The pharmaceutical industry has yet to discover how nitrosamines occur in its drugs and how to mitigate the risk of that happening.
If you had bacon for breakfast, you may have ingested some nitrosamines, the organic compounds that were also found in Sanofi's Zantac and spurred a recall of the blockbuster heartburn treatment four years ago. The recall created an opportunity for legal action by patients who had been taking the drug, and the first court case is set to begin in February 2023 in California.
Consequently, the industry has been challenged with how to discover how nitrosamines occur in its drugs and how to mitigate the risk of that happening. The FDA has issued guidance on allowable amounts in drugs, and physician and patients look to find alternative treatment, if necessary. All three stakeholders are trying to assess the risk of getting cancer from the nitrosamines, and recent studies have shown the risk to be relatively low. According to the FDA, nitrosamines are common in water and foods, including cured and grilled meats, dairy products and vegetables. Everyone is exposed to some level of nitrosamines.
Zantac Trial Impact
In the case of Zantac, more than 3,100 plaintiffs have filed suits against Sanofi, claiming that the company didn't warn of the potential danger of nitrosamines in the drug. According to a recent Bloomberg report, the company is at risk of losing a ton of money; trial judgments against Sanofi could reach $45 billion. Sanofi has repeatedly denied any liability and analysts have stated they are doubtful the plaintiff's case has merit.
"Since 2019, the medical, scientific, and regulatory communities have extensively evaluated the safety of Zantac’s active ingredient ranitidine, and the data shows there is no evidence of consumer harm from real-world use of Zantac," Sanofi said in a recent press release.
In the Bloomberg report, George Gray, professor at George Washington University who specializes in health-related risk analysis, says, “It really is hard to say just how big the risk of these medications might be especially given the benefit they might confer on people.”
Sanofi's statement helped correct its stock price, which fell on the news of the lawsuit.
Both FDA and the European Medicines Agency evaluated the available data and found no evidence that Zantac causes cancer. FDA, in collaboration with regulatory counterparts around the world, has set internationally recognized acceptable daily intake limits for nitrosamines. If drugs contain levels of nitrosamines above the acceptable daily intake limits, FDA recommends these drugs be recalled by the manufacturer as appropriate.
"Nitrosamine impurities may increase the risk of cancer if people are exposed to them above acceptable levels and over long periods of time, but a person taking a drug that contains nitrosamines at-or-below the acceptable daily intake limits every day for 70 years is not expected to have an increased risk of cancer," the FDA states.
Since the recalls and FDA's tightened regulation, the industry is still struggling with how to identify all the causes that create nitrosamine in medications and to prevent it from happening.
Where and when the impurities may occur is a complicated problem caused by numerable factors, ranging from something as straightforward as material used in blister packs to chemical interactions that occur before, during and after the drug making process.
Impact on physicians and patients
The FDA has offered guidance to physicians and patients, recommending physicians continue to prescribe medications when clinically appropriate and educate patients about alternative treatment options. Both pharmacists and prescribers may be able to dispense the same medication from a manufacturing lot that has not been recalled. Patients can find medications that have been recalled due to potential nitrosamine impurities on the FDA recalls webpage.
The massive infusion puts Verily in a good deal-making position as the health-tech arena grows.
Verily Life Sciences plans to use its newest $1 billion investment round, led by its parent company, Alphabet, to support expanding its focus on precision health, which includes initiatives in real world evidence generation, healthcare data platforms, and research and care. The company will also invest in strategic partnerships, global business development and potential acquisitions.
This whopper of an infusion puts Verily in a good deal-making position as the health-tech arena grows, as well as helps support its newer efforts in data platforms and research and technology that aim to make healthcare more individualized.
In March, president and chief operating officer Stephen Gillett outlined Verily's new strategy in the company blog. "Our new purpose is to bring the promise of precision health to everyone, every day. That purpose unites our work across the company now and captures where we are headed in this next phase of our company’s growth."
Analysts have compared Verily's funding to that of tech company Amazon buying One Medical – both strategies increase each companies' footprint in the healthcare technology market. Amazon acquired One Medical, a primary care provider that leverages in-person, digital and virtual interactions in its services, in a deal valued at $3.9 billion.
Recently, Verily has committed to working in biomedical research to virtual care, wearables and even technology for mosquito eradication. Verily has recently experimented with diabetes-detecting contact lenses, and care solutions for sleep apnea. Throughout the COVID-19 pandemic, the company also shifted its focus to COVID screening, testing and research programs. It developed one of the first community-based testing services, the Baseline COVID-19 Testing Program - which to date has tested nearly 2.5 million people. Using the Baseline Platform, the company has contributed to the HERO-Together study, which evaluates the Pfizer-BioNTech COVID-19 vaccine for frontline health workers.
Staff Changes
At this time, Verily is also shifting its top leadership. According to the company, the new "roles are the result of thoughtful succession planning led by Conrad and the board and in recognition of the skills and experience required to lead Verily as it becomes a more operationally and commercially focused company executing on its precision health strategy.”
Long-serving CEO Andy Conrad will become executive chairman of the Verily Board and current president Stephen Gillett will advance to CEO, with both changes effective January 2023.
Gillett joined Verily from Google in 2020 as an operational advisor to the company and to lead Verily’s effort to establish a Cybersecurity Center of Excellence. In November of that year, he was named Chief Operating Officer. Before joining Verily, Gillett was co-founder and CEO of Chronicle, an Alphabet cybersecurity company that is now part of Google Cloud.
Former FDA Principal Deputy Commissioner, Amy Abernathy, stated on LinkedIn and Twitter, "Sharing big congrats to Stephen Gillett, who will step into the role of CEO, and deep gratitude to Andy Conrad, who will move into the role of Executive Chairman." As president of Verily’s Clinical Studies Platforms, Abernathy says, "[Andy's] vision for Verily continues to fuel our momentum, and we are positioned for great progress ahead."
David Fajgenbaum and Grant Mitchell unveil Every Cure at Clinton Global Initiative.
The organization, Every Cure, is cofounded with Grant W Mitchell, MD, MBA and Tracey Dikora to create a novel end-to-end approach for identifying promising drug repurposing opportunities, by performing clinical trials that definitively demonstrate whether the drugs will work or not, and then working with disease organizations to ensure that they're used in the right patients, Mitchell tells Health Leaders.
Prior to Every Cure, Mitchell led a team at McKinsey & Co. to mine medical records and real-world data in pursuit of new uses for drugs. Dikora has studied repurposed drugs in rare diseases, including Niemann Pick C, MPS I, Familial Hypercholesterolemia, and others.
The launch was announced at the Clinton Global Initiative, a meeting of global leaders to create and implement solutions to the world's most pressing challenges brought together by the Clinton Foundation.
"We already have the tools we need to find new cures to deadly diseases," former president Bill Clinton said in a statement about Every Cure. "We just have to connect the dots between the research and the drugs available."
And that is just what Every Cure is all about. It plans to raise $55 million to fund its mission, which includes coordinating drug data, identifying generics that might offer hope for patients with a rare disease and bring the most promising drugs to clinical trials. The org says it is taking responsibility for making sure all appropriate drugs are fully tested for other diseases they can help treat, since no other agency, company or person is being held accountable for this concept. The nonprofit will create a central database on all the work being done in this space and make it available to all. Every Cure has already begun developing an algorithm to help identify possible other uses for existing drugs that they will then test in clinical trials. In an initial pilot, it has already identified 106 drugs that might treat 147 of the 9,000 rare diseases.
"Repurposing existing drugs is the fastest and cheapest way to treat diseases with the greatest return on investment for saving lives," Mitchell says. "Systemic barriers impede repurposing, so patients suffer while potential treatments are not fully utilized. Every Cure overcomes these barriers to systematically identify and advance promising repurposing opportunities and save lives."
There are many pharmaceutical companies using drug repurposing to build pipelines, and some of the more notable ones have been discovered by accident, such as sildenafil citrate, which failed in clinical trials as a high blood pressure treatment but became world renown as Viagra to treat erectile dysfunction. It has also been found to benefit children with a rare form of lung disease.
Instead of creating new indications for drugs through serendipity, Every Cure believes there needs to be a correlated and strategic effort within the industry to identify the most promising drug repurposing opportunities and bring them to patients, saving lives and costs.
"Our mission is to scale our efforts to all drugs and all diseases so that no patient has to needlessly suffer when a cure is hiding in plain sight," Mitchell says.
David Fajgenbaum, MD, MBA, MSc is the author of Chasing My Cure: A Doctor's Race to Turn Hope into Action; Assistant Professor of Medicine, Translational Medicine & Human Genetics, University of Pennsylvania; Founding Director, Center for Cytokine Storm Treatment & Laboratory; Associate Director, Patient Impact, Orphan Disease Center, University of Pennsylvania; Co-Founder & President, Castleman Disease Collaborative Network.
The effects of the SCOTUS Dobbs ruling are being felt across the industry.
The overturning of Roe vs. Wade rocked the nation and the industry back in June; so much so that more than 100 women leaders in biotech signed an open letter in response to the court's decision in Dobbs v. Jackson Women’s Health.
The letter expressed the signees' disappointment and outrage with the ruling and added that the Supreme Court ignored the "fundamental rights as women to make personal reproductive health choices and for clinicians to practice evidence-based medicine without fear of reprisal."
Everyone who has a stake in reproductive health— hospitals, physicians, patients and pharma-- are trying to determine the most appropriate way to move forward with women's healthcare.
“We expect that [the] decision will have practical impacts on hospitals and health systems, including on healthcare provided across state lines, EMTALA obligations, maternal health care, the clinician-patient relationship, medical education and access to care for individuals regardless of socioeconomic status," American Hospital Association's General Counsel, Melinda Hatton, said in a June statement. "We are committed to helping our member hospitals and health systems navigate the evolving landscape consistent with AHA’s mission of advancing the health of all individuals and communities.”
AHA declined to provide any additional statements.
Hospitals may find themselves in a precarious situation now that abortion is illegal in some states under certain circumstances. If they follow their previous policies around standards of care, they could break the law. If they follow the new law, they could put some patients' lives in danger. In combination with the risk of medical liability, hospitals now need to be concerned with criminal liability, which is a heavy burden being imposed on them very quickly.
Heather Woolwine, director, public affairs, media relations and presidential communications at MUSC in South Carolina said in accordance with the new law, the hospital's focus will remain on the health of both mother and baby. "When complications arise during a pregnancy, our providers are medically and ethically obligated to explain all options to their patients. MUSC and its care providers will continue to provide the most appropriate and safest care possible while complying with South Carolina law," she said.
The Reproductive Health Access Project, which trains, supports, and mobilizes primary care clinicians to ensure equitable access to sexual and reproductive healthcare, including abortion, says states where abortion is still legal have experienced an "unprecedented rise" in patients who have traveled out of state to seek care. "This increased demand has put enormous strain on existing abortion care providers," the group reports. The Project says it is currently working with more clinicians and health centers than it ever has before, to help fill a critical void in abortion access by providing abortion care in their communities.
"We are already hearing stories of hospitals and clinics having trouble determining how to administer appropriate medical care in light of the restrictions," Daré CEO Sabrina Johnson, one of the women who signed the biotech open letter, said. "As may be expected, most impacted is the provision of medical care to a woman who is pregnant, but the Roe vs. Wade reversal has also impacted the provision of care and counseling to women who are seeking highly effective forms of contraception in light of the reversal."
Johnson continued to note that clinicians have experienced an increase in requests from women seeking highly effective forms of contraception. Many of these women are in their early reproductive years but are requesting tubal ligation. In response clinicians and advocacy groups are working to provide sufficient education so that women understand all of their contraceptive choices, including highly effective reversible methods such as implants.
Men seem to also be changing their reproductive health choices as more younger males seek vasectomies since the ruling.A Massachusetts urologist reported an increase in men seeking vasectomies stemming from the court decision, both nationally and locally, in a Worcester Telegram news article. Mitchell Sokoloff, MD, professor and chair of the Department of Urology at UMass Chan Medical School and UMass Memorial Medical Center, said the increase includes younger men, "who aren’t normally interested in such a dramatic approach to birth control.”
Pharma can contribute
According to Terry Weber, CEO of Biote, this is the opportune time for the industry to increase its efforts on educating patients about the effectiveness of available contraceptives, long-acting reversible contraception, sterilization methods, and the potential healthcare benefits they provide to the patient. It is also time to focus on helping patients evaluate and find the birth control method that best fits their body.
"Information and education are the best ways to enable patients to feel empowered to seek and have confidence in their birth control methods," Weber says.
Debunking myths is a good first step to educating patients. For example, one significant barrier to contraceptive use could be a parent who believes that starting contraception will encourage promiscuity, will interfere with future fertility, or will cause breast cancer. "These myths need to be soundly addressed in the media, in schools and in our medical offices," Weber says.
"Sharing links, developing stories for the media like we are doing right now, giving out brochures and educational pamphlets that talk about common misconceptions, organizing talks in schools are all activities we should be doing to help educate and dispel these myths," she adds.
Several agencies and organizations are trying to bring forth better contraceptive education for patients and physicians. The U.S. Department of Health and Human Services launched the ReproductiveRights.gov public awareness website, which includes a patient fact sheet describing all patients' rights to reproductive care and access to insurance coverage as protected by law. Health insurers must provide coverage for contraceptive services at no cost as required by the Affordable Care Act.
Daré's Johnson says she believes the pharma/biotech industry can help ensure women are empowered to control their reproductive rights by ensuring access to accurate information about all of the contraceptive options available today, including clear information about correct usage and effectiveness.
"In addition, as an industry we can continue to invest in research and development of new contraceptive technologies so that we ensure there are more options available to women that better meet their lifestyle objectives," she says. "The best contraceptive for her is the one she can incorporate reliably into her routine."
AstraZeneca/Daiichi drug becomes first specifically approved for HER2 mutant NSCLC.
Enhertu (trastuzumab deruxtecan) became the darling of this summer's 2022 ASCO Annual meeting when its remarkable study results revealed the possibility of a new treatment option for patients with HER2-low breast cancer.
Investigator and presenter Shanu Modi, MD, of the Memorial Sloan Kettering Cancer Center, earned a standing ovation after her ASCO presentation on the phase 3 DESTINY-Breast04 trial.
Enhertu is the first HER2-directed therapy to demonstrate a survival benefit in this population, and these results hold the promise of changing the standard of care for patients with HER2-low breast cancer.
Continuing its winning streak this month, the antibody drug conjugate received accelerated approval to treat adult patients with unresectable or metastatic non-small cell lung cancer (NSCLC), making it the first drug specifically approved for HER2 mutant NSCLC.
"The availability of Enhertu as the first HER2 targeted treatment option for HER2 mutant non-small cell lung cancer is great news for patients," Upal Basu Roy, PhD, MPH, executive director of research at LUNGevity, says in a prepared statement. "We are thrilled to see a novel treatment option available that targets this group of rare mutations in lung cancer. This approval is a great reminder that access to high-quality biomarker testing will be critical to ensuring that patients whose tumors have HER2 mutations have access to these new therapies."
The approval was based on results from the DESTINY-Lung02 phase 2 trial. Patients with HER2 mutant unresectable or metastatic non-squamous NSCLC responded to the drug with a 57.7% objective response rate. In the trial, investigators evaluated the safety and efficacy of two doses of trastuzumab deruxtecan-nxki (5.4 mg/kg and 6.4 mg/kg) in 152 patients with HER2 mutant metastatic NSCLC with disease recurrence or progression during or after at least one regimen of prior anticancer therapy (including a platinum-based chemotherapy).
"HER2-mutant non-small cell lung cancer is an aggressive form of disease which commonly affects young patients who have faced limited treatment options and a poor prognosis to date," says Dave Fredrickson, executive vice president, oncology business unit at AstraZeneca, in the press release. This highlights the importance of testing for predictive markers, including HER2 in lung cancer, at the time of diagnosis to ensure patients receive the most appropriate treatment for their specific disease.
To that end, the FDA also cleared a companion diagnostic test, the Oncomine Dx Target Test by Thermo Fisher Scientific, to identify NCSLC patients who may be candidates for trastuzumab deruxtecan-nxki. The diagnostic test is designed to simultaneously evaluate 23 genes associated with NSCLC.
This marks the third indication for Enhertu to receive FDA approval. In May, Enhertu was approved in the U.S. for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer and again in early August as the first HER2-directed therapy for patients with HER2-low metastatic breast cancer.
Daiichi and AstraZeneca have been collaborating since 2019 to jointly develop and commercialize trastuzumab deruxtecan and according to the companies, "a comprehensive development program is underway across multiple HER2 targetable cancers, including breast, gastric, lung and colorectal cancers."
There's more to come from this exciting breakthrough drug.
Deloitte predicted this type of strategy from nontraditional players in its report, Increasing consumer engagement through retail pharmacy services.Deloitte reports that the increased attention on value-focused healthcare, combined with the primary care physician shortage, creates a perfect opportunity for retail pharmacies to disrupt the status quo.
"Fueled by healthcare reform, increasing competition, and shrinking margins, retailers are faced with the reality that their health and wellness business should consider adapting to the changing landscape," the report says.
And adapting is what CVS – and others, such as Amazon, Walmart and Walgreens – is doing, perhaps disrupting healthcare even more than the pharma and the healthcare industries themselves. During the Wednesday earnings call, which also reported an 11% increase in earnings year over year for the second quarter, CVS Health president and CEO, Karen Lynch, said the company's strategy of adding more health services has led to rising sales and deepening customer relationships.
CVS is also looking to boost its in-home care presence by acquiring Signify Health, a public, home health company featuring a value-based healthcare platform enabled by advanced analytics, technology and nationwide healthcare networks to provide more care at home. It has been reported that CVS was hoping to buy One Medical, but Amazon beat them to a deal. According to the Wall Street Journal, Signify is exploring strategic alternatives, including a sale, and CVS is expected to face competition from private equity firms and care providers in the bid for acquisition.
Why is this a threat?
For many years, CVS has been vowing to change the way U.S. healthcare is delivered, including reducing the need to visit a physician's office or be admitted to a hospital. Today, health market conditions and patient behavior are just two of the reasons that retailers are securing a foothold in the health services arena.
For example, Bain & Company's new study shows that innovative primary care models from nontraditional players will deliver more efficient care, improve patient outcomes and lower costs. Bringing new care and reimbursement models to the market along with a bigger focus on virtual care, these nontraditional players are gaining traction and have the potential to grab as much 30% of the U.S. primary care market by 2030, the new report says.
The study also says that retailers will grab market share with full-scope primary care and the big retail pharmacies could account for 5-10% of total primary care by 2030. Traditional fee-for-service will still be the predominant method of care in 2030, but it stands to lose 15-20% of market share to models that provide enhanced patient experiences, better physician experiences and more collaborative team-based care.
Beyond its nearly 10,000 brick-and-mortar drugstores, CVS, with a market value of $134 billion, owns Aetna insurance and pharmacy benefits manager CVS Caremark, and currently provides patient care at its MinuteClinics.
As a sign that it is planning to expand its efforts through technology, CVS hired its first senior technology role to focus on tech strategy and business growth, the company states. Tilak Mandadi, formerly chief strategy, innovation and technology officer at MGM Resorts, stepped into the role at the end of July as executive vice president, reporting directly to Lynch.
"Technology is a catalyst for value-creation and growth at CVS Health," Lynch says in a prepared statement about the new hire. "We're confident Tilak will drive these efforts as we prioritize serving consumers wherever and whenever they need healthcare."
This is just the beginning of an emerging mindset of major retailers that will continue to impact the primary care market and influence how pharma distributes its products, and to whom, in the future.
Biden's rebound is far from the first, although they are reportedly "rare."
Nothing like President Joe Biden having a rebound case of COVID-19 after taking the anti-viral Paxlovid by Pfizer to shine a light on the drug's effectiveness.
The President tested positive for COVID-19 for a second time right after being treated with Paxlovid for his first bout, the Associated Press reported. While the effectiveness of Paxlovid has come into question, some experts are saying that Biden's relapse is just a reminder that sometimes that's what happens when one sole anti-viral is chasing an ever-evolving virus.
Biden's rebound is far from the first, although they are reportedly "rare." Since the anti-viral got EU approval late in December, occurrences of rebound have been cited. Some medical experts are saying they may be more common than previously thought, The Washington Post reported.
A report in Science describes how easily a virus can learn to work around a single drug, and researchers expect Paxlovid will eventually lose its effectiveness as the virus mutates to thwart it. So far, no mutations have seemed to interfere with Paxlovid’s effectiveness, the Science report says, and scientists are still trying to determine why these rebounds are happening. But, they warned, "recent studies suggest the virus is poised to develop resistance—a fate that befalls many antiviral drugs."
Likewise, a University of California San Diego School of Medicine study published June 20, 2022 in Clinical Infectious Diseases suggests insufficient drug exposure is most likely the cause for a Paxlovid rebound, at least that was the case in one patient studied, as the patient did not show drug resistance or impaired immunity. The authors said the rebound of COVID-19 symptoms following treatment is likely due to not enough of the drug getting to infected cells to stop all viral replication. This leaves it up to the prescribing physician to determine the adequate drug protocol beyond the standard five days.
Also, Paxlovid is not meant for every patient with COVID-19 – only those at increased risk due to age, disease such as cancer, diabetes, hypertension, obesity, or being a former or current smoker, for example. In other words, according to Pfizer's own report, Paxlovid is not recommended for people who are unlikely to get seriously ill from COVID-19. To that point, the June, Pfizer discontinued a clinical trial for standard-risk people because Paxlovid didn’t significantly reduce hospitalization and death in that group.
In many patients, Paxlovid has shown positive results, not only keeping them from becoming very ill, but consequently, keeping them out of the hospital.
A new study by Epic Research calls Paxlovid a "game changer," as it found that patients prescribed Paxlovid are roughly five times less likely to be hospitalized and 10 times less likely to die than patients with COVID-19 who are not prescribed. Paxlovid prescriptions have increased throughout 2022, with a notable increase following the federal Test to Treat announcement in March 2022, Epic Research reports. The nationwide initiative was launched in March, giving individuals “One-Stop Test to Treat” sites at thousands of locations nationwide. In May, the program was expanded to include federally supported Test to Treat sites. According to Epic Research, the prescription rate peaked in May 2022 when 23% of patients with COVID-19 were prescribed Paxlovid.
According to study author Jeff Trinkl, MD, director of clinical informatics at Epic, one of the most surprising findings from the study is how drastic the difference in death rate is between those who were prescribed Paxlovid and those who were not. "While we expected a lower rate of hospitalization and death, the numbers were even greater than expected," he says. There were over 97,000 Paxlovid prescriptions during the study period in the Epic data set. This study evaluated any patient with a COVID diagnosis and/or positive test during the study period, December 1, 2021 – June 30, 2022. "We did not exclude patients who may be deemed to be at lower risk, but currently, Paxlovid has emergency use authorization for those at risk for severe COVID-19 illness, so it is likely the group prescribed Paxlovid is at greater risk for hospitalization and death than the general population," Finkl adds.
The anti-viral appears to be working well for Pfizer, as its second-quarter revenue and profit was largely driven by sales of its COVID-19 vaccine and Paxlovid. Pfizer booked $27.7 billion in revenue, a 47% increase over the same period last year and its largest quarterly sales on record. The pharmaceutical company reported $9.9 billion in net income, a 78% increase over the second quarter of 2021.
As the only biotech with an approved vaccine for monkeypox, can Bavarian keep up with demand?
On July 23, WHO voted to declare monkeypox a "public health emergency of international concern," the highest level of warning given by the agency. The risk of monkeypox is moderate globally, but in Europe, it is considered high, WHO reports. The designation is meant to initiate an international response and allow funding for collaborations on sharing vaccines and treatments. It also increases the need for more vaccines that are provided solely by Danish biotech Bavarian Nordic, and it appears demand is outstripping supply.
So far this year, there have been more than 16,000 cases of monkeypox in more than 75 countries, and five deaths in Africa. There are 2,592 U.S. monkeypox cases in the U.S., with New York, California, and Illinois among the states hit hardest, according to the most recent data from the Centers for Disease Control and Prevention (CDC).
Raj Panjabi, director of the White House pandemic preparedness office, said the WHO declaration was a "call to action for the world community to stop the spread of this virus" and a "coordinated, international response is essential" to stop the spread of the disease and protect communities at the greatest risk of contracting it. Efforts have been made to expand testing and access to vaccines, but case numbers have escalated rapidly in recent weeks.
The disease has been spreading chiefly in men who have sex with men in the recent outbreak, outside of Africa, where it is endemic. Countries in Africa have experienced sporadic monkeypox outbreaks since the virus was discovered in 1970. In Nigeria, an outbreak has existed since 2017.
However, the CDC has reported identifying infections in a small number (at least eight) of cisgender women and the first documentation of two cases in children just this month.
The virus is not a sexually transmitted disease but most often spreads through prolonged physical contact. It can spread by handling clothes or bedding used by an infected person or through respiratory droplets.
The current global outbreak of monkeypox virus infection in humans suggests changes in biologic aspects of the virus, changes in human behavior, or both; such changes might be driven by waning smallpox immunity, relaxation of COVID-19 prevention measures, resumption of international travel, and sexual interactions associated with large gatherings, according to a study in the New England Journal of Medicine.
EC approval and WHO alarm boosts demand
On Monday, July 25, the European Commission (EC) approved Bavarian Nordic’s Imvanex vaccine to be marketed as protection against monkeypox. Bavarian reported that the EC approval was speedy, taking only one month when normally the process takes six to nine months. The shot had already been approved by EC for a vaccine against smallpox in 2013.
On the news of the EC approval, Bavarian stock rose as much as 10% in Copenhagen trading, Bloomberg reports. The approval not only raised Bavarian's stock but also others who are working on a monkeypox vaccine, according to Seeking Alpha. These past few months, the biotech has raised its 2022 financial forecast several times and its estimate for full-year revenue is now more than double what it predicted earlier in the year. “With the recent upgrades of our financial guidance we have significantly improved our cash position and we are now even approaching a break-even EBITDA for 2022,” Paul Chaplin, president and CEO of Bavarian Nordic said in a prepared statement.
Keeping up with demand
Bavarian Nordic is also in talks to potentially expand production capacity. Bavarian has annual production capacity of 30 million doses, including the monkeypox vaccine and other vaccines it makes. It can meet current demand in the tens of millions of doses for the monkeypox vaccine, Chaplin said in an interview with Reuters.
The federal government plans to release more than 1.6 million doses of the monkeypox vaccine Jynneos by the end of the year, but demand is so high that the 56,000 doses released in June have almost all been used.
According to the Center for Infectious Disease Research, the vaccines are in very limited supply, with people from all over the United States reporting waiting in long lines only to be turned away from clinics, and experts say sufficient doses of the two-dose Jynneos vaccine likely won't be available for months or even years.
Recent reports from the CDC, Oregon, San Francisco, New Hampshire, New York, Chicago, Los Angeles, New York City, Minnesota, Florida, and Virginia all say that demand outstrips availability of the vaccine.
Bavarian is working with an unnamed U.S.-based contract manufacturer to expand its production capacity. Chaplin said he hoped that process would be completed later this year, and added the company was in early talks with others, including contract manufacturers and other vaccine makers, in case a further expansion is needed.
Earlier this month, U.S. Biomedical Advanced Research and Development Authority (BARDA), ordered an additional 2.5 million doses of liquid-frozen Jynneos, a non-replicating smallpox vaccine and the only FDA-approved vaccine against monkeypox. The new order follows two previous orders from BARDA in June and July 2022 for 500,000 and 2.5 million doses respectively which, together with an order from BARDA in 2020 for 1.4 million doses, will bring the total deliveries in 2022 and 2023 to nearly 7 million doses.
“Expanding our manufacturing capabilities into the United States allows Bavarian Nordic to deliver more monkeypox vaccines to meet the immediate worldwide demand for Jynneos," Chapin said in a prepared statement.
The Centers for Disease Control and Prevention (CDC) and the California Department of Public Health (CDPH) recommend that individuals aged 18 or older who are at highest risk of monkeypox infection get the shots. Current limited vaccine is being prioritized for individuals who have or may have been exposed to the monkeypox virus, or who are at high risk for occupational exposure. The vaccines will be distributed through a tier system, prioritizing areas with a high number of confirmed cases.
The CDPH further recommends first vaccinating persons at risk in the community with non-healthcare related exposures, as opposed to vaccinating healthcare workers. In healthcare facilities, current infection control recommendations (including use of PPE) should be followed.
The products treat diseases such as depression, anxiety, psychosis, alcohol dependence, myasthenia gravis and Parkinson disease.
European central nervous system (CNS) specialist Neuraxpharm, with 35 years of experience in CNS disorders, has agreed to buy two portfolios from pharma giant Sanofi. The purchase includes 17 molecules that represent 38 brands marketed in over 50 countries.
The products treat diseases such as depression, anxiety, psychosis, alcohol dependence, myasthenia gravis and Parkinson disease. The CNS portfolio includes Nozinan, Tranxene, Tiapridal, Dogmatil, and Largactil. The pain and vascular portfolio includes Topalgic and Trental.
"There is significant growth potential in the pharmaceutical sector, especially in the CNS market driven by an ageing population and an increasing awareness of mental health. This phenomenon is a global trend," Dr. Jörg-Thomas Dierks, CEO of Neuraxpharm, said in a prepared statement. "With the upcoming acquisition, we will not only strengthen our presence in Europe, but also lay the ground for further expanding our international presence."
The acquisition enables Neuraxpharm to bolster its position as a leading European specialty pharmaceutical company focused on CNS, and aligns with Sanofi CEO Paul Hudson’s streamlined product strategy launched in 2019. Sanofi calls the strategy a "play to win," which means divesting underperforming areas and focusing purposely on high performing products.
Following the acquisition, Neuraxpharm's annual gross sales could be around $600 million.
AbbVie quits one of two potential Alzheimer's treatments connected to Alector partnership.
In 2017, AbbVie and Alector joined together to develop and commercialize two therapeutics for Alzheimer’s. After a recent review of AL003, AbbVie has decided to abandon efforts for that drug, but will continue to pursue AL002, which is focused on targeting triggering receptors expressed on myeloid cells 2 (TREM2).
AL002 is an investigational, humanized monoclonal antibody whose role in potentially treating Alzheimer's was first identified in large-scale genome-wide association studies. Researchers found that reducing TREM2's functionality may contribute to AD progression and other types of dementia. By increasing TREM2 in the brain, there may be a way to target multiple pathologies linked to the disorder instead of just focusing on one pathology type.
The role of TREM2 in Alzheimer's treatment has been studied for many years. In 2021, AL002 became the first product candidate to reach Phase 2 clinical development that targets TREM2. Results from the INVOKE-2 Phase II clinical trial, which looked into the safety and efficacy of the drug in slowing disease progression in people living with Alzheimer's were positive.
Alector's novel approach -- immuno-neurology— to treating neurodegenerative diseases focuses on the immune system. In 2018, the company doubled down on this theory by tripling its workforce and expanding its facility, all with the expectation of taking five drugs into clinical trials.
The abandoned drug, AL-003, was designed to treat Alzheimer's using the body's immune system to fight the neurodegeneration. AL003 is a molecule designed to modulate checkpoint receptors on the brain’s immune cells, targeting sialic acid-binding Ig-like lectin 3 (SIGLEC 3, also called CD33).
The monoclonal antibody counteracts the function of Siglec-3, a microglial transmembrane receptor that reportedly interacts with TREM2. The gene encoding Siglec-3, CD33, has been associated with AD risk via a protective variant, expression levels, and alternative splicing.