Cellulitis

Like most health systems across the United States, Pinehurst, North Carolina-based FirstHealth of the Carolinas has challenges with bed capacity and is always working on new and innovative ways to increase it in a safe and financially responsible way. THE PROBLEM This has been done through a few different venues. FirstHealth's extended care unit at its Richmond campus, among others, is a brick-and-mortar solution, whereas the observation at home (OAH) program helps with capacity challenges, but virtually. PROPOSAL The OAH program is designed to help increase bed capacity across the health system by discharging stable patients who can be managed at home via the program but would otherwise need to have stayed in the hospital if taken care of by traditional medicine. OAH offers multiple entities in the health system an alternative for some of the more stable patients occupying a bed. Once patients are referred to the program, a paramedic will visit them in their home the next day – exceptions are referrals from home health , which I will explain in a moment – where they will perform an in-person assessment that includes vital signs. Once the assessment is complete, the paramedic connects to a provider to complete the remainder of the visit via secure tele-video. FirstHealth uses Epic for these sessions. While the paramedic is present in the patient's home, the provider assesses the patient by tele-video and includes input from the paramedic to continue the patient's care. During the visit, the provider can order medications or labs. Of note, the paramedics do not use an ambulance for this program. The provider also will determine if the patient should be seen again, or if they are stable enough to be discharged from the program. The purpose of the OAH program is to help patients get over the acute phase of their illness. The average length of stay in the program is just over three days. After being released from the OAH program, patients already enrolled in home health will continue those visits. If the patient is not enrolled in home health, they will be transitioned to the virtual care at home program (VCAH). This program uses remote patient monitoring using devices from Health Recovery Solutions so staff can follow the patient's vital signs for the next few days and up to a couple of weeks. Patients also have access to a registered nurse via telephone if needed while in the VCAH. The VCAH program is provided at no cost to the patient and is part of a larger effort to help manage bed capacity. Staff see patients with the following diagnoses but can evaluate others on a case-by-case basis: CHF, COPD, pneumonia, influenza, COVID19, asthma, need for IV antibiotics, cellulitis rechecks and abdominal pain rechecks. Patients can be referred to OAH in a variety of manners: Inpatient referrals. Stable patients are referred to OAH by the hospitalist team. These are patients who remain stable and are enrolled into the OAH program to continue the remaining few days of care that would traditionally have been completed in a hospital bed. Emergency department referrals. Stable patients who would have traditionally been admitted to an in-hospital observation unit for a variety of reasons can now be discharged into the OAH program. Home health. Patients enrolled in home health who may have an acute issue arise. These are stable patients, but who normally would have been referred to the ED for further workup or treatment. Approximately 80% of patients sent to the ED by home health are admitted for observation. OAH is now an option for home health for their stable patients to be seen instead of having to send them to the ED. Patients with potential dangerous cardiac, pulmonary, neurological or other potentially unstable complaints are still sent to the ED immediately via 911. Patients typically seen in OAH from referrals by home health tend to be early onset COPD exacerbation, patients with CHF who have weight gain or increased shortness of breath but are not in respiratory distress, or patients with an upper respiratory infection who need further evaluation. For these patients, staff can intervene at an early stage of an exacerbation and help to keep the patient from needing to go to the ED. Patients referred to OAH are typically seen the same day as the referral. Primary care providers or convenient care providers. PCP or convenient care providers can also refer patients to OAH, where they are seen the next day, and assure their plan of care is effective and the patient is improving, but also to continue to provide care they may not have otherwise received unless being sent to the ER. The main referrals staff see from PCP and convenient care are COPD exacerbations and acute respiratory infections such as COVID-19, influenza or pneumonia in at-risk populations. MEETING THE CHALLENGE "We complete our telemedicine video visits using the Epic EHR," said Stephen Kapa, administrative director of telehealth services at FirstHealth of the Carolinas. "All information is relayed through that platform. For the patients who transition to the VCAH program, we use Health Recovery Solutions blood pressure cuffs and pulse oximeters. The patients download an app from the vendor on their phone and can upload their readings from their monitoring devices through the app. "A nurse monitors those daily and calls patients directly if someone has vital signs out of range," he continued. "Patients can also call the nurse directly with any concerns. Occasionally, we need to initiate a tele-video visit where patients are either re-enrolled into the OAH program or advised to go to the ED." FirstHealth has found keeping things as simple as possible is the best strategy, and that has worked since the COVID-19 pandemic. Too often, the more complicated things are made, the clunkier they become, resulting in more steps that are less likely to be used – keep things simple, Kapa added. RESULTS "One of our biggest achievements in the past 14 months has to be the average daily census in the program," Kapa reported. "Our fiscal year runs from October to October. In the first week of October of 2023, our average daily census was under two. We have had our peaks and troughs over the year, but the trend line has always been positive. In the last week of our fiscal year, we averaged 13 patients per day. "This has had a significant impact contributing to increased patient access and bed capacity as well as increased patient satisfaction and employee engagement," he continued. "We expect the average daily census to continue to climb, especially with the normal increase in volume of patients during the winter months." Another success that staff are quite happy with is their 30-day readmission rate for heart failure and for all-causes. "The average national 30-day readmission rate for heart failure and all-cause readmissions is approximately 20% and 14.5%, respectively," Kapa noted. "For patients admitted to the OAH program, the percentage for both heart failure and all-cause readmissions is under 10%. While this does represent a cost savings, more importantly it shows we can safely and effectively take care of patients with the OAH program. "Lastly, a subjective measure we really can't keep track of is the appreciation of patients and family who are thankful to receive their care safely at home instead of having to be admitted to the hospital," he added. "We have had so many words of thanks and gratitude for what this program has done to help them be where they are most comfortable – at home." ADVICE FOR OTHERS "My advice is twofold," Kapa said. "Keep things as simple as possible and be persistent. As you can see by the growth of our average daily census, it didn't grow overnight nor on its own. You need to be very persistent in delivering your message about the program to all groups, especially providers and discharge planners. "From a provider's perspective, many have been practicing medicine for some time," he continued. "They are used to doing things in a regimented and traditional fashion. I'm a physician assistant by training, so I understand this. Giving them the option of the OAH program gives them another option that hasn't traditionally been there. All you need is to be persistent and share the success stories. Share the data, as sparse as it may be in the beginning." And go to all of the provider meetings possible, he added. "Go to the discharge planner meetings, go to interdisciplinary rounds, speak about the program anywhere you can," he concluded. "Once the providers start to see the benefits of the program, see that their patients are being taken care of safely and see the readmission rates dropping, this will take on a life of its own. I'm hoping we are in this latter stage now." Follow Bill's HIT coverage on LinkedIn: Bill Siwicki Email him: bsiwicki@himss.org Healthcare IT News is a HIMSS Media publication.

Approval of SELARSDI 130 mg/26 mL in a single-dose vial for intravenous infusion expands label to include treatment of adults with Crohn’s disease and ulcerative colitis The FDA previously approved SELARSDI 45 mg/0.5 mL and 90 mg/mL in a single-dose prefilled syringe for subcutaneous injection in April 2024SELARSDI’s U.S. launch for all indications is expected in Q1 2025 REYKJAVIK, Iceland & PARSIPPANY, N.J., Oct. 22, 2024 (GLOBE NEWSWIRE) -- Alvotech (NASDAQ: ALVO) and Teva Pharmaceuticals, a U.S. affiliate of Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA), today announced that the U.S. Food and Drug Administration (FDA) has approved SELARSDI (ustekinumab-aekn) in a new presentation, 130 mg/26 mL (5 mg/mL) solution in a single-dose vial for intravenous infusion. This approval paves the way for SELARSDI to further align its label with the indications of the reference product Stelara® (ustekinumab) in the U.S. at launch, which is expected in the first quarter of 2025. “We welcome this step which is fully in line with our plan to align the SELARSDI label with the indications of the reference product, prior to launch next year,” said Robert Wessman, Chairman and CEO of Alvotech. “We are looking forward to the U.S. launch, after very successful launches of the first biosimilar ustekinumab in Canada, Japan and Europe. This demonstrates our commitment to increasing availability and access to ustekinumab, and other biosimilars in our growing pipeline, for patients worldwide.” “We are thrilled with the expansion of SELARSDI's indications, marking another significant milestone in Teva’s commitment to increasing access to biosimilars in the U.S.,” said Thomas Rainey, Senior Vice President, U.S. Biosimilars. “This development allows us to serve patients battling gastrointestinal diseases as the U.S. launch of SELARSDI approaches in early 2025. Teva’s dedication to increasing uptake of biosimilars remains steadfast, and we are proud to continue this partnership with Alvotech across a portfolio of nine partnered products.” In April 2024, the FDA approved SELARSDI 45 mg/0.5 mL and 90 mg/mL injection in a prefilled syringe for subcutaneous use, for the treatment of moderate to severe plaque psoriasis and for active psoriatic arthritis in adults and pediatric patients 6 years and older. In June 2023, Alvotech and Teva announced that they had reached a settlement and license agreement with the manufacturer of the reference biologic, granting a license entry date for SELARSDI in the United States no later than February 21, 2025. Alvotech developed and produces SELARSDI using Sp2/0 cells and a continuous perfusion process, which are the same type of host cell line and process used in the production of the reference product Stelara.1 Ustekinumab is a human monoclonal antibody that selectively targets the p40 protein, a component common to both interleukin (IL)-12 and IL-23 cytokines, which play crucial roles in treating immune-mediated diseases like psoriasis, psoriatic arthritis, ulcerative colitis and Crohn’s disease. In August 2020, Alvotech and Teva entered into a strategic partnership for the exclusive commercialization of five of Alvotech’s biosimilar product candidates, including SELARSDI. The partnership has since expanded and now includes a total of nine products. Alvotech handles development and manufacturing using its purpose-built end-to-end platform, while Teva is responsible for commercialization in the U.S., which leverages Teva’s experience and extensive sales and marketing infrastructure. Two biosimilars developed under the partnership have been given FDA approval: SELARSDI, and in February 2024, the FDA approved SIMLANDI® (adalimumab-ryvk), the first high-concentration, citrate-free interchangeable biosimilar to Humira® (adalimumab). SIMLANDI was launched in the U.S. in May 2024. About SIMLANDI® (adalimumab-ryvk) SIMLANDI is a monoclonal antibody and has been approved as a biosimilar to Humira® (adalimumab) in over 50 countries globally, including the U.S., Europe, Canada, Australia, Egypt, Saudi Arabia and South Africa. The biosimilar is currently marketed in the U.S. as SIMLANDI and under private label as adalimumab-ryvk, in Europe as HUKYNDRA, in Canada as SIMLANDI and in Australia as ADALACIP. Applications are also under review in multiple countries globally. About SELARSDI™ (ustekinumab-aekn) SELARSDI is a monoclonal antibody and a biosimilar to Stelara® (ustekinumab). Ustekinumab binds to two cytokines, IL-12 and IL-23, that are involved in inflammatory and immune responses.2 The biosimilar has been launched in Canada as JAMTEKI, in Europe as UZPRUVO and in Japan as USTEKINUMAB BS (F). It has been approved in the U.S. as SELARSDI. Applications are also under review in multiple countries globally. Use of TrademarksStelara® is a registered trademark of Johnson & Johnson. Humira® is a registered trademark of AbbVie Biotechnology Ltd. About AlvotechAlvotech is a biotech company, founded by Robert Wessman, focused solely on the development and manufacture of biosimilar medicines for patients worldwide. Alvotech seeks to be a global leader in the biosimilar space by delivering high quality, cost-effective products, and services, enabled by a fully integrated approach and broad in-house capabilities. Two biosimilars to Humira® (adalimumab) and Stelara® (ustekinumab) are already approved and marketed in multiple global markets. The current development pipeline includes nine disclosed biosimilar candidates aimed at treating autoimmune disorders, eye disorders, osteoporosis, respiratory disease, and cancer. Alvotech has formed a network of strategic commercial partnerships to provide global reach and leverage local expertise in markets that include the United States, Europe, Japan, China, and other Asian countries and large parts of South America, Africa, and the Middle East. Alvotech’s commercial partners include Teva Pharmaceuticals, a US affiliate of Teva Pharmaceutical Industries Ltd. (US), STADA Arzneimittel AG (EU), Fuji Pharma Co., Ltd (Japan), Advanz Pharma (EEA, UK, Switzerland, Canada, Australia and New Zealand), Dr. Reddy’s (EEA, UK and US), Biogaran (FR), Cipla/Cipla Gulf/Cipla Med Pro (Australia, New Zealand, South Africa/Africa), JAMP Pharma Corporation (Canada), Yangtze River Pharmaceutical (Group) Co., Ltd. (China), DKSH (Taiwan, Hong Kong, Cambodia, Malaysia, Singapore, Indonesia, India, Bangladesh and Pakistan), YAS Holding LLC (Middle East and North Africa), Abdi Ibrahim (Turkey), Kamada Ltd. (Israel), Mega Labs, Stein, Libbs, Tuteur and Saval (Latin America) and Lotus Pharmaceuticals Co., Ltd. (Thailand, Vietnam, Philippines, and South Korea). Each commercial partnership covers a unique set of product(s) and territories. Except as specifically set forth therein, Alvotech disclaims responsibility for the content of periodic filings, disclosures and other reports made available by its partners. For more information, please visit https://www.alvotech.com. None of the information on the Alvotech website shall be deemed part of this press release. For more information, please visit our investor portal, and our website or follow us on social media on LinkedIn, Facebook, Instagram, X and YouTube. About TevaTeva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA) is a global pharmaceutical leader with a category-defying portfolio, harnessing our generics expertise and stepping up innovation to continue the momentum behind the discovery, delivery, and expanded development of modern medicine. For over 120 years, Teva's commitment to bettering health has never wavered. Today, the company’s global network of capabilities enables its 37,000 employees across 58 markets to push the boundaries of scientific innovation and deliver quality medicines to help improve health outcomes of millions of patients every day. To learn more about how Teva is all in for better health, visit www.tevapharm.com. SELARSDI INDICATIONS AND SAFETY INFORMATION INDICATIONS SELARSDI™ (ustekinumab-aekn) Injection, is a human interleukin-12 and -23 antagonist indicated for:• the treatment of adults and pediatric patients 6 years of age and older with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy. • the treatment of adults and pediatric patients 6 years of age and older with active psoriatic arthritis.• the treatment of adult patients with moderately to severely active Crohn's disease.• the treatment of adult patients with moderately to severely active ulcerative colitis. IMPORTANT SAFETY INFORMATION SELARSDI™ (ustekinumab-aekn) injection is contraindicated in patients with clinically significant hypersensitivity to ustekinumab products or to any of the excipients in SELARSDI. InfectionsUstekinumab products may increase the risk of infections and reactivation of latent infections. Serious bacterial, mycobacterial, fungal, and viral infections were observed in patients receiving ustekinumab products. Serious infections requiring hospitalization or otherwise clinically significant infections were reported. In patients with plaque psoriasis, these included diverticulitis, cellulitis, pneumonia, appendicitis, cholecystitis, sepsis, osteomyelitis, viral infections, gastroenteritis, and urinary tract infections. In patients with psoriatic arthritis, this included cholecystitis. In patients with Crohn’s disease, these included anal abscess, gastroenteritis, ophthalmic herpes zoster, pneumonia, and Listeria meningitis. In patients with ulcerative colitis, these included gastroenteritis, ophthalmic herpes zoster, pneumonia, and listeriosis. Treatment with SELARSDI should not be initiated in patients with a clinically important active infection until the infection resolves or is adequately treated. Consider the risks and benefits of treatment prior to initiating use of SELARSDI in patients with a chronic infection or a history of recurrent infection. Instruct patients to seek medical advice if signs or symptoms suggestive of an infection occur while on treatment with SELARSDI and discontinue SELARSDI for serious or clinically significant infections until the infection resolves or is adequately treated. Theoretical Risk for Vulnerability to Particular InfectionsIndividuals genetically deficient in IL-12/IL-23 are particularly vulnerable to disseminated infections from mycobacteria (including nontuberculous, environmental mycobacteria), Salmonella (including nontyphi strains), and Bacillus Calmette-Guerin (BCG) vaccinations. Serious infections and fatal outcomes have been reported in such patients. It is not known whether patients with pharmacologic blockade of IL-12/IL-23 from treatment with ustekinumab products may be susceptible to these types of infections. Consider diagnostic testing, e.g., tissue culture, stool culture, as dictated by clinical circumstances. Pre-Treatment Evaluation of Tuberculosis (TB)Evaluate patients for TB prior to initiating treatment with SELARSDI. Do not administer SELARSDI to patients with active TB infection. Initiate treatment of latent TB before administering SELARSDI. Consider anti-tuberculosis therapy prior to initiation of SELARSDI in patients with a history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Closely monitor patients receiving SELARSDI for signs and symptoms of active TB during and after treatment. MalignanciesUstekinumab products are immunosuppressants and may increase the risk of malignancy. Malignancies were reported among patients who received ustekinumab in clinical trials. The safety of ustekinumab products has not been evaluated in patients who have a history of malignancy or who have a known malignancy. There have been post-marketing reports of the rapid appearance of multiple cutaneous squamous cell carcinomas in patients receiving ustekinumab products who had pre-existing risk factors for developing non-melanoma skin cancer (NMSC). All patients receiving SELARSDI, especially those greater than 60 years of age or those with a history of Psoralen plus ultraviolet A (PUVA) or prolonged immunosuppressant treatment, should be monitored for the appearance of NMSC. Hypersensitivity ReactionsHypersensitivity reactions, including anaphylaxis and angioedema, have been reported with ustekinumab products. If an anaphylactic or other clinically significant hypersensitivity reaction occurs, institute appropriate therapy and discontinue SELARSDI. Posterior Reversible Encephalopathy Syndrome (PRES)Two cases of posterior reversible encephalopathy syndrome (PRES), also known as Reversible Posterior Leukoencephalopathy Syndrome (RPLS), were reported in clinical trials. Cases have also been reported in postmarketing experience in patients with psoriasis, psoriatic arthritis, and Crohn’s disease. Clinical presentation included headaches, seizures, confusion, visual disturbances, and imaging changes consistent with PRES a few days to several months after ustekinumab product initiation. A few cases reported latency of a year or longer. Patients recovered with supportive care following withdrawal of ustekinumab products. Monitor all patients treated with SELARSDI for signs and symptoms of PRES. If PRES is suspected, promptly administer appropriate treatment and discontinue SELARSDI. ImmunizationsPrior to initiating therapy with SELARSDI, patients should receive all age-appropriate immunizations as recommended by current immunization guidelines. Patients being treated with SELARSDI should not receive live vaccines. Avoid administering BCG vaccines during treatment with SELARSDI or for one year prior to initiating treatment or one year following discontinuation of treatment. Caution is advised when administering live vaccines to household contacts of patients receiving SELARSDI because of the potential risk for shedding from the household contact and transmission to patient. Non-live vaccinations received during a course of SELARSDI may not elicit an immune response sufficient to prevent disease. Concomitant TherapiesThe safety of ustekinumab products, in combination with other biologic immunosuppressive agents or phototherapy has not been evaluated in clinical trials of psoriasis. Ultraviolet-induced skin cancers developed earlier and more frequently in mice. In psoriasis studies, the relevance of findings in mouse models for malignancy risk in humans is unknown. In psoriatic arthritis studies, concomitant methotrexate use did not appear to influence the safety or efficacy of ustekinumab. Noninfectious PneumoniaCases of interstitial pneumonia, eosinophilic pneumonia, and cryptogenic organizing pneumonia have been reported during post-approval use of ustekinumab products. Clinical presentations included cough, dyspnea, and interstitial infiltrates following one to three doses. Serious outcomes have included respiratory failure and prolonged hospitalization. Patients improved with discontinuation of therapy and, in certain cases, administration of corticosteroids. If diagnosis is confirmed, discontinue SELARSDI and institute appropriate treatment. Allergen ImmunotherapyUstekinumab products have not been evaluated in patients who have undergone allergy immunotherapy. Ustekinumab products may decrease the protective effect of allergen immunotherapy (decrease tolerance) which may increase the risk of an allergic reaction to a dose of allergen immunotherapy. Therefore, caution should be exercised in patients receiving or who have received allergen immunotherapy, particularly for anaphylaxis. Most Common Adverse ReactionsThe most common adverse reactions for plaque psoriasis (greater than or equal to 3%) were nasopharyngitis, upper respiratory tract infection, headache, and fatigue. The safety profile in pediatric patients with plaque psoriasis was similar to that of adults with plaque psoriasis. The most common adverse reaction for Crohn's disease induction (greater than or equal to 3%) was vomiting. The most common adverse reactions for Crohn's disease maintenance (greater than or equal to 3%) were nasopharyngitis, injection site erythema, vulvovaginal candidiasis/mycotic infection, bronchitis, pruritus, urinary tract infection, and sinusitis. The most common adverse reaction for ulcerative colitis induction (greater than or equal to 3%) was nasopharyngitis. The most common adverse reactions for ulcerative colitis maintenance (greater than or equal to 3%) were nasopharyngitis, headache, abdominal pain, influenza, fever, diarrhea, sinusitis, fatigue, and nausea. Please click here for full Prescribing Information for SELARSDI. Alvotech Forward Looking StatementsCertain statements in this communication may be considered “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements generally relate to future events or the future financial operating performance of Alvotech and may include, for example, Alvotech’s expectations regarding competitive advantages, business prospects and opportunities including pipeline product development, future plans and intentions, results, level of activities, performance, goals or achievements or other future events, regulatory submissions, review and interactions, the potential approval and commercial launch of its product candidates, the timing of regulatory approval, and market launches. In some cases, you can identify forward-looking statements by terminology such as “may”, “should”, “expect”, “intend”, “will”, “estimate”, “anticipate”, “believe”, “predict”, “potential”, “aim”, or “continue”, or the negatives of these terms or variations of them or similar terminology. Such forward-looking statements are subject to risks, uncertainties, and other factors which could cause actual results to differ materially from those expressed or implied by such forward-looking statements. These forward-looking statements are based upon estimates and assumptions that, while considered reasonable by Alvotech and its management, are inherently uncertain and are inherently subject to risks, variability, and contingencies, many of which are beyond Alvotech’s control. Factors that may cause actual results to differ materially from current expectations include, but are not limited to: (1) the ability to raise substantial additional funding, which may not be available on acceptable terms or at all; (2) the ability to maintain stock exchange listing standards; (3) changes in applicable laws or regulations; (4) the possibility that Alvotech may be adversely affected by other economic, business, and/or competitive factors; (5) Alvotech’s estimates of expenses and profitability; (6) Alvotech’s ability to develop, manufacture and commercialize the products and product candidates in its pipeline; (7) actions of regulatory authorities, which may affect the initiation, timing and progress of clinical studies or future regulatory approvals or marketing authorizations; (8) the ability of Alvotech or its partners to respond to inspection findings and resolve deficiencies to the satisfaction of the regulators; (9) the ability of Alvotech or its partners to enroll and retain patients in clinical studies; (10) the ability of Alvotech or its partners to gain approval from regulators for planned clinical studies, study plans or sites; (11) the ability of Alvotech’s partners to conduct, supervise and monitor existing and potential future clinical studies, which may impact development timelines and plans; (12) Alvotech’s ability to obtain and maintain regulatory approval or authorizations of its products, including the timing or likelihood of expansion into additional markets or geographies; (13) the success of Alvotech’s current and future collaborations, joint ventures, partnerships or licensing arrangements; (14) Alvotech’s ability, and that of its commercial partners, to execute their commercialization strategy for approved products; (15) Alvotech’s ability to manufacture sufficient commercial supply of its approved products; (16) the outcome of ongoing and future litigation regarding Alvotech’s products and product candidates; (17) the impact of worsening macroeconomic conditions, including rising inflation and interest rates and general market conditions, conflicts in Ukraine, the Middle East and other global geopolitical tension, on the Company’s business, financial position, strategy and anticipated milestones; and (18) other risks and uncertainties set forth in the sections entitled “Risk Factors” and “Cautionary Note Regarding Forward-Looking Statements” in documents that Alvotech may from time to time file or furnish with the SEC. There may be additional risks that Alvotech does not presently know or that Alvotech currently believes are immaterial that could also cause actual results to differ from those contained in the forward-looking statements. Nothing in this communication should be regarded as a representation by any person that the forward-looking statements set forth herein will be achieved or that any of the contemplated results of such forward-looking statements will be achieved. You should not place undue reliance on forward-looking statements, which speak only as of the date they are made. Alvotech does not undertake any duty to update these forward-looking statements or to inform the recipient of any matters of which any of them becomes aware of which may affect any matter referred to in this communication. Alvotech disclaims any and all liability for any loss or damage (whether foreseeable or not) suffered or incurred by any person or entity as a result of anything contained or omitted from this communication and such liability is expressly disclaimed. The recipient agrees that it shall not seek to sue or otherwise hold Alvotech or any of its directors, officers, employees, affiliates, agents, advisors, or representatives liable in any respect for the provision of this communication, the information contained in this communication, or the omission of any information from this communication. Teva Cautionary Note Regarding Forward Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, which are based on management’s current beliefs and expectations and are subject to substantial risks and uncertainties, both known and unknown, that could cause our future results, performance or achievements to differ significantly from that expressed or implied by such forward-looking statements. You can identify these forward-looking statements by the use of words such as “should,” “expect,” “anticipate,” “estimate,” “target,” “may,” “project,” “guidance,” “intend,” “plan,” “believe”, and other words and terms of similar meaning and expression in connection with any discussion of future operating or financial performance. Important factors that could cause or contribute to such differences include risks relating to: our strategic partnership with Alvotech; our ability to successfully develop and commercialize SELARSDI in the U.S.; our ability to successfully commercialize SIMLANDI in the U.S; our ability to commercialize the additional biosimilar product candidates under the strategic partnership with Alvotech once U.S. regulatory approval is obtained; our ability to successfully compete in the marketplace including our ability to develop and commercialize additional pharmaceutical products; our ability to successfully execute our Pivot to Growth strategy, including to expand our innovative and biosimilar medicines pipeline and profitably commercialize the innovative medicines and biosimilar portfolio, whether organically or through business development, and to sustain and focus our portfolio of generics medicines; and other factors discussed in this press release, in our Quarterly Report on Form 10-Q for the second quarter of 2024 and in our Annual Report on Form 10-K for the year ended December 31, 2023, including in the sections captioned “Risk Factors.” Forward-looking statements speak only as of the date on which they are made, and we assume no obligation to update or revise any forward-looking statements or other information contained herein, whether as a result of new information, future events or otherwise. You are cautioned not to put undue reliance on these forward-looking statements.Sources Stelara FDA product label. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/761044s013lbl.pdf. Accessed on October 18, 2024.Selarsdi FDA product label. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/761343s000lbl.pdf. Accessed on October 18, 2024. Contacts for the Media and Investor Relations Alvotech IR and PRBenedikt Stefansson, VPalvotech.ir@alvotech.com Teva IR Contacts Ran Meir +1 (267) 468 4475 Yael Ashman +972 (3) 914 8262 Sanjeev Sharma +1 (973) 658 2700 PR Contacts Kelley Dougherty +1 (973) 832-2810 Yonatan Beker +1 (973) 264-7378 Eden Klein +972 (3) 906 2645

在这篇文章中，我们将继续尝试探讨，在药物开发过程中相对常见的，与原适应症类型不同的新适应症类型，在进行相应专利申请时可能需要重点关注的方面。 与原适应症类型不同的“新适应症”专利保护 by TiPLab MM 在本系列文章的序中，我们根据拓展的新适应症类型与现有药物原适应症之间的关系，将拓展的新适应症分为两类：1) 新适应症类型与原适应症类型不同；2) 新适应症是原适应症类型的下位概念。在本篇文章中，我们将进一步展开 “与原适应症类型不同的新适应症类型”的研究内容。相对于“原适应症类型的下位概念”而言，本篇文章中所指的“类型不同”，包括不属于原适应症下位概念的“新适应症”。 对于同一药物活性分子，开发与原适应症类型不同的新适应症，一种理想的情境是传统意义上的“老药新用”，即新适应症类型是基于药物活性分子的全新作用机制拓展的，由于与药物用于治疗原适应症的机制存在显著差异，这类发现在进行专利保护时，创造性问题通常比较容易克服。 但随着科学技术的进步，对于各种疾病的机理及药物作用过程的研究更加深入，在实际研发过程中，如果新适应症的拓展围绕活性分子已知的功能和机制展开，即使新适应症类型与原适应症不同，往往仍会被认为其治疗作用是本领域技术人员可以合理预期的，给专利保护带来创造性的挑战。 如果药物活性分子已经公开，而现有技术中已经披露了具有相同或类似生物活性的分子用于治疗该“新适应症”的技术方案，例如对同一靶点具有特异性但结构不同的活性分子治疗该适应症的相关披露，即使现有技术中未提供具体的疗效数据，这种公开也会被视为提供了足够的技术启示，使得治疗效果成为合理可预期的结果。 例如，申请人为诺华股份有限公司，请求保护IL-1β抗体卡那奴单抗（ACZ885）用于治疗新适应症的专利申请（申请号CN201510324201.1），就由于创造性问题经历了两次驳回。第一次驳回 该申请首次被驳回的权利要求1请求保护IL-1β单克隆抗体ACZ885用于治疗肿瘤坏死因子受体相关周期性综合征（TRAPS）、过度免疫球蛋白D综合征（HIDS）和成人发作性斯蒂尔病（AOSD）。 图1 CN201510324201.1 第一次被驳回的权利要求1 对比文件1（WO2007050607A2）是申请人同为诺华的在先申请，其中记载了ACZ885的序列、IL-1β抗体用于治疗IL-1β介导的疾病和病症，并且记载了临床试验表明Muckle-Wells综合征患者接受单剂量的ACZ885输注10mg/kg处理后，症状得到改善的数据。对比文件2（WO2007002261A2）是涉及其他IL-1β抗体的专利申请，其公开了用IL-1β抗体治疗相关疾病，包括TRAPS。 其首次被驳回的主要理由是，权利要求1中涉及TRAPS的技术方案与对比文件1公开的技术方案相比，区别仅在于所治疗的疾病不同。虽然对比文件2中没有使用具体实施例验证IL-1β抗体治疗TRAPS的效果，但已经提供了足够的技术启示。本领域技术人员容易想到将对比文件1公开的IL-1β单克隆抗体ACZ885用于治疗TRAPS，且效果可以预期。第二次驳回 在复审阶段，请求人删除了权利要求1中涉及TRAPS的技术方案，合议组撤回了驳回决定后，国知局基于复审答复修改后的权利要求继续审查，在下发了2次审查意见通知书后，于2024年6月12日发出了第二次驳回决定。 图2 CN201510324201.1 第二次被驳回的权利要求1 申请人在复审修改后的权利要求1中请求保护ACZ885用于治疗HIDS和AOSD的技术方案，在审查过程中，审查员进一步引用了记载IL-1β与HIDS和AOSD相关的对比文件3和对比文件4，其分别披露了对于IL-1β有拮抗作用的IL-1拮抗剂阿那白滞素（Anakinra）对于HIDS、AOSD可能具有治疗益处，并且明确指出了IL-1β是可能的靶点，因此审查员认为本申请的IL-1β抗体对于HIDS、AOSD的治疗效果是显而易见的，不具备创造性。 虽然申请人主张其抗体具备更长的半衰期，并取得了预料不到的技术效果，但由于抗体ACZ885是已知抗体，其具备更长的半衰期效果是抗体分子所固有的属性，并非该抗体应用于新适应症所特有的效果，因此在对比文件3和对比文件4公开内容的影响下，申请人拟保护“新适应症HIDS、AOSD”受到了创造性问题的挑战。TiPLab小贴士 该申请目前经历2次驳回，不排除可能的原因还在于申请文件中并未记载ACZ885用于治疗TRAPS、HIDS和AOSD相对应的实验数据，在争辩时存在挑战；但即使其记载了相应数据，由于已有具有同样功能的分子治疗作用或相关机制报道，仅借由药物活性分子的固有属性带来的差异，很有可能依旧不足以建立发明方案的创造性。由此可见，单独申请仅保护这类新适应症的治疗用途专利在中国存在一定挑战。 因此，在尝试保护“与原适应症类型不同的新适应症”方案时，对于上述情况中所面临的创造性问题： 一方面，我们建议在新适应症用途发明的申请布局前，充分调研披露相关/类似分子及其作用机理的现有技术，提前做好创造性问题的预期与判断，针对性地进行说明书权利要求的撰写及相关数据的准备工作。如果存在相关的现有技术，在撰写时应详细阐述为什么对于该新适应症的治疗效果是无法合理预期的。 另一方面，以用途作为发明点的申请中，建议提供更为充分的数据，相关效果需要体现在活性分子的固有属性之外，并且最好能够建立与新适应症的“特有关系”，此外，还需体现在对于新适应症的治疗效果具备“预料不到”的优异性，例如可以通过提供产品分子与同类分子的效果对比例，突出对于新适应症的治疗效果是难以合理预期的。 * 以上文字仅为促进讨论与交流，不构成法律意见或咨询建议。 © 作为一家专业服务公司，TiPLab坚持原创的系统的研究，注重系统性知识积累与专业影响力。欢迎读者个人分享转发，各专业平台媒体如需转载请联系TiPLab获得授权。  TiPLab提供基于研究的核心知识产权服务 FTO：技术商业化实施的侵权风险防范 TiPLab通过对细分技术领域内核心技术和重要专利的长期研究，结合自身在数据检索和分析方面的专长，致力于帮助客户深入了解、积极应对潜在的专利侵权风险。 Due Diligence：商业活动中的知识产权尽职调查 在企业许可交易、融资、并购、上市等过程中，TiPLab帮助企业和投资方了解目标技术/产品的专利保护强度及产品商业化过程中潜在的专利侵权风险，从而为商业谈判和决策提供支持依据。 Strategic Patenting：全球范围内高价值专利资产的创设 TiPLab熟知全球主要国家和地区的法律实践和细分领域内的前沿技术进展情况，通过前瞻性的专利布局策略，帮助客户通过创设有价值的专利资产而获取、保持和巩固独特的竞争优势。