PLAN AHEAD FOR THE 2020-2021 FLU SEASON

“Not getting a vaccine is like not wearing a mask”, said Dr. Randy Bergen, clinical lead for Kaiser Permanente Northern California flu vaccine program.

Depending on how well manufacturers of flu vaccines are able to predict which viral strains will be most prevalent in the upcoming season, a flu shot does not always guarantee full immunity. Even so, amid the COVID-19 pandemic, it is more important than ever to be vaccinated, especially in vulnerable populations. Vaccine manufacturers are expecting a 15% increase in vaccination rates compared to last year.

The "recurring mutations" of the influenza virus make it impossible to create a vaccine that will be effective against every strain of the flu. Each season's flu shot is composed of the most frequent strains isolated in the previous season. Studies show that vaccination reduces the risk of illness by 40% to 60% when the flu viruses circulating are well-matched to the vaccine, according to the CDC.

There are many different types of vaccines:

1)Trivalent vaccines, for those 65 years and older include:
    a)  Fluad
    b)  Fluzone High Dose
2) Quadrivalent vaccines, for those 6 months of age and older, include:
    a)  Afluria
    b)  Fluarix
    c)  Fulavel
    d)  Fluzone
3) Flucelvax, for ages 4 and up
4) Flublok, egg-free for those 18 years and up
5) Flumist, a Live Nasal vaccine, for ages 2 to 49

The CDC estimates that influenza has resulted in between 140,000 to 810,000 hospitalizations and between 12,000 to 61,000 deaths in the United States, annually since 2010. Fortunately, due to social distancing and mask-wearing this year, countries in the Southern Hemisphere that have their winter during the Northern Hemisphere’s summer, such as Argentina and New Zealand, have already seen an unprecedented drop in their flu cases in May and June.

The 2020-2021 vaccine should be widely available by September, though the CDC recommends that people get a flu vaccine by the end of October, because it takes two weeks for the immune system to develop antibodies and provide protection. (Flu season typically runs from late October through early April.) Getting vaccinated later can still be beneficial and vaccination should continue to be offered throughout the flu season, even into January or later. Getting vaccinated early (in July or August) is likely to be associated with diminished protection against flu infection later in the flu season, particularly among older adults.  Be sure to contact your physician or pharmacist for additional information.

https://www.cdc.gov/flu/prevent/keyfacts.htm

https://www.sfgate.com/news/article/Not-getting-a-flu-vaccine-is-like-not-wearing-15473514.php

https://www.usatoday.com/story/news/factcheck/2020/08/16/fact-check-flu-vaccine-hasnt-eradicated-virus-but-has-reduced-burden/3319252001/

https://www.usatoday.com/story/news/health/2020/08/17/covid-19-and-flu-season-the-overlap-could-overwhelm-hospitals/5582893002/

COVID-19 ANTIBODY VERSUS DIAGNOSTIC TESTING

One of the main challenges in response to the COVID-19 pandemic has been testing. Diagnostic tests can confirm if someone has an active COVID-19 disease, whereby antibody tests confirm if someone previously had the disease and has developed immunity. Numerous diagnostic tests have been developed to improve the accuracy, shorten the time required to produce results, and make the process to obtain a sample less invasive. Abbott has produced a diagnostic test that requires only 5 minutes and a sample from the nostril, which is faster and less obtrusive than previous tests obtained from nasopharyngeal samples. Diagnostic tests allow medical providers to make a differential diagnosis, recommend self-quarantine and pursue supportive care measures. Recent CDC statistics estimate nearly 5 million people have been tested for COVID-19 in the United States.

Another significant type of testing is serology testing. Dr. Redfield, the CDC Director, has said that these tests will be an essential part of the United States plan to move forward. The purpose of serological tests is to determine the presence of antibodies in the blood. Antibodies develop as part of an immune response to infection, as opposed to diagnostic testing which aims to detect the presence of a disease-causing agent, known as an antigen. Serological tests can provide insight into how many asymptomatic people have been previously exposed to the virus and have developed antibodies to fend off infection, and possibly prevent new infections. The presence of these antibodies may suggest people could return to work in a safe manner.

The National Institutes of Health (NIH) has launched a study utilizing antibody testing in over 10,000 people to quantify undetected cases of COVID-19. Quantifying asymptomatic cases and those that have immunity may shed light into the degree of virility and transmissibility of the virus. Therapeutically, serological tests may be utilized to determine who can donate blood that can be used to manufacture convalescent plasma as a possible treatment for critically ill patients with COVID-19.

Epidemiologists often reference “herd immunity” when discussing communicable diseases. Herd immunity is an indirect protection from infectious disease that occurs when a large percentage of a population has become immune to an infection. Thus, providing a measure of protection for individuals who are not immune. How contagious a virus is determines what percentage of people need to be immune to achieve herd immunity. To put it into context, measles requires a minimum of 92% of a population to be immune to prevent its spread. Laboratory data has indicated SARS-CoV-2 is not as contagious as measles. Thus, according to researchers at Johns Hopkins University, if 70% of a population is immune to COVID-19, herd immunity may be achieved.

There are still several questions that remain regarding antibodies and immunity against SARS-CoV-2. The length of immunity is unknown and may play a crucial role in establishing guidelines for reopening the economy, relaxing social distancing requirements, better understanding the immune response to the virus, and vaccine development. Length of immunity can vary widely as observed previously with other viral infections. For example, immunity to the common cold can be as short as a few months, while protective antibodies against the virus that caused the SARS outbreak in 2003 are still present in people almost two decades later. The length of immunity will help to model a potential vaccine schedule like an annual flu shot or a tetanus vaccine administered every ten years.

The immune system develops several different types of antibodies in response to an infection; however, it remains to be determined which antibodies should be the primary focus. IgM is typically the first antibody produced by the immune system, followed by IgG. Testing for IgM can indicate a more recent infection, while the presence of IgG may be a better indicator of sustained immunity. A potential area of concern is that if a person is tested shortly after coming in contact with the virus and has not yet had time to develop antibodies, test results may indicate a false negative. It is not currently known how long antibodies will remain present in the body after the infection has been resolved.

The FDA has authorized an expedited process for the many antibody tests in an effort to increase accessibility. Only four of the -more than 90 antibody tests now on the market in the U.S. have gone through vetting through the Emergency Use Authorization (EUA) process. The biggest concern is that tests may not have a high level of specificity; they may return false positives when someone has developed antibodies for other viruses. Due to the variables and current limitations of antibody tests, the FDA has issued recommendations to health care providers -not to use these antibody tests as the sole basis to diagnose COVID-19, but rather as information about possible prior exposure.

In the constantly evolving battle against COVID-19, serological tests will provide an essential tool for scientists and medical professionals as more data is compiled and tests become more refined.

https://www.medicinenet.com/what_antibody_testing_tells_us_about_covid-19-news.htm?ecd=mnl_day_042120

https://covidtracking.com/data/us-daily

https://www.medicinenet.com/coronavirus_herd_immunity_antibody_test_accuracy-news.htm?ecd=mnl_day_042420

https://www.healthline.com/health/serology

https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/testing.html

https://www.fiercebiotech.com/medtech/fda-officially-authorizes-its-first-serological-antibody-blood-test-for-covid-19

https://www.fda.gov/medical-devices/letters-health-care-providers/important-information-use-serological-antibody-tests-covid-19-letter-health-care-providers

Impact of Coronavirus on Prescriptions

During the Coronavirus pandemic insurance companies and pharmacy benefit managers have executed many allowances for prescriptions, including relaxation of “Refill too soon” edits, 60-day extension of existing prior authorizations, and allowing retail 90-day prescriptions. This could lead to increased costs.

However, as the entire medical community focuses on the COVID-19 pandemic, volumes of other types of medical visits and prescriptions have dropped dramatically. According to a survey taken by Piper Sandler, a financial services company located in Minneapolis, patient volumes are down 65% and may still be down by about 12% one year from now.

In addition, more than half of all office visits will be via telemedicine through the foreseeable future. Telehealth visits are expected to be as high as 54% of all visits, which is more than a 5-fold increase over pre-COVID-19 numbers. This will help some practices, but is still contributing to a furlough of some medical staffing.

Along with an unprecedented drop in patient volumes, prescription writing dropped by 47% in March, as patients refrain from normal office visits. It is expected to be down by a similar percentage in April. The number of prescriptions for some drugs have declined significantly, while others appear to be holding steady. Total prescriptions for drugs for acute use, such as headaches or heartburn, have plummeted by 28% since February. In contrast, chronic disease therapies, such as those for diabetes or mental health, are doing well, with weekly scripts even growing 2% at the end of March as compared with early February.

Vaccines saw the most decline, most likely because people are concerned about going to doctor offices and pharmacies for vaccinations to address viruses and diseases they do not even have. Other medications that have declined are ophthalmic preparations such as Restasis, and IBS-Constipation medications such as Linzess. Meanwhile, the autoimmune market, HIV and anticoagulants have so far not seen any changes.

Biopharma is not immune to this phenomenon.  The current lockdown is not only hurting clinical trial enrollment, but also delaying regulatory timelines for those drugs that are nearing an approval.  New drug marketing has also been affected because pharmaceutical representatives are unable to call on doctors due to COVID-19 social distancing and quarantine guidelines; for example, the launch of Bristol Myers Squibb's long-awaited Multiple Sclerosis drug, Zeposia, has been postponed.

The coronavirus impact as it relates to the pharmacy benefit is changing by the hour.  The PBIRx team of clinical pharmacists is constantly researching to keep our clients and partners abreast of the newest information so that they can make knowledgeable decisions.

https://www.healthcaredive.com/news/doctors-say-covid-19-has-slashed-patient-volumes-made-finances-shaky/575876/

https://www.fiercepharma.com/marketing/retail-scripts-vaccines-and-acute-drugs-decline-sharply-amid-covid-19

https://www.fiercepharma.com/marketing/biopharma-s-drug-launch-trajectory-bent-by-covid-19-but-some-maybe-more-resilient

COVID-19 Vaccine

Recent statistics in the United States reveal nearly 700,000 confirmed coronavirus cases and over 36,000 casualties. Mitigation strategies and an improved awareness of the highly transmissible nature of COVID-19 have over 95% of Americans on orders to stay at home. While therapeutic options to treat infected people continue to be investigated, it is apparent that an effective vaccine is needed to prevent people from contracting the deadly virus and enable the world to return to a sense of normalcy.

Prior estimates from Dr. Fauci, the director of the National Institute of Allergy and Infectious Diseases, for the development and approval of a potential vaccine were 12 to 18 months, which would be much faster than the typical time required for vaccine development. Data has shown that the rate at which SARS-CoV-2, the virus that causes COVID-19, mutates is not as rapid as the seasonal influenza virus. This is encouraging because if a vaccine becomes readily available within the next couple of years, it could have a prolonged effect by eliminating future cases. There are currently over 70 vaccines in various stages of development globally.

The Coalition for Epidemic Preparedness Innovations (CEPI) and the Biomedical Advanced Research and Development Authority (BARDA) have contributed hundreds of millions of dollars to develop and facilitate the costly process of finding a safe and effective vaccine. In addition, thirteen drug companies have agreed to collaborate and share their proprietary molecular compounds with a COVID-19 therapeutic accelerator launched by the Bill and Melinda Gates Foundation in an effort to expedite the development, manufacture and delivery of vaccines, diagnostics and treatments for COVID-19. Most notably, Novartis, Boehringer Ingelheim, Eli Lilly, Gilead, GlaxoSmithKline, Johnson & Johnson, Merck, and Pfizer are engaged in the race to develop the vital vaccine. GSK and Sanofi have joined forces in an unprecedented collaborative effort with the hopes that combining their resources and technology will have a synergistic effect.

Among the vaccine technologies under consideration are whole virus vaccines, recombinant protein subunit vaccines, and nucleic acid vaccines. Any drug or vaccine must go through three phases of clinical trials before FDA approval. There are two vaccines currently in Phase 1 of clinical trials in the United States, with many more being evaluated around the world. The purpose of Phase 1 trials is to determine the safety profile in healthy adults.

Moderna Therapeutics rapidly developed an early prospect for clinical trials on March 16^th, just 42 days after the genetic sequence for SARS-CoV-2 was released. Their candidate, known as mRNA-1273 is a novel lipid nanoparticle (LNP)-encapsulated mRNA-based vaccine that encodes for a stabilized spike (S) protein of SARS-CoV-2. In their Seattle based trial, forty-five healthy adults will be enrolled into one of three cohorts and will receive two intramuscular injections four weeks apart to assess the safety and reactogenicity of mRNA-1273, with subsequent evaluation at regular intervals over the course of 12 months. It is important to note that the biotechnology being utilized has been in existence for nearly 30 years, yet has never produced a viable, FDA-approved vaccine for any human disease. This highlights the fact that laboratory and animal studies cannot be extrapolated to determine appropriate use in humans.

Inovio Pharmaceuticals announced on April 6^th that the FDA accepted its application for INO-4800, its DNA vaccine candidate. DNA medicines are made of optimized DNA plasmids which are synthesized or reorganized by computer sequencing technology with the hopes of targeting a specific immune response. Preclinical data has shown positive immune response results across numerous animal models. The Phase 1 study of INO-4800 will enroll up to 40 healthy adults in Philadelphia and Kansas City where they will also receive two doses four weeks apart. Initial immune responses and safety data are expected to be available by late summer. Inovio plans to have a million doses of the vaccine manufactured by the end of the year for additional trials and emergency use, pending regulatory approval and funding.

Novavax announced on April 8^th that it has identified an “ideal” COVID-19 vaccine candidate and is set to begin their first clinical human trial in May. The candidate, known as NVX-CoV2373, has demonstrated an ability to produce immune responses and high levels of antibodies against COVID-19 in animal studies. NVX-CoV2373 uses antigens derived from the coronavirus spike protein to stimulate an immune response to provide protection against COVID-19. Novavax is working with another firm, Emergent BioSolutions, to expedite the process and they expect to have preliminary human data by July.

While vaccines undergo the beginning stages of development, treatment options continue to evolve with data from around the world. Researchers in the New England Journal of Medicine concluded that treatment with Remdesivir in a clinical trial of 53 people resulted in clinical improvement in 68% of patients. Rates of mortality, hospital discharges, and the ability to discontinue ventilator use were the factors considered in determining clinical improvement. No new safety concerns were observed, which is encouraging for an uninhibited approval process.

Hydroxychloroquine continues to be a top therapeutic candidate for the treatment of COVID-19 with clinical trials underway in nations worldwide. However, a trial studying use of high-dose and low-dose chloroquine in hospitalized patients in Brazil resulted in premature termination of the high-dose arm due to safety concerns after only 81 patients were treated. One of the most concerning adverse effects of chloroquine is QT prolongation and arrythmia, which is an irregular heart rate and may be fatal.  Azithromycin, an antibiotic often used in conjunction with hydroxychloroquine to treat COVID-19, is also known to produce QT prolongation in patients with certain cardiovascular disorders. For that reason, the American College of Cardiology, American Heart Association, and Heart Rhythm Society issued a joint statement outlining critical cardiovascular considerations for use of hydroxychloroquine and azithromycin for treatment of COVID-19.

Further studies and anecdotal reports of hydroxychloroquine treatment of COVID continue to be presented in the news. Reports include individuals such as a lawmaker, a New Jersey healthcare provider, and a former NFL player who believe that hydroxychloroquine helped them defeat the virus. Overall, these reports have been both positive and negative. A small study in France in eleven  consecutive patients failed to show an improvement of symptoms  and reduction in viral load after being treated with hydroxychloroquine (600 mg per day for 10 days) and azithromycin (500 mg day 1 and 250 mg days 2 to 5) and discusses a patient who experienced QT interval prolongation before treatment was discontinued. Another newly publicized study in Shanghai in 150 patients reported hydroxychloroquine failed to clear the virus better than standard care but patients receiving it did show improvement in clinical symptoms and a reduction of an important inflammatory marker in the blood. Side effects observed in this study were mostly mild and reported in half of the patients that received treatment. This prompted the study investigators to suggest that hydroxychloroquine’s potential effects against COVID-19 may be its anti-inflammatory mechanisms.

 A large scale study, titled “the Outcomes Related to COVID-19 treated with Hydroxychloroquine among In-patients with symptomatic Disease study” (ORCHID Study), in Tennessee has begun to evaluate the effects of the drug in a blinded, placebo-controlled randomized clinical trial of over 500 adults. The study is enrolling patients currently hospitalized with COVID-19 or in an emergency department with anticipated hospitalization. The National Institutes of Health (NIH) is overseeing this study, as well as one to evaluate Remdesivir in a similar manner. This is a significant development because prior studies were not conducted in a blinded, placebo-controlled randomized nature. These factors are indicative of a more valid scientific approach and are more likely to have an impact on FDA approval than small anecdotal type reports that were previously reported.

Convalescent plasma and hyperimmune globulin from individuals who have fought off the virus and have developed antibodies remain a viable treatment option. The blood obtained from these people may be administered to critically ill patients diagnosed with COVID-19. The FDA is leading a collaborative effort with partners from the pharmaceutical industry, academic institutions, and government partners to implement a protocol that would involve the MAYO clinic and the American Red Cross to collect and distribute plasma to patients around the country.

As the number of confirmed cases and deaths attributable to COVID-19 continue to mount, researchers continue to work diligently to evaluate which treatment options prove to be the most safe and effective. Vaccines remain the only way to eradicate such a disease and from having catastrophic effects in the future.

https://www.nationalgeographic.com/science/2020/04/why-coronavirus-vaccine-could-take-way-longer-than-a-year/

https://www.nejm.org/doi/full/10.1056/NEJMp2005630

https://clinicaltrials.gov/ct2/results?cond=COVID-19&term=vaccine&cntry=&state=&city=&dist=&Search=Search

https://bgr.com/2020/04/07/coronavirus-vaccine-update-who-wants-cures-to-be-widely-available/

https://nypost.com/2020/04/08/novavax-to-start-trial-for-ideal-coronavirus-vaccine-candidate/  

     

https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-blood-purification-device-treat-covid-19

https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-coordinates-national-effort-develop-blood-related-therapies-covid-19

https://www.beckershospitalreview.com/pharmacy/gilead-boosts-remdesivir-production-now-has-1-5m-doses.html

https://www.beckershospitalreview.com/pharmacy/13-drugmakers-form-consortium-to-find-covid-19-treatments.html

https://www.who.int/blueprint/priority-diseases/key-action/novel-coronavirus-landscape-ncov.pdf?ua=1

   

https://endpts.com/a-quick-slice-of-the-data-from-a-small-remdesivir-study-suggests-it-may-be-working-against-covid-19-but-all-the-big-questions-remain-to-be-answered/

https://www.the-scientist.com/news-opinion/covid-19-vaccine-frontrunners-67382

https://www.nih.gov/news-events/news-releases/nih-clinical-trial-hydroxychloroquine-potential-therapy-covid-19-begins

https://cepi.net/covid-19/

https://www.nytimes.com/2020/04/12/health/chloroquine-coronavirus-trump.html?auth=login-email&login=email

https://www.acc.org/latest-in-cardiology/articles/2020/04/10/15/06/acc-joins-aha-hrs-in-statement-on-exploratory-covid-19-treatment-drug-interactions-on-qtc

COVID-19 Treatment Options Update

The United States has surpassed China and Italy with the highest number of novel coronavirus (COVID-19) cases. As of March 30th, the US has an estimated 149,000 confirmed cases and 2,600 deaths spanning all 50 states and the District of Columbia. The rapid surge in positive cases is a testament to how contagious the virus is and the nationwide expansion of coronavirus testing.

Medical experts, including Dr. Anthony Fauci, Director of National Institute of Allergy and Infectious Disease, anticipate the virus could become a seasonal occurrence and the most effective way to prevent future pandemics would be a vaccine, like the seasonal flu shot.  However, coronavirus vaccines will require at least 12 to 18 months of clinical study before they are approved for use.

Meanwhile, clinical trials are underway worldwide to evaluate various treatments for coronavirus infected patients to identify those that are safe and effective.  Drugs under consideration include some that are available now because they are FDA approved to treat other diseases. Therefore, the possibility of repurposing these drugs to treat COVID-19 has been a primary focus for researchers.

Avigan (favipiravir) has demonstrated promise in shortening the duration of fever and cough in patients infected with COVID-19; also known as SARS-CoV-2. More importantly, as hospital admissions increase in the US, favipiravir has been shown to reduce the need for a ventilator in a clinical trial of 200 patients in the Chinese cities of Wuhan and Shenzhen. The shortage of ventilators, required to keep people alive and breathing in severe respiratory illnesses, is a major concern in the United States.

Perhaps the most extensively discussed COVID-19 treatment candidate is hydroxychloroquine, which was approved by the FDA today as an emergency treatment for COVID-19  along with other FDA approved conditions for this drug, i.e.  lupus, rheumatoid arthritis, and malaria. By now most people have heard about the French study of hydroxychloroquine in combination with azithromycin, an antibiotic commonly known as “Z-PAK”. The results of this study are promising; however, this positive news has led to unintended consequences. Pharmacists are seeing a massive increase in hydroxychloroquine prescriptions as physicians are prescribing it off-label for themselves and family members.

In efforts to contain this potential shortage, pharmacy benefit managers such as Express Scripts and CVS Health have implemented quantity limits and fill restrictions while state pharmacy boards have issued emergency restrictions on how the drugs can be dispensed. Walgreens now has a 14-day limit for new prescriptions and a 30-day supply limit for refills of hydroxychloroquine. Furthermore, medical authorities issued a warning about self-treatment after a tragic case of poisoning where an Arizona couple in their sixties were hospitalized after ingesting a form of chloroquine sold to clean fish tanks.

Remdesivir, a drug administered only intravenously, as opposed to oral drugs chloroquine and Avigan, remains a top candidate to become one of the first antiviral drugs to gain FDA approval in the United States. Remdesivir, which was originally being developed by Gilead to treat Ebola, incorporates itself into viral RNA and prevents the virus from replicating. It has shown in laboratory studies to be more effective against coronavirus than Avigan and chloroquine. With more clinical data showing safety and efficacy, it is feasible to see it gain FDA approval. Analysts from Seeking Alpha previously reported intravenous remdesivir would only be used for severe cases of COVID-19 infection. However, after positive reports of the effectiveness of Avigan, a related antiviral drug, they now also view remdesivir as a treatment for more moderate cases. Unfortunately, the most recent development with remdesivir is that its manufacturer, Gilead Sciences, is so backed up with compassionate use requests that it is now limiting its availability to clinical trial use.

Recent weeks brought two noteworthy updates about the HIV drug Kaletra (lopinavir/ritonavir) which has been studied around the world for COVID-10 treatment. AbbVie, the manufacturer of Kaletra altruistically suspended their global patent rights to help the global community with the supply of this drug. Unfortunately, the other noteworthy update was one of disappointment. In an article in the New England Journal of Medicine, researchers reported that Kaletra failed to show a benefit in reducing mortality rates and time to clinical improvement in a clinical trial of 199 people in China. To put this result in context, it is important to note that patients were very sick and had been symptomatic for two weeks before they started the treatment. However, the authors express their opinion that Kaletra was not particularly potent against COVID-19. Kaletra has been noted to be effective in other worldwide reports and continues to be studied for treatment of COVID-19.

Specialty drugs, Kevzara and Actemra, continue to be evaluated in the role they may play in dealing with the repercussions of lung inflammation caused by the coronavirus. If fewer patients progress from needing supplemental oxygen therapy to being intubated with a ventilator, scarce resources may be better used. Researchers are postulating that the aggressive immune response to COVID-19 that leads to lung inflammation and pneumonia is caused by what is known as a cytokine storm. Another drug that has promise in modulating cytokine storm and severe pulmonary complications of COVID-19 infection is leronlimab. Two critically ill patients in New York City were taken off ventilators and out of intensive care after they received leronlimab, an experimental drug being developed for HIV and breast cancer.

Serology testing, also known as antibody testing, allows researchers to evaluate how many people have been previously exposed to the virus and able to fight it off without being symptomatic. When a person is exposed to a disease-causing agent like SARS-CoV-2, their immune system produces antibodies to fight off infection. Antibody tests require only a small blood sample, are relatively inexpensive, and can produce results in about 15 minutes. It is possible antibody testing can be used to determine who can go back to work and who needs to stay home for a 14-day quarantine before returning to work.

New York, which has the highest number of confirmed cases and casualties in the country, is conducting a trial to test how effective convalescent plasma from people who have recovered from COVID-19 can be as a treatment. This method has previously been proven to be effective during the Spanish Flu epidemic of 1918, the SARS outbreak of 2003 and the Ebola epidemic of 2013. The infusion of convalescent plasma introduces antibodies that can illicit an effective immune response and shorten the duration and severity of infection.

As the effects of COVID-19 continue to create more devastation globally, the race to find a treatment and vaccine are of the utmost importance. Ongoing clinical trials and increased testing have helped to more accurately identify the magnitude of the virus’ traumatic effects and possibly identify safe and effective ways to treat those who are infected. Until then, precautionary measures remain the best way to avoid contracting the virus.

With a larger number of infected patients worldwide comes a greater set of data which scientists are able to leverage to gain a better understanding of how the virus is spread, the progression of symptoms, and most importantly which medications may be effective to reduce the severity of symptoms and shorten the time for an infected person to recover and test negative for the virus.

https://abcnews.go.com/Health/blood-tests-battle-covid-19-us/story?id=69761676

https://www.drugtargetreview.com/news/58608/remdesivir-most-promising-covid-19-drug-say-researchers/

https://www.fiercepharma.com/pharma-asia/top-covid-19-aspirants-chloroquine-abbvie-s-kaletra-and-a-flu-drug-disappoint-clinical

https://www.ibtimes.com/coronavirus-cure-new-york-treat-covid-19-blood-recovered-patients-2945195

https://medcitynews.com/2020/03/abbvies-hiv-drug-fails-covid-19-trial-in-china-but-a-fujifilm-flu-drug-may-have-efficacy/

https://www.nejm.org/doi/full/10.1056/NEJMoa2001282

https://nypost.com/2020/03/28/coronavirus-patients-taken-off-ventilators-after-getting-experimental-hiv-drug/?utm_campaign=iosapp&utm_source=mail_app

https://www.statnews.com/2020/03/27/serological-tests-reveal-immune-coronavirus/

https://seekingalpha.com/article/4334200-gileads-remdesivir-can-be-game-changer?li_source=LI&li_medium=liftigniter-widget

https://www.pharmacist.com/article/pharmacies-set-policies-stop-us-hoarding-potential-coronavirus-treatments

COVID-19 (CORONAVIRUS) TREATMENTS UNDER CONSIDERATION

At PBIRx, our highly experienced and educated Clinical Staff, including licensed registered pharmacists and PharmDs, have done careful research to share the following treatments that are being considered for use in the United States and/or being evaluated globally in clinical trials. It is important to note that as data continues to be collected, new treatment options will emerge.

COVID-19 (coronavirus) is a new global virus with currently no FDA approval of medications to treat infected patients or vaccines to prevent its rapid spread. However, since the virus began to infect and kill people in China in December 2019, medical professionals, including pharmaceutical manufacturers around the world, have been working to create a vaccine, while also evaluating many different drugs and combinations of drugs to treat and prevent COVID-19.  

It is important to note that all drugs have possible adverse effects and the research focuses on the possible risk of side effects versus potential efficacy in human patients. Agents being used at this time are being administered in an experimental setting under controlled conditions. No one is administered a drug for COVID-19 without a doctor’s authorization. Data on drug effectiveness and safety are collected by enrolling infected patients into clinical trials or through compassionate use as they are treated. Some of the drugs being used for COVID treatment are approved for other uses in the United States while others have only been used in other countries until now.

Treatment options often depend on many factors including age of patient, comorbidities, side effect risks, severity of coronavirus symptoms, patient specific allergies, and availability/accessibility, etc.

The first drug approved in China, or anywhere, to treat COVID-19 is Favilavir, known generically as favipiravir or under the brand name Avigan in Japan.  Avigan is an anti-viral drug that is active against RNA viruses and marketed in Japan for treatment of influenza.

According to China National Center for Biotechnology, Favilavir demonstrated an encouraging profile with mild adverse reactions in seventy (70) COVID-19 patients in a clinical trial in Shenzhen and Guangdong Provinces. The National Medical Products Administration of China has therefore approved the use of Favilavir, based on such clinical trials. Researchers noted that the drug has reportedly shown efficacy in hindering the spread and treating the disease with minimal side effects.

Favipiravir has also shown effectiveness in other reports of its treatment of COVID-19 in China. Chinese medical authorities reported positive responses in favipiravir clinical trials conducted in Wuhan and Shenzhen composed of 340 people. About 91% of infected patients treated with favipiravir showed improved lung function compared to 62% who did not receive any treatment and did not show improvement.   More significantly, those treated with favipiravir had a median of four (4) days to test negative, compared to eleven (11) days among those that did not receive treatment.  Some health officials noted that the results have not been as promising in people with a higher viral load and more severe symptoms. Favipiravir is also being developed in Japan for West Nile virus, yellow fever, and rabies.

Other drugs showing efficacy, which also do not have FDA approval in the US for COVID -19 treatment are the anti-malaria drugs hydroxychloroquine and chloroquine as well as Gilead’s experimental broad-spectrum antiviral drug remdesivir.

Hydroxychloroquine/chloroquine (brand name Plaquenil/Aralen, Resochin) are currently used in the United States and around the world to treat a variety of conditions that include malaria, lupus, and rheumatoid arthritis. Now they are being evaluated to determine if their use in COVID-19 infected patients leads to improved virological clearance and reduced mortality. President Trump announced on March 19^th that the FDA has approved testing of hydroxychloroquine and chloroquine for the treatment of COVID-19 through clinical trials and “compassionate use”. Below are links to publications describing 100 patients effectively treated with chloroquine in Wuhan, ten (10) hospitals throughout China effectively treating patients with hydroxychloroquine, and twenty four (24) patients in France effectively treated with chloroquine. The results in France are not officially published yet. 

The most recently talked about and seemingly most positive of all is a new study published in the International Journal of Antimicrobial Agents. The study was conducted after reports from the treatment of Chinese patients indicated that a combination of hydroxychloroquine with a popular antibiotic shortened the duration of COVID-19infection. The new study found early evidence that the combination of hydroxychloroquine and the antibiotic azithromycin (Zithromax, Z-pack) could be especially effective in treating the virus and reducing its duration in patients. The researchers performed this study in thirty (30) confirmed COVID-19 patients comparing hydroxychloroquine on its own or in combination with azithromycin to control patients (received neither treatment). Hydroxychloroquine was effective on its own and even more effective, by a significant margin, when combined with azithromycin.  

Hydroxychloroquine eliminated the COVID virus in over fifty (50) percent of patients in 6 days while the combination eliminated the virus all patients in five (5) days.  At enrollment, six (6) patients in the study presented with no symptoms (n=6), twenty two (22) patients presented with  upper respiratory tract symptoms (sneezing, headaches and sore throats, n=22), and eight (8) patients presented with lower respiratory tract symptoms (mostly coughing, n=8).

Remdesivir a broad-spectrum nucleoside inhibitor antiviral, also known as GS-5734, has received a lot of attention in the media. Remdesivir is under investigation by Gilead Sciences for treatment of Ebola virus (a filovirus) and has shown activity against other respiratory RNA viruses like SARS-CoV and MERS-CoV. The World Health Organization (WHO) has noted Remdesivir efficacy in treating the coronavirus in China. There are now several studies ongoing to establish its safety, effectiveness and dosing against COVID-19.  Four (4) of these studies are located within the United States. Of note, currently there are concerns with its safety. GI issues and elevated liver enzymes are most notable, although this is not uncommon with other anti-viral medications.

Kaletra (lopinavir and ritonavir), a drug used to treat HIV in the United States, is being evaluated beyond its current FDA indication, for use in COVID-19. There have been reports in both China and the US of its effectiveness in treating some COVID-19 patients. It was effective in combination with chloroquine in an HCP in New Jersey who said he “would be dead and gone” if not for this treatment. Kaletra, an antiretroviral agent has formerly been shown to be effective against severe acute respiratory syndrome (SARS) in-vitro. In clinical trials, the medication is being studied alone and in combination with other anti-viral drug ribavirin and with interferon.

Below are links to guidelines from China for COVID-19 treatments, including dosing used for lopinavir/ritonavir and other antivirals such as ribavirin.

Additionally, corticosteroids are being investigated in multiple trials for the novel virus. Steroids have been and continue to be used in the treatment of other severe coronavirus infections including SARS and MERS to manage symptoms. Several alarming concerns have arisen from those uses and interim guidance from the WHO recommends against using corticosteroids in patients with COVID-19 unless they have another indication.

A potential vaccine made by Moderna in collaboration with the National Institute of Allergy and Infectious Diseases is currently being evaluated and tested in the Seattle area. Their aim is to illicit the immune system to develop antibodies against a “spike protein” found on the virus.

Johnson & Johnson, Eli Lilly and Pfizer are also actively working to develop a vaccine.

The University of Minnesota is evaluating the hypertension drug losartan to see how effective it can be to reduce the risk of organ failure for hospitalized COVID-19 patients, and if it can reduce the need for hospitalization.

Specialty drugs like Kevzara and Actemra are also being tried in new ways to treat the lung inflammation caused by COVID-19.

The WHO identifies baloxavir (brand name Xofluza), a newer medication approved for influenza in the US, also as a possible COVID treatment candidate; however, there have been supply issues since the beginning of the flu season. It is important to note that the WHO is the only institution identifying Xofluza as a potential therapeutic candidate at this time. More well known in the United States is Tamiflu (oseltamivir) which has been recommended by WHO for influenza pandemics. Tamiflu is part of a clinical trial being held in Thailand that will combine it with protease inhibitors, favipiravir, and chloroquine for treatment of COVID-19.

Lastly, many reports advising against the use of the anti-inflammatory drug ibuprofen (brand name Motrin/Advil) have come out since Olivier Veran, the French health minister, tweeted last weekend about some patients in France experiencing serious side effects. However, the European Medicines Agency issued a statement on March 18^th that there is “currently no scientific evidence establishing a link between ibuprofen and worsening of COVID-19.” The World Health Organization tweeted: “Based on currently available information, WHO does not recommend against the use of ibuprofen. We are also consulting with physicians treating COVID-19 patients and are not aware of reports of any negative effects of ibuprofen, beyond the usual known side effects that limit its use in certain populations.”

In summary, at this time it remains to be determined how to most effectively treat (and hopefully soon prevent) COVID-19. The global medical community continues to work diligently to minimize the effects of COVID-19 and as new data becomes available, treatment options will inevitably continue to be updated in this rapidly evolving fluid pandemic. It is vital to keep in mind to follow the guidelines of official legitimate sources like your medical professional, the CDC and the WHO to minimize the risk and spread of this virus.

https://www.clinicaltrialsarena.com/analysis/coronavirus-mers-cov-drugs/

https://www.connexionfrance.com/French-news/French-researcher-in-Marseille-posts-successful-Covid-19-coronavirus-drug-trial-results

https://www.forbes.com/sites/alexknapp/2020/03/13/coronavirus-drug-update-the-latest-info-on-pharmaceutical-treatments-and-vaccines/#53ab4fac21db

https://www.jbc.org/content/early/2020/02/24/jbc.AC120.013056.full.pdf

https://www.jstage.jst.go.jp/article/bst/14/1/14_2020.01047/_pdf/-char/en

https://www.jstage.jst.go.jp/article/ddt/14/1/14_2020.01012/_pdf/-char/en

https://news.worldusheadlines.com/2020/03/19/two-generic-drugs-being/

https://www.npr.org/sections/health-shots/2020/03/18/818026613/advice-from-france-to-avoid-ibuprofen-for-covid-19-leaves-experts-baffled

https://nypost.com/2020/03/18/japanese-flu-drug-clearly-effective-in-treating-coronavirus-officials-say/?utm_campaign=iosapp&utm_source=mail_app

https://www.pharmacytimes.com/news/potential-pipeline-medications-for-the-coronavirus

https://www.theguardian.com/world/2020/mar/18/japanese-flu-drug-clearly-effective-in-treating-coronavirus-says-china

https://www.who.int/blueprint/priority-diseases/key-action/novel-coronavirus/en/

https://techcrunch.com/2020/03/19/french-study-finds-anti-malarial-and-antibiotic-combo-could-reduce-covid-19-duration/

https://nypost.com/2020/03/12/hiv-drugs-are-being-used-as-part-of-coronavirus-treatment/

Chaos at Chain Pharmacies

It’s every pharmacist’s worst nightmare…making a serious prescription error while they are rushing to fill prescriptions for waiting customers. Yet this nightmare becomes a reality all too often, even more so now than in the past, as the computer age has everyone accustomed to instant customer service. Many pharmacists believe that even one Rx error is too many.

Last Saturday the New York Times published a front page story titled:

“How Chaos at Chain Pharmacies Is Putting Patients at Risk”

In letters to state regulatory boards and in interviews with The New York Times, many pharmacists working at chain pharmacies like CVS, Rite Aid and Walgreens described understaffed and chaotic workplaces where they said it had become difficult to perform their jobs safely, putting the public at risk of medication errors. They struggle to do all of the following things, while racing to meet corporate performance metrics that they characterized as unreasonable and unsafe in an industry squeezed to do more with less:

• Fill prescriptions
• Administer vaccinations
• Tend the drive-through
• Answer phones
• Work the cash register
• Counsel patients
• Call prescribers' offices
• Call insurance companies
• Handle inventory

Michael Jackson, chief executive of the Florida Pharmacy Association, said the number of complaints from members related to staffing cuts and worries about patient safety had become “overwhelming” in the past year. Regulating the chains can be difficult; Florida’s nine-member state pharmacy board includes a lawyer for CVS and a director of pharmacy affairs at Walgreens. Pharmacists are often afraid to speak up, fearing retaliation. The chains deny that their pharmacists are under extreme pressure, yet their bonuses are often tied to the number of prescriptions they fill and call lists completed.

CVS accounts for one-fourth of the United States’ total prescription revenue and dispenses more than 1 billion prescriptions per year; Walgreens captures about one-fifth. The chains declined to provide data about the numbers of mistakes made, and much of the information never becomes public because companies often settle with their victims out of court, requiring a confidentiality agreement. A CVS form that staff members use to report errors asks whether the patient is a “media threat”. The last study made public was in 2006; it concluded that pharmacy mistakes harm 1.5 million Americans annually.

“A fatigued and distracted pharmacist in a fast-paced, chaotic environment is much more likely to make an error. The harm from such an error ranges from being a slight inconvenience to being fatal.”

--An anonymous Texas pharmacist

https://www.nytimes.com/2020/01/31/health/pharmacists-medication-errors.html

What can your members do to prevent errors?

Take an active role in your health

• Compare prescription information from your prescriber to the medication you pick up at the pharmacy/ prescriptions delivered to you (if using mail order).
• Familiarize yourself with drug names, dose, dosage forms, and directions to help identify a possible error before it impacts your health.
• Access pharmacy apps and digital tools where you can review your pertinent prescription history.

Ask your pharmacist

• One of the most important responsibilities your pharmacist has is patient consultations
• Utilize them as an expert source of information regarding your prescriptions. This allows your pharmacist to take another look to review your prescription to ensure there are no errors.

Utilize free resources

• Carefully read and examine your prescription label; it contains information about the appearance of the tablets/capsules/liquid etc. 
• Cross-reference that to what appears inside the vial.
• Do not assume it is a change in manufacturer or supplier. Free websites like www.drugs.com  and www.WebMD.com  can help identify drugs.