Ritonavir

Paxlovid, effective in preventing severe COVID-19, didn't appear to help long-COVID patients in this single-center study. But further research may show benefits with different doses or for people with specific symptoms. In a clinical trial conducted by Stanford Medicine investigators and their colleagues, a 15-day course of Paxlovid -- an antiviral drug combination targeting SARS-CoV-2, the virus that causes COVID-19 -- proved safe as an extended-duration treatment but didn't lessen select symptoms of the syndrome known as long COVID: the persistence, or reappearance, of COVID-related symptoms three months or more after an initial COVID-19 infection. The findings are described in a paper to be published June 7 in JAMA Internal Medicine. Paxlovid is a highly effective antiviral agent licensed for treatment of acute COVID-19. It's approved by the Food and Drug Administration for the treatment of adults who are newly infected with SARS-CoV-2, have mild or moderate COVID symptoms, and are at high risk of complications because of age or various predisposing conditions. A five-day Paxlovid regimen has been shown to reduce recipients' likelihood of hospitalization and death by more than 85%. While the Stanford trial did not show that Paxlovid reduced long COVID symptoms, it did show that taking the drug for more than two weeks was safe. "We've demonstrated the overall safety of a 15-day course of Paxlovid -- that's three times as long as it's being taken for acute COVID," said Linda Geng, MD, PhD, clinical associate professor of primary care and population health, who was one of the trial's two co-principal investigators. Geng is the paper's lead author. Its senior author is the trial's other co-principal investigator, Upinder Singh, MD, professor and chief of infectious disease and geographic medicine and of microbiology and immunology. Desperate people "While there are now improved therapies and treatment practices for acute COVID, there's nothing FDA-approved for long COVID, people continue to suffer and the numbers keep piling up," Geng said. An estimated 10% to 20% of SARS-CoV-2-infected people -- tens of millions in the United States alone -- develop long COVID. That estimate is fuzzy, because the definition of long COVID is ambiguous. More than 200 separate symptoms have been ascribed to the syndrome. These symptoms are often shared by other conditions, making a definitive diagnosis hard to pin down. It may well be that long COVID is a collection of different diseases set in motion by acute COVID but with different underlying mechanisms and effects and accordingly distinct methods required to alleviate them. Indeed, numerous causes of long COVID have been posited. Among them are virus-induced changes in our resident gut bacteria; residual inflammatory overdrive; COVID-spurred autoimmunity; and the reawakening of other infectious viruses that have woven themselves into our genomes and remained dormant, only to emerge when our SARS-CoV-2-preoccupied or exhausted immune systems let their guard down. The randomized, controlled, double-blinded phase 2 trial, known as STOP-PASC, is the first such test of Paxlovid treatment for long COVID. (STOP stands for Selective Trial of Paxlovid. PASC is an acronym for Post-Acute Sequelae of COVID, medical scientists' formal name for long COVID.) The trial was designed to explore the so-called viral-reservoir hypothesis of long COVID: the possibility that while initial symptoms may have abated and measured viral counts gone to zero, the virus or viral debris persists in deep tissues, hiding out and perhaps replicating slowly there. "Some studies suggest that viral particles and molecular debris could be responsible for some long-COVID sufferers' ongoing symptoms," Singh said. "We figured if that's the case, maybe treating them with Paxlovid could relieve some of these symptoms." There are anecdotal reports of Paxlovid providing relief for long-COVID symptoms. "We've observed long-COVID patients who've improved after taking Paxlovid for new infections," said Geng, who co-directs Stanford's long-COVID clinic. The trial Between November 2022 and September 2023, Geng, Singh and their colleagues enrolled and followed 155 trial participants who'd tested positive for SARS-CoV-2. All but two had been vaccinated. Demographically, they broadly reflected the San Francisco Bay Area's ethnic distribution. Their median age was 43; about two-thirds were between 34 and 54 years old. On average, participants had been initially infected more than 16 months before enrolling in the trial. Yet, each participant reported moderate to severe cases of at least two out of six common "core" long-COVID symptoms: fatigue, brain fog, shortness of breath, body aches, and cardiovascular or gastrointestinal symptoms. Half of the study participants were randomized to a 15-day course of Paxlovid; the others received a placebo along with low dosages of one of the two separate drugs that, combined, constitute Paxlovid. Both of these drugs are antiviral agents, but only one of the two, nirmatrelvir, has been found effective against SARS-CoV-2. The other drug, ritonavir, has no direct efficacy against this virus, but it ties up some of the same liver-resident enzymes that break down nirmatrelvir, boosting nirmatrelvir's effective concentration in the body. Because ritonavir can cause an easily recognized side effect -- a metallic taste in the mouth -- the investigators added it to the placebo formulation so placebo recipients wouldn't be able to distinguish it from the active drug, and vice versa. Partway through the study, the data was submitted to an independent group for preliminary analysis. On determining that safety appeared to pose no problem but no benefit was yet evident, the researchers continued the trial but stopped recruiting new participants. At 10 weeks, the prespecified time point for the final comparison, there was no statistically significant difference between the two groups in the study's primary endpoint: a reduction in the severity of the six core symptoms. Nor was there any detectable divergence between the two groups in numerous secondary outcomes such as seated and standing blood pressure and heart rates, and performance on the one-minute "sit and stand" test (subjects are asked to sit in a chair, stand up and sit down again repeatedly as fast as they can for a minute). The 15-day drug regimen was, however, safe. There was one serious, possibly trial-related adverse event (hepatitis) among the placebo recipients, while the three cases of serious adverse events experienced by Paxlovid recipients (blood loss anemia, forearm fracture and melanoma) were judged to be unrelated to the drug treatment. "One reasonable implication of our results is that Paxlovid can be given safely for a longer period of time," Singh said, "for example, in instances where a newly infected patient is immunocompromised." The challenge of being first The apparent absence of a clinical response in the recent trial doesn't rule out the possibility that Paxlovid might be found to reduce long-COVID symptoms in some people, Singh said, remarking that too many questions remain unanswered: "Should we have tested patients with symptoms present after only seven or eight months instead of 16 or 17? Should we have treated them for a longer time? Were we even testing the right patients? Maybe only some symptoms will be responsive to antiviral treatment." If long COVID is not a single entity, the required treatment could differ among people exhibiting different clusters of symptoms. Even routine testing of participants for the initial or post-treatment presence of cryptic SARS-CoV-2 -- which by definition would be tucked away out of reach of the immune system and, perhaps, simple blood tests -- was a nonstarter, Singh said, because simple, noninvasive, cheap tests are nonexistent. Intriguingly, on average both the intervention- as well as placebo-arm participants' overall symptoms improved over the course of the study. That could be good news, indicating that long-COVID symptoms generally subside with time. On the other hand, there's the possibility of a placebo effect: The extra attention and concern from nurses, doctors and other health-provider types, as well as the hope of relief from the drug, may nudge placebo recipients to sense subjective improvement -- or even to experience objective improvement -- in their condition. Plus, the absence of validated objective biomarkers made it tough to tell if one person's reported improvement was bigger than another person's. Results from a number of chemical tests, immunological tests and wearables measurements taken throughout the trial may help the Stanford Medicine team find out whether some people benefited considerably more than others from Paxlovid and, if so, how they might be distinguished in advance of treatment or enrollment in a new trial. "We hope to report on our analyses of these measurements in four to six months," Singh said. The results may inform other clinical trials, now underway or in planning stages, of Paxlovid and other drugs' capacity to counter long-COVID symptoms. These trials are sponsored by the National Institutes of Health as well as by Pfizer, Inc., Paxlovid's developer, manufacturer and marketer. Researchers from Kaiser Permanente North California and Pfizer contributed to the work. The trial was funded by Pfizer.

Study paves the way toward a first-ever innovation program to include AI-optimization for FDA-guided Rx-to-OTC switch NEW YORK, NY / ACCESSWIRE / May 29, 2024 / Petros Pharmaceuticals, Inc. (NASDAQ:PTPI) ("Petros" or the "Company"), a company focused on expanding consumer access to medication through over-the-counter ("OTC") drug development programs, announces the successful completion of a Formative Human Factors study of its AI-integrated Web App, designed to facilitate OTC access of STENDRA® (avanafil) for consumers. This important development follows the Company's recent execution of an AI licensing agreement with a leading multi-billion dollar software provider announced earlier this year. The Web App (previously referred to as the "technology component") is an integral part of the Company's efforts to complete an Rx-to-OTC switch for STENDRA® (avanafil) under the guidance of the U.S. Food and Drug Administration. The study demonstrated a 90% or better error-free completion rate for nearly all 5,820 tasks assessed. The successful completion of the study paves the way for the Company to initiate the next stage of the evolving program, while continuing to optimize the AI component of the Web App. "The successful completion of the Human Factors Study and the positive outcomes we've seen to date continue to be encouraging signs of our progress in navigating the Rx-to-OTC switch for STENDRA® (avanafil). As we've previously indicated, we believe we have the potential to be first-in-class for the category with regards to OTC access," stated Fady Boctor, Petros' President and Chief Commercial Officer. "We continue to refine our program based on our regular interactions with the FDA, and the learnings from this study will allow us to continue to optimize the AI component of the Web App. Combined, we strongly believe in our approach and look forward to continuing development into the next indicated step for STENDRA® (avanafil) in a non-prescription setting." The Formative Human Factors study was conducted in a population of 30 consumers, including a cohort with limited literacy. The consumers were provided with five different use scenarios requiring correct demonstration of 194 different tasks using the Web App with no training or guidance. The study also included a proprietary AI interface that confirmed the identity of the consumer, a first-ever innovation for an Rx-to-OTC switch program. About Petros Pharmaceuticals Petros Pharmaceuticals, Inc. is committed to the goal of becoming a leading innovator in the emerging self-care market driving expanded access to key prescription pharmaceuticals as OTC treatment options. Currently, Petros is pursuing increased access for its flagship prescription ED therapy, STENDRA® (avanafil), via potential OTC designation. If ultimately approved by the FDA for OTC access, STENDRA® (avanafil) may be the first in its class to achieve this marketing status, also establishing company know how as a proven platform for other prospective prescription therapeutics. About the OTC Pathway The process of switching a prescription medication to OTC first involves the design of a Drug Facts Label ("DFL") that is well understood by potential consumers. Then, data must show that consumers can make an appropriate informed decision to use or not to use the product based only upon the information on the DFL and their personal medical history. Then consumers must demonstrate that they can properly use the product based upon the information on the DFL. To accomplish this, the FDA ordinarily requires a consumer tested OTC DFL. Such testing includes conduct of iterative Label Comprehension Studies (LCS) in the general population, Self-Selection Studies (SSS) in a population interested in using the product and in specific populations who may be harmed if they use the product, and usually one Actual Use Trial (AUT) demonstrating safe and appropriate use by consumers in a simulated OTC setting. The regulations that FDA is currently finalizing introduced Additional Conditions for Nonprescription Use (ACNU) criteria that enable correct self-selection by consumers and may expand OTC access to medications that formerly could only be available by prescription. An ACNU may be an innovative computerized tool, or the additional conditions may use other approaches that support the switch process. Important Safety Information about STENDRA® (avanafil) STENDRA® (avanafil), originally launched by Auxilium Pharmaceuticals prior to its sale to Endo Pharmaceuticals, is an oral phosphodiesterase 5 (PDE5) inhibitor for the treatment of erectile dysfunction. STENDRA® (avanafil) is not for use in women or children. It is not known if STENDRA® (avanafil) is safe and effective in women or children under 18 years of age. A 100-mg and 200-mg tablet can be taken as early as ~15 minutes before sexual activity. STENDRA® (avanafil) only works with sexual stimulation and should not be taken more than once a day. STENDRA can be taken with or without food; do not drink too much alcohol when taking STENDRA® (avanafil) (for example, more than three glasses of wine or three shots of whiskey) as it can increase chances of side effects. Of people enrolled in clinical trials, 1.4%, 2.0%, and 2.0%, respectively, stopped taking STENDRA® (avanafil) (50 mg, 100 mg, or 200 mg) due to side effects compared to 1.7% taking a placebo. STENDRA® (avanafil) was designed and developed expressly for erectile dysfunction. STENDRA is contraindicated for any form of organic nitrates, in patients with known hypersensitivity to any component of the tablet, and in patients who are using a guanylate cyclase stimulator. Patients should not use STENDRA if sexual activity is inadvisable due to cardiovascular status or any other reason. Before taking STENDRA, tell your doctor if you have had any kind of heart issues including heart attack, heart failure, angina and irregular heartbeat or have elevated or low blood pressure. Use of STENDRA with alpha-blockers, other antihypertensives, or substantial amounts of alcohol (greater than three units) may lead to hypotension. Patients should seek emergency treatment if an erection lasts greater than 4 hours. Patients should stop STENDRA and seek medical care if a sudden loss of vision occurs in one or both eyes, which could be a sign of Non-Arteritic Ischemic Optic Neuropathy ("NAION"). Doctors should discuss with patients the increased risk of NAION in patients with a history of NAION. Patients should stop taking STENDRA and seek prompt medical attention in the event of sudden decrease or loss of hearing. STENDRA can potentiate the hypotensive effect of nitrates, alpha blockers, antihypertensives, and alcohol. CYP3A4 inhibitors (e.g., ketoconazole, ritonavir, erythromycin) increase STENDRA exposure. For patients taking concomitant strong CYP3A4 inhibitors (including ketoconazole, ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir and telithromycin), do not use STENDRA. Combination with Other PDE5 Inhibitors or Erectile Dysfunction Therapies is not recommended. The safety of STENDRA is unknown in patients with bleeding disorders and patients with active peptic ulceration. The use of STENDRA offers no protection against sexually transmitted diseases including HIV. Consider counseling patients on protective measures for sexually transmitted diseases. The most common adverse reactions reported with use of STENDRA include headache, flushing, nasal congestion, nasopharyngitis, and back pain. For more information about STENDRA, call 844-458-4887. If you would like to report an adverse event or product complaint, please contact us at 844-458-4887. You are encouraged to report negative side effects of prescription drugs to the FDA by calling 1-800-FDA-1088, or at . Please see the full Prescribing Information and Patient Information. Cautionary Note Regarding Forward-Looking Statements This press release includes forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. These forward-looking statements are based upon Petros Pharmaceuticals, Inc.'s ("Petros," "we," "our," "us" or the "Company") management's assumptions, expectations, projections, intentions, and beliefs about future events. In some cases, predictive, future-tense or forward-looking words such as "intend," "develop," "goal," "plan," "predict", "may," "will," "project," "estimate," "anticipate," "believe," "expect," "continue," "potential," "opportunity," "forecast," "should," "target," "strategy" and similar expressions, whether in the negative or affirmative, that reflect our current views with respect to future events and operational, economic and financial performance are intended to identify forward-looking statements, but are not the exclusive means of identifying such statements. Such forward-looking statements are only predictions, and actual results and the timing of certain events and circumstances may differ materially from those described by the forward-looking statements as a result of risks and uncertainties, Petros' ability to execute on its business strategy, including its plans to develop and commercialize its product candidates; Petros' ability to comply with obligations as a public reporting company; Petros' ability to maintain compliance with the Nasdaq Stock Market's listing standards; risks related to Petros' ability to continue as a going concern; risks related to Petros' history of incurring significant losses; risks related to Petros' dependence on the commercialization of a single product, STENDRA®; and risks related to Petros' ability to obtain regulatory approvals for, or market acceptance of, any of its products or product candidates. Additional factors that could cause actual results to differ materially from the results anticipated in these forward-looking statements are contained in the Company's periodic reports and in other filings that the Company has or may file, with the U.S. Securities and Exchange Commission (the "SEC") under the headings "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations" and elsewhere. The Company cautions readers that the forward-looking statements included in this press release represent our beliefs, expectations, estimates and assumptions only as of the date of hereof and are not intended to give any assurance as to future results. New factors emerge from time to time, and it is not possible for us to predict all these factors. Further, the Company cannot assess the effect of each such factor on our business or the extent to which any factor, or combination of factors, may cause actual results to be materially different from those contained in any forward-looking statement. Accordingly, you should not unduly rely on any forward-looking statements. The Company undertakes no obligation to update or revise any forward-looking statements contained in this press release, whether as a result of new information, future events, a change in our views or expectations or otherwise, except as required by federal securities laws. Contacts Investors: CORE IR ir@petrospharma.com Media: Jules Abraham CORE IR 917-885-7378 pr@coreir.com SOURCE: Petros Pharmaceuticals, Inc. View the original press release on accesswire.com