Whole Foods under Amazon ownership to hurt their businesses have seen growth instead. One year after Amazon’s $13.7 billion takeover of the natural-foods pioneer closed on Aug. 28, sales at Sprouts Farmers Market Inc., Natural Grocers and hundreds of other health-food stores are up in dollar and unit terms from a year ago, according to retail-data firm Spins.
“Our growth rate has doubled since the Amazon transaction,” said Nicholas Green, co-founder and chief executive of Thrive Market, a natural and organic online grocery site.
Some natural grocers lowered prices after Amazon slashed the price of staples such as organic produce. Some said they have always kept their prices a notch below those at Whole Foods.
“We’ve been hyper-focused on price,” said Ben Friedland, vice president of marketing at Lucky’s Market, a 31-store natural food chain based in Colorado. Kroger Co. invested in Lucky’s in 2016 to expand its health-food reach.
Mr. Friedland, who previously worked for Whole Foods, said the Amazon deal spurred Lucky’s to speed up its rollout of online ordering, and sales haven’t suffered.
Some natural grocers said they have attracted new customers in the past year because of better service and more local products. At the same time, they said, Whole Foods stores have become more mainstream.
“After they put their blue signs all over everything and started selling Amazon Echos, it really kicked in that this is no longer this specialty, healthy chain,” said Tony Antoci, chief executive of California’s Erewhon Market, where same-store sales are up more than 20% from a year ago.
Lucky’s recently hired a manager to help in recruiting local brands. Thrive Market is signing more deals with suppliers to sell their products exclusively. Some of those food makers were unhappy that Whole Foods centralized purchasing and raised supplier fees, Mr. Green said.
Jimmy Stewart, co-owner of Stewart Brothers Inc., an Oregon-based juice company, has lost shelf space recently to bigger brands at Whole Foods and is sending more juice to independent natural grocers and conventional chains instead.
“They left us in the dust,” said Mr. Stewart, whose family company has sold products at Whole Foods for 20 years.
Spokeswomen for Amazon and Whole Foods declined to comment.
Whole Foods rivals have had to sacrifice margins to keep up on pricing, staffing and convenience. Some have used savings from federal tax cuts to fund the effort. Analysts remain concerned about how they will continue to fund the efforts.
“We have been and remain cautious on the bottom line uncertainty within food retail given ever-increasing competition,” said Vincent Sinisi, Morgan Stanley Equity Research Analyst.
Foot traffic at Whole Foods stores was up 8% in June and July compared with those months last year, before Amazon took over, according to data firm inMarket. Amazon reported $4.3 billion in physical store sales during its latest quarter, mostly at Whole Foods. That was up from the $3.7 billion in sales for the same period last year when the chain was a stand-alone company.
Amazon has added discounts and delivery at Whole Foods stores for Prime members. A pricing study by Morgan Stanley earlier this month found the price for a basket of items at Whole Foods was the second lowest since the survey began in 2014.
Some shoppers say they don’t like the new feel at Whole Foods. “Except for an occasional sale on tomatoes and avocados, so far there’s hardly a positive,” said Vik Puri, a 56-year-old nonprofit founder who switched from shopping at Whole Foods to Seattle Metropolitan Market, a local chain.
Some believe Whole Foods is stocking more conventional brands in products like cereal and beer and displaying them more prominently.
Whole Foods executives have previously said that its centralization push is helping the chain become more efficient and promote products better, and the company still works with local suppliers in getting their goods on shelves.
Grocery shares plunged last summer after Amazon said in June that it would buy Whole Foods. Stocks for six large food retailers including Kroger and Walmart Inc., lost around $12 billion in value. Some investors saw an opportunity.
“There is a world where retailers and manufacturers can co-exist with Amazon,” said Jacob Gamerman, senior research analyst for Neuberger Berman Group LLC, the asset-management firm that took an activist position in Whole Foods last year. One of the firm’s funds built up a stake in Kroger after the Amazon-Whole Foods deal was announced.
A year later, Kroger’s shares are up around 20%. Sprouts shares are up roughly 20%, and Natural Grocers shares have climbed by around two-thirds.
Many analysts said prospects are uncertain for grocers competing with Amazon and deep discounters. Since the Whole Foods deal, grocery executives mentioned the chain twice as often on average during earnings calls compared with calls in the months before, financial data firm Sentieo Inc. found.
Trader Joe’s and Aldi, fast-growing chains that sell natural and organic goods at a discount, have posted strong sales growth since the deal, according to an analysis of anonymized consumer credit- and debit-card transactions.
Tony Olson, chief executive of the Spins research firm, said that health-food stores that innovate will remain competitive, but the sector will continue to face challenges, given that many players are smaller and face rising costs.
“We will have the same worries,” said Natural Grocers’ Mr. Isely, who estimated that 60% of his company’s stores were near a Whole Foods location.
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Terminal Cancer: Putting Numbers to Caregiving’s Emotional Toll


More than 80% of caregivers for patients with terminal cancer exhibited clinically significant psychological distress, a British survey showed.
Survey responses from 1,500 adult caregivers showed that 83% had clinically significant psychological morbidity, as defined by scores on a validated general health questionnaire. Across all age groups, the rates of distress were five to seven times higher as compared with estimates for the general population.
Respondents also had worse general health status as compared with the general population, Gunn Grande, PhD, of the University of Manchester in England, and co-authors concluded in their study in Palliative Medicine.
“We were aware that carers’ psychological health suffers when caring for the terminally ill, but we were surprised at the sheer scale of the problem,” Grande said in a statement. “We found that the vast majority of carers suffered psychological morbidity at a level where further clinical investigation is recommended and where, for instance, their ability to concentrate, make decisions, and deal with problems may be affected.”
The study reinforces a large existing volume of existing evidence that caring for terminally ill patients imposes a heavy psychological toll on caregivers, said Lidia Schapira, MD, of Stanford Health Care in California
“It’s not a ground-breaking study, but it does add data to the field that’s emerging to document the suffering of caregivers,” said Schapira, who is also editor in chief of the American Society of Clinical Oncology’s Cancer.Net patient information site.
The findings represented responses from fewer than 30% of caregivers who received the questionnaire, raising questions about how representative the study population might be with respect to caregivers in the United States, she noted. Additionally, the caregivers were contacted following the death of a relative with cancer, complicating efforts to separate the distress associated with caregiving from that associated with bereavement.
Despite those limitations, the study “is a serious effort to capture the effects, the repercussions associated with caregiving for terminally ill patients,” said Schapira.
Grande and co-authors acknowledged recognition of the adverse impact of caring for terminally ill patients on caregivers’ own health. The objective of the study was to provide information about the magnitude of the adverse effect, which previous studies failed to capture, the team explained.
Prior studies often included results for specific types of psychological conditions, such as anxiety or depression, although reported rates were higher as compared with the general population. Others assessed overall psychological morbidity but did not include population-level data, used nonstandard assessment tools, or did not capture caregivers’ distress during the end-of-life period.
The investigators mailed survey materials to 5,271 adults in England who registered relatives who died of cancer during the first 2 weeks of May 2015. The materials included the General Health Questionnaire-12 (GHQ-12, psychological health) and the EuroQoL EQ-Visual Analog Scale (general health status) questionnaires. The surveys were sent 4 weeks after the death of the relative and focused on the health status of the caregivers during the last 3 months of the relatives’ lives.
Subsequently, 1,504 (28.5%) caregivers responded to the request for information. For comparison, the authors used data from a contemporary national health survey involving 6,500-6,800 residents of England.
The data showed that 83% of the survey respondents had significant psychological morbidity, defined as a GHQ-12 score ≥4. That contrasted with 15% of the general population. Across age groups from 18-24 to ≥75, the prevalence of significant psychological distress was five to seven times higher among the caregivers than among the general population.
The median GHQ-12 score across age groups was 6-8 for the caregivers (4 indicates “caseness,” or a need for follow-up) as compared with 0 in the general population. Women caregivers had higher scores than men did. The proportion of caregivers who met the criteria for caseness varied from 90% for those ages 25-54 to 80% for older groups. Caseness rates in the general population ranged from 11% to 17%. Women had higher scores than men.
Caregivers had lower general health scores (median of 75 versus 80 for the general population). Younger caregivers had lower scores than did their older counterparts.
“This study found far higher prevalence of psychological morbidity among carers during end-of-life caregiving than indicated by previous research, with clinically significant morbidity being the norm,” the authors concluded.
“This represents a large, hitherto unrecognized public health burden, the consequences of which need to be further established. If results are representative of end-of-life carers in England in general, over 400,000 of the estimated half a million end-of-life carers per annum may be at risk for substantial psychological morbidity, with effects likely to carry on into bereavement.”
Grande and co-authors reported having no relevant relationships with industry.
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Weight-Loss Drug Clears Major Cardiovascular Obstacle


Longer-term use of the weight-loss drug lorcaserin (Belviq) revealed no excess major adverse cardiovascular event risk, results of the CAMELLIA-TIMI-61 postmarketing trial found.
At a median of 3.3 years follow-up, there was no difference in major CV events — a composite of stroke, MI, or death — between the two study arms, occurring in 6.1% of lorcaserin-treated patients compared with 6.2% among those on placebo (HR 0.99, 95% CI 0.85-1.14, P<0.001 for non-inferiority), reported investigators led by Erin Bohula, MD, DPhil, of Brigham and Women’s Hospital in Boston.
Various cardiovascular outcomes among the 12,000 randomized patients were similar across the board, with none significant: cardiovascular death (1.5% with lorcaserin vs 1.4% with placebo), MI (3.8% vs 3.8%), stroke (1.4% vs 1.6%), heart failure (2.4% vs 2.5%), unstable angina (1.5% vs 1.3%), and coronary revascularization (6.8% vs 6.9%).
A key secondary outcome was new-onset diabetes for participants with prediabetes at baseline, which at the end of trial was diagnosed in 8.5% of lorcaserin-treated patients versus 10.3% of those on placebo (HR 0.81, 95% CI 0.66-0.99).
“Lorcaserin is the first pharmacologic weight-loss agent with proven cardiovascular safety for major adverse cardiac and vascular events, supporting its role as an adjunct to lifestyle modification for long-term weight management,” said Bohula during a press briefing here, “even in patients who are at particularly high cardiovascular risk.”
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Erin Bohula, MD, DPhil, presenting the results
The study was presented at the European Society of Cardiology (ESC) meeting and published simultaneously in the New England Journal of Medicine.
While adverse events of special interest were rare and similar between the two arms, there was a higher incidence of serious hypoglycemia among lorcaserin-treated patients — 13 versus four cases with placebo, mostly occurring in those with diabetes at baseline (P=0.04).
There was a non-significant increase in suicidal behavior or ideation in the lorcaserin group (0.4% versus 0.2% in placebo group, P=0.08) that appeared to be tied to patients who had depression before entering the trial. There were no deaths by suicide in the trial.
And while there were imbalances in both pulmonary hypertension (1.6% vs 1.0%) and FDA-defined valvulopathy (1.8% versus 1.3%) — both numerically higher with lorcaserin — the findings were not significant.
“Clinical experience with the first generation of anti-obesity drugs was not encouraging, despite successful weight loss, because of side effects, both on and off target,” wrote Julie R. Ingelfinger, MD, of Tufts University School of Medicine in Boston, and Clifford J. Rosen, MD, of the Maine Medical Center Research Institute in Scarborough, in an accompanying editorial. “In particular, agents with a serotonin-agonist mechanism of action, such as dexfenfluramine and fenfluramine, stimulated 5-hydroxytryptamine 2B (5-HT2B) serotonin receptors, which led to pulmonary hypertension and heart-valve problems.”
In September 1997, the FDA pulled fenfluramine-phentermine, “Fen-Phen,” from the market, roughly 6 months after its approval due to increased risk of symptomatic valvular heart disease. From 1999 to 2012, the agency blocked all weight-loss drugs from hitting the market.
In 2010, sibutramine (Meridia) was also pulled from the market due to an increase in the risk of stroke and MI. But an industry push starting that same year — which included over $60 million in lobbying — helped open the doors for new weight-loss drugs, and for some that had previously been rejected by the FDA. In 2012, lorcaserin became the first FDA-approved drug for weight-loss in over a decade. As lorcaserin binds to 5-HT2C receptors, concern remained over its cardiovascular safety.
“The use in general of weight-loss agents is fairly low in the U.S., and I think that speaks to the historical experience with weight-loss agents,” said Bohula. “I suspect there may be physicians and patients who are more inclined to use this pharmacologic agent going forward, in light of the safety profile.”
From 2014 to 2015, the CAMELLIA-TIMI 61 trial recruited and randomized patients who were overweight or obese to either 10-mg twice daily lorcaserin or placebo. All patients in the trial also had access to a weight-management program and unlimited telephone access with a dietitian.
In terms of weight control, treatment with lorcaserin resulted in ≥5% weight loss in 38.7% of lorcaserin-treated patients compared with 17.4% of those who received placebo (OR 3.01, 95% CI, 2.74-3.30, P<0.001). And ≥10% weight loss occurred in 14.6% of lorcaserin-treated patients compared with 4.8% of those on placebo (P<0.001).
In their editorial, however, Ingelfinger and Rosen expressed skepticism about the drug’s wider use. “With respect to efficacy, liraglutide would provide a similar degree of weight loss but a lower risk of diabetes,” they noted. “Thus, whether this trial will lead to enhanced utilization of lorcaserin by providers is uncertain, as is the ultimate role of this drug in the treatment of patients who are overweight or obese.”
The study was funded by Eisai.
Bohula disclosed relevant relationships with Servier, Merck, Lexicon, Paradigm, Novartis, Amgen, and AstraZeneca.
Ingelfinger and Rosen are editors with the New England Journal of Medicine.
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Questions Remain about Shingrix Safety with Autoimmune Conditions


The efficacy and safety of the new zoster vaccine Shingrix has not been established among patients with autoimmune diseases, researchers reported here.
Clinical trials of the vaccine in adults ages ≥50 in the ZOE-50 trial, and ages ≥70 in the ZOE-70 trial showed very strong efficacy — about 97%, compared with 40% to 50% for the older Zostavax vaccine. In the ZOE-50 study, 15,000 adults were randomized to the vaccine or placebo and followed for slightly over 3 years. During that time, there were six cases of shingles in the active treatment group compared with 210 cases in the placebo group.
In ZOE-70, which included 14,000 participants, there were 23 cases of shingles in this high-risk age group who received the active vaccine compared with 223 who were given placebo. Both studies were published in the New England Journal of Medicine and the vaccine was approved for use in the United States in October 2017.
“This is a really, really good vaccine,” said Elizabeth Kirchner, MSN, CNP, from the Cleveland Clinic at the Ohio Association of Rheumatology (OAR) annual meeting.
“But the problem is that patients with immune-mediated inflammatory diseases such as rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and lupus were all excluded from those trials,” she said.
Of particular concern is the adjuvant that was used in Shingrix, which has not been used before in humans.
“Adjuvants help the vaccine work. It’s been known even since the smallpox vaccine was used that if you added an irritant, a little lye or soap, it worked better. For about 100 years the only adjuvant we had was alum, but now we have several more,” Kirchner said.
The adjuvant used in Shingrix is an extract of the Quillaja saponaria tree native to Chile, which is a totally novel adjuvant that is unlike any previously used in vaccines, said Kevin Winthrop, MD, of the Oregon Health and Science University in Portland. “The efficacy of this vaccine is off the charts. No one has ever seen efficacy like this, and it’s probably because of the adjuvant,” he said at OAR.
The adjuvant is associated with significant reactogenicity, however, with up to 15% to 16% of patients having grade 3 systemic adverse events such as fever, myalgias, and flu-like symptoms that typically last for 2 days. “The worry is that this is going to cause flares in patients with lupus,” he said.
“We know that adjuvants kick up the immune system, get the innate immune system going. But I’m not so excited about kicking up the immune system in a patient with lupus and not knowing what it’s going to do to that patient’s disease,” Kirchner said.
This vaccine has been studied in HIV patients, cancer patients, and transplantation patients, and the patients did fine, she said. “But our concern is kicking up the immune system in autoimmune patients who already have a overactive immune system,” she said.
Shingrix was given preference over the previous vaccine Zostavax by the FDA, but the vote among the Advisory Committee on Immunization Practices was only 8 to 7 in favor, Winthrop said. “This was hotly debated. One reason was a lot of people had concerns about the adjuvant. They were worried that if you give a preferential recommendation, physicians will start using it in subpopulations [such as autoimmune patients],” he said.
“There also have been concerns about creating autoimmune diseases over the long term. In the ZOE trials, patients were only followed for a few years,” he said.
Careful postmarketing surveillance will be needed to ensure safety, he concluded.
Winthrop disclosed relevant relationships with AbbVie, Bristol-Myers Squibb, Galapagos, Lilly, Pfizer, and UCB.
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