Virus World

The U.S. Food and Drug Administration has approved a kit that will allow women to collect their own vaginal sample for HPV screening, a move that could increase early detection in those at risk for cervical cancer. Women will be able to swab themselves in privacy at a doctor's office, clinic or pharmacy, and the sample will then be sent off for analysis. More than half of U.S. women diagnosed with cervical cancer have never been screened or screened only infrequently for the virus, the kit's maker Roche said in a news release announcing the approval on May 15 2024. "With vaccinations, innovative diagnostic tools and screening programs, achieving the WHO's goal of eliminating cervical cancer by 2030 is within reach," Roche Diagnostics CEO Matt Sause said. "Our HPV self-collection solution helps support this goal by reducing barriers and providing access to HPV screening by allowing people to privately collect their own sample for HPV testing." Each year, about 11,500 U.S. women are diagnosed with cervical cancer and about 4,000 women die from it, according to the U.S. Centers for Disease Control and Prevention. HPV is the known cause of more than 95% of cervical cancers, Roche added. "Almost all cervical cancers are caused by persistent infection with certain types of HPV," Dr. Karen Knudsen, CEO of the American Cancer Society (ACS), said in a statement. "Self-collection can expand access to screening and reduces barriers, which will give more people the opportunity to detect, treat and ultimately survive cancer."

Most primary care doctors don't test for HPV. Instead, women are most often screened by gynecologists during a pelvic exam, a procedure to which some don't have access and others find too intrusive and embarrassing. "Roche's self-collection solution can help reduce these barriers by offering an alternative to clinician collection procedures, while also providing accurate and reliable results," Roche said. The HPV test itself is already covered by private insurance, Medicare and Medicaid, Roche told the Washington Post. "This literally just opens up another option for a different demographic of people that might not feel comfortable, that might not have access [and] may not have time" to get tested otherwise, Irene Aninye, chief science officer for the Society for Women's Health Research, told the Post. The ACS recommends that cervical cancer screening begin at age 25, and that women ages 25 to 65 have an HPV test every five years.

Studies done for the past two decades have found that self-collection for HPV testing is feasible and acceptable, and that women can collect samples as well as their physicians, the ACS said. "Self-collection was not FDA-approved at the time our current guideline was released, but we now expect a minor update to the guideline to note that primary HPV testing via clinician-collected sample or self-collection is acceptable," said ACS Chief Scientific Officer Dr. William Dahut. "We anticipate self-collection will play an increasingly prominent role in cervical cancer screening once regulatory and clinical prerequisites are in place and as supporting evidence continues to accumulate," Dahut added. The approval could also open the door for at-home collection of samples. Teal Health received FDA breakthrough designation last week for an at-home cervical cancer screening device called the Teal Wand. Women would collect their own sample at home, then send it to a lab to be tested for HPV. The designation grants Teal Health priority status from regulators when clinical trials wrap up and the data is submitted to the FDA. "No more stirrups, no more speculum," the Teal Health website promises. "The Teal Wand replaces the need for an in-office pap smear using stirrups, a speculum and a hard plastic brush or broom. With self-collect, you are in control."

Roche's Press release (May 14, 2024):

https://www.roche.com/media/releases/med-cor-2024-05-15 

New late-stage trial data show Regeneron and Roche's antibody cocktail against COVID-19 cut hospitalisation or death by 70% versus a placebo in non-hospitalised patients, the Swiss drugmaker said on Tuesday. The shot, consisting of casirivimab and imdevimab antibodies developed by Regeneron with financial help from the U.S. government, also met all key secondary endpoints in the phase III trial with 4,567 participants, including reducing symptom duration to 10 days from 14, Roche said.  Roche, which is making the drug at plants in California and which is responsible for sales outside the United States, and Regeneron are expecting hundreds of millions in sales in 2021 from the drug, including $260 million alone to the U.S. government in the first quarter. 

“New infections continue to rise globally with over three million reported cases last week, so this investigational antibody cocktail may offer hope as a potential new therapy to high-risk patients - particularly in light of recent evidence showing that casirivimab and imdevimab together retain activity against key emerging variants,” Roche Chief Medical Officer Levi Garraway said.  Roche has said that it and Regeneron can produce more than 2 million doses annually. The cocktail, which data previously showed has been effective against variants, has emergency approval in the United States, and has been authorized in Europe for use in non-hospitalised patients. Former U.S. President Donald Trump got the treatment when he was infected with COVID-19.

Roche's Press Release (March 23, 2021):

https://www.roche.com/media/releases/med-cor-2021-03-23.htm

Roche is paying Atea Pharmaceuticals $350 million upfront for the ex-U.S. rights to COVID-19 antiviral AT-527. The oral direct-acting antiviral is set to enter a phase 3 trial in non-hospitalized patients early next year, giving Roche and Atea a shot at establishing it as the go-to early treatment for COVID-19. Atea put its COVID-19 program on the map in May when it raised $215 million in a round led by Bain Capital Life Sciences. Up to that point, Atea was perhaps best known for being set up by Jean-Pierre Sommadossi, co-founder of Sovaldi developer Pharmasset. 

Reflecting Sommadossi’s background, Atea initially studied its oral purine nucleotide prodrug AT-527 in hepatitis C, before the pandemic and in vitro evidence of efficacy in coronaviruses persuaded it to target SARS-CoV-2. A phase 2 trial of 190 hospitalized patients with moderate COVID-19 got started in May and is due to wrap up around the end of the year, according to ClinicalTrials.gov.  “AT-527 is expected to be ideally suited to combat COVID-19 as it inhibits viral replication by interfering with viral RNA polymerase, a key component in the replication machinery of RNA viruses,” Sommadossi said in a statement. The phase 2 results will provide a clearer picture of whether AT-527 is efficacious in COVID-19, but Roche has already seen enough to bet $350 million and commit to milestones and royalties. The outlay secures Roche ex-U.S. rights to AT-527. Atea will retain responsibility for distributing the drug in the U.S., although it has an option to ask for the support of Roche’s Genentech. 

While AT-527 is currently in development in hospitalized patients, Roche centered its discussion of the value of the drug on its potential role in non-hospitalized patients. As an oral small molecule, AT-527 has several potential advantages over anti-SARS-CoV-2 antibodies outside of hospital settings. AT-527 stands to be cheaper, easier to administer and manufactured at larger quantities.  Atea and Roche plan to start a phase 3 trial in non-hospitalized patients in the first quarter of 2021. By then, the U.S. and other countries may have begun vaccinating their populations against the novel coronavirus, thereby beginning the process of bringing the pandemic under control. However, with the rollout of immunization programs taking time and vaccines likely to only offer partial protection, Atea and Roche are betting there will remain a need for treatments for some time.   Roche foresees AT-527 being used to treat patients early, perhaps even in post-exposure prophylactic settings. Widespread access to an effective early treatment could stop some cases from progressing to severe COVID-19, thereby improving patient outcomes and reducing the burden on healthcare systems.  The deal opens up another front in Roche’s response to the pandemic. In August, Roche secured the ex-U.S. rights to Regeneron’s REGN-COV2, securing itself a leading spot in the race to bring COVID-19 antibody therapies to market. The deals position Roche to apply its development and manufacturing muscle to drugs with the potential to defang SARS-CoV-2.

The FDA has issued an emergency use authorization for tocilizumab to treat hospitalized patients receiving corticosteroids who require supplemental oxygen, mechanical ventilation or extracorporeal membrane oxygenation, according to a press release. The emergency use authorization for tocilizumab (Actemra, Genentech) — now the fourth monoclonal antibody authorized for COVID-19 — is is specifically for hospitalized adults and children aged 2 years and older; it is not intended for outpatients or as a treatment for COVID-19, the FDA noted.  “Today’s action demonstrates the FDA’s commitment to making new therapies available through every stage of the global COVID-19 pandemic,” Patrizia Cavazzoni, MD, director of the FDA’s Center for Drug Evaluation and Research, said in a press release. “Although vaccines have been successful in decreasing the number of patients with COVID-19 who require hospitalization, providing additional therapies for those who do become hospitalized is an important step in combating this pandemic.”

The FDA based its emergency use authorization on results from four randomized, controlled trials — RECOVERY, EMPACTA, COVACTA and REMDACTA — that evaluated the safety and efficacy of tocilizumab in more than 5,500 hospitalized patients with COVID-19. In particular, the RECOVERY and EMPACTA trials provided the “most important scientific evidence on the potential benefit of Actemra for its authorized use,” the FDA noted. In the RECOVERY trial, hospitalized patients with severe COVID-19 pneumonia (n=4,116) were randomized to receive either tocilizumab plus standard care (n=2,022) or standard care alone (n=2,094). The primary endpoint was death through 28 days of follow-up.

According to the FDA, the “results of the primary analysis were statistically significant” with the probability of death by day 28 estimated to be 30.7% for patients receiving tocilizumab and 34.9% for patients receiving standard care alone. Additionally, the median time to hospital discharge was 19 days in the tocilizumab group compared with more than 28 days in the standard care group. Supplemental data from the EMPACTA trial, in which hospitalized patients with COVID-19 pneumonia (n=389) were randomized to receive tocilizumab (n=249) or standard care (n=128), demonstrated a lower risk for progression to mechanical ventilation or death by day 28 in hospitalized patients who received tocilizumab (12% vs. 19.3%). “Even with the availability of vaccines and declines in deaths from COVID-19 in various parts of the world, we continue to see new hospitalizations from severe forms of the disease,” Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Genentech, said in a company press release. “We are pleased that Actemra is now authorized as an option that may help improve outcomes for adults and children hospitalized with COVID-19 in the United States.” The emergency use authorization requires that fact sheets be made available to health care providers and patients, parents and caregivers featuring information on the potential side effects, which include constipation, anxiety, diarrhea, insomnia, hypertension and nausea.

See also FDA information (June 24, 2021):

https://www.fda.gov/media/150345/download 

The U.S. Food and Drug Administration (FDA) expanded the approved indication for Xofluza (baloxavir marboxil) to include post-exposure prevention of influenza (flu) for patients 12 years of age and older after contact with a person who has the flu, according to press releases Xofluza, previously available only in tablet form, is also now available as granules for mixing in water. Xofluza was originally approved in 2018 for treating uncomplicated flu in patients 12 years of age and older who have been symptomatic for no more than 48 hours. “This expanded indication for Xofluza will provide an important option to help prevent influenza just in time for a flu season that is anticipated to be unlike any other because it will coincide with the coronavirus pandemic,” said Debra Birnkrant, MD, Director of the Division of Antiviral Products in the FDA’s Center for Drug Evaluation and Research. “Americans will have to be more vigilant than ever as these viruses spread concurrently.”

In addition, Roche, the developer of the product, said it is determining a path forward with the FDA for a potential indication for Xofluza as a treatment for acute uncomplicated influenza in otherwise healthy children from one to 12 years of age and for the prevention of influenza in the same age group who have been exposed to influenza. Xofluza is currently not approved for use in this population, Roche said. Xofluza’s safety and efficacy for post-flu exposure prevention is supported by one randomized, double-blind, controlled trial in which 607 subjects, 12 years of age and older who were exposed to a person with influenza in their household, received either a single dose of Xofluza or a single dose of a placebo. Of these 607 subjects, 303 received Xofluza and 304 received the placebo. The trial’s primary endpoint was the proportion of subjects who were infected with influenza virus and presented with fever and at least one respiratory symptom from day one to day 10. Of those who received Xofluza, 1 percent of subjects met these criteria, compared to 13 percent of subjects who received a placebo for the clinical trial.

FDA Press Release (Nov, 23, 2020):

https://www.fda.gov/news-events/press-announcements/fda-expands-approval-influenza-treatment-post-exposure-prevention

The popular prescription influenza antiviral will become more accessible in the United States thanks to Sanofi deal. In July 2019, manufacturer Sanofi said it had signed a deal with Roche Pharmaceuticals to obtain exclusive OTC rights for the antiviral agent Tamiflu (oseltamivir phosphate), a neuraminidase inhibitor indicated for the treatment and prophylaxis of the influenza virus. “The US market is the largest OTC market in the world, and a successful switch of Tamiflu to OTC would support our global cough and cold strategy by expanding into flu with a sustainable point of difference in the market,” Sanofi said in a statement. The company has not announced an exact date of availability of OTC Tamiflu. Under the agreement, in addition to leading the FDA negotiations, Sanofi will head the clinical program and fund all studies needed to support the OTC switch in the United States in consultation with leading experts in the field.1 Tamiflu is currently sold in the United States by Genentech, a member of the Roche Group, for prescription use. Roche will continue to market Tamiflu in the rest of the world. Sanofi will retain the rights to first negotiations for switch rights in other select markets.

The pending switch of Tamiflu from prescription to OTC status will augment accessibility of this effective antiviral, allowing patients to initiate therapy to prevent or treat the influenza virus early on. Pharmacists are in a pivotal position to increase awareness and educate patients about the influenza virus, including prevention and treatment options. Once Tamiflu becomes available as an OTC medication, pharmacists will likely encounter many questions from patients about this agent, and they should be prepared to counsel them about its proper use, dosing, and adverse effects. During counseling, pharmacists should seize every opportunity to encourage and remind patients, especially those in high-risk populations, to get the yearly influenza vaccine. They can also dispel common misconceptions and myths about the influenza vaccine. Finally, they can inform patients that the vaccine is the most effective way to prevent the influenza virus and has been shown to be beneficial in diminishing the risk of influenza virus illness, hospitalization, and even the risk of death due to influenza-related complications, such as pneumonia, especially among elderly and pediatric patients. 

Currently, OTC medications marketed for influenza are limited to and intended to provide only symptomatic relief from the common symptoms associated with the influenza virus, such as body or muscle aches, chills, fever, headache, nasal congestion, and sore throat. Examples of these medications include analgesics, antipyretics, cough medications, and decongestants. Additionally, OTC homeopathic medications for management of the influenza virus are available. Although most people recover from the influenza virus after a week or so, certain patient populations, such as geriatric and pediatric patients and those with certain medical conditions, are at greater risk for complications. The annual influenza vaccination rates in the United States are still considered suboptimal, and many people are not aware of the availability of prescription antivirals to prevent and treat the virus. The CDC has designated the 2018-2019 influenza season as the longest in a decade.2 A total of 130 pediatric deaths occurred during that influenza season, according to the most recent report from the CDC.3 The highest rate of hospitalization occurred among adults 65 years and older.3 In preliminary approximations for October 1, 2018, through May 4, 2019, the CDC reported that an estimated 42.9 million people had the flu during the 2018-2019 flu season, 647,000 people were hospitalized, and 61,200 deaths occurred.

On average, more than 31 million individuals annually in the United States are afflicted with the influenza virus during its peak season in the fall and winter months, according to a CDC report. The CDC also indicated that just 7 million individuals actually receive the appropriate antivirals to treat the influenza virus.4 The CDC has conducted limited qualitative research into clinician knowledge, attitudes, and practices related to these antiviral medications. The findings suggest that many possible factors are involved in the underprescribing of antivirals. These include an extensive range in perception about how well these medications work and minimal clinician awareness of the CDC’s antiviral recommendations.4 In addition, some clinicians may not prescribe antivirals after the 2-day window when benefit is optimal, and some may require a positive flu test before prescribing antivirals, even though the results of rapid influenza diagnostic tests, if ordered, may not be accurate.