The probability of cost-effectiveness for extended-pulsed fidaxomicin at a willingness-to-pay threshold of 30 000 (~USD 38 000) per QALY gained was 76% [26] and 99.9% at a threshold of 30 000 (~USD 35 000) per QALY gained [27]. No provision of this Section8 shall be given effect to the extent that such provision would cause any tax to become due under Section409A of the Code with regard to Incentive Awards subject to Section409A of the Code. Although fidaxomicin is orally administered and is generally well tolerated, the cost is prohibitive without adequate insurance coverage. A limited number of cost-effectiveness models have compared oral fidaxomicin 200 mg 2 times daily with oral vancomycin 125 mg 4 times daily for treatment of an initial CDI episode [2428]. Moreover, tax laws are often unclear and subject to a broad range of interpretations. No provision of this Section8 shall be given effect to the extent such provision would result in short-swing profits liability under Section16 of the Exchange Act or violate the exemptive conditions of Rule16b-3 of the Exchange Act. Dividend & shareholder information - South32 PDF Class Ruling Amcor Limited - scrip for scrip roll-over Is fidaxomicin worth the cost? 13. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. The Board of Directors may at any time suspend or discontinue the Plan or revise or amend it in any respect whatsoever; provided, however, that to the extent that any applicable law, tax requirement, or ruleof a stock exchange requires shareholder approval in order for any such revision or amendment to be effective, such revision or amendment shall not be effective without such approval. This content does not have an English version. Upon the death of a Participant, outstanding Incentive Awards granted to such Participant may be exercised only by the executors or administrators of the Participants estate or by any Person or Persons who shall have acquired such right to exercise by will or by the laws of descent and distribution. Clinical practice guidelines we can trust. Follow the topics, people and companies that matter to you. Randomized trials (with moderate quality of evidence) suggest that treatment with fresh or freeze-thawed donor FMT is more effective than treatment with vancomycin or autologous FMT. Comment:This recommendation places a high value in the beneficial effects and safety of fidaxomicin, but its implementation depends upon available resources. Subject to any action by the shareholders of the Company required by law, applicable tax rulesor the rulesof any exchange on which Shares are listed for trading: (a) Shares Available for Grants. The panel gave their strongest recommendation for considering the use of fecal microbiota transplant (FMT) in patients with at least two episodes of recurrent CDI after failure of antibiotics. (n) Eligible Person has the meaning set forth in Section5 of the Plan. Many of these functions can now be done . The panel agrees that the cost-effectiveness analysis favors the addition of bezlotoxumab to SOC antibiotics in patients with a recurrent CDI episode within the last 6 months but acknowledges that implementing this recommendation also probably reduces equity due to variation in medical insurance coverage. was selected by the IDSA Standards and Practice Guidelines Committee (SPGC). Fidaxomicin also has an advantage of twice-daily dosing, whereas vancomycin is administered 4 times daily. Lancet Infect Dis 2018; 18:2313. Notwithstanding anything herein to the contrary, Amcor shall not be obligated to cause to be issued Shares pursuant to the Plan unless and until Amcor is advised by its counsel that the issuance is in compliance with all applicable laws, regulations of governmental authority and the requirements of any securities exchange on which Shares are traded. The panels recommendations for the management CDI are based upon evidence derived from topic-specific systematic literature reviews. Like vancomycin, it is orally delivered with minimal systemic absorption and it is highly active againstC. difficilein vitro. (j) Company means Amcor and all of its Subsidiaries, collectively. Mayo Clinic Proceedings. GRADEpro guideline development tool [software]. Investors & Shareholders FAQ | Amcor Sirbu BD, Soriano MM, Manzo C, Lum J, Gerding DN, Johnson S. Vancomycin taper and pulse regimen with careful follow-up for patients with recurrent Clostridium difficile infection. The observed lower recurrence rates following fidaxomicin therapy as compared with vancomycin are an important advantage. Critical and important outcomes (presented in their respective Summary of Findings Tables [Tables 2,3and4]) were those that ultimately provided guidance on the optimal course of action. McDonald LC, et al. AMCOR Stock Forecast is based on your current time horizon. The panel labeled these as weak recommendations due to the fact that there are still limited data to guide treatment of a first recurrence," notes John K. DiBaise, M.D., from Mayo Clinic's campus in Arizona. "These two medications have demonstrated superior efficacy and reduced rates of adverse events when compared with metronidazole. (ii)Each Option shall be exercisable in whole or in part. They are assessments of current scientific and clinical information provided as an educational service; are not continually updated and may not reflect the most recent evidence (new evidence may emerge between the time information is developed and when it is published or read); should not be considered inclusive of all proper treatments, methods of care, or as a statement of the standard of care; do not mandate any particular course of medical care; and are not intended to supplant physician judgment with respect to particular patients or special clinical situations. (x) Registration Date means the effective date of the first registration statement that is filed by Amcor and declared effective pursuant to 12(g)of the Exchange Act, with respect to any class of Amcors securities. Indeed, this study provided the rationale for the extended-pulsed fidaxomicin regimen that was used by Guery et al [18]. Severability. Shareholder Dividends | Amcor Clinical practice guidelines for Clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Open Forum Infect Dis 2014; 1:ofu069. Mr Illingworth believes Amcor shareholders should be mindful of the precedent being set by Iron Mountain. V. L. has received past research funding from the Fonds de Recherche du Qubec Research (FRQ-S). Higgins JP, Altman DG, Gtzsche PC, et al; Cochrane Bias Methods Group; Cochrane Statistical Methods Group. Efficacy of alternative fidaxomicin dosing regimens for treatment of simulated Clostridium difficile infection in an in vitro human gut model. Published The panel suggests using bezlotoxumab as a co-intervention along with SOC antibiotics for patients with a recurrent CDI within the last 6 months to reduce the risk of a subsequent CDI recurrence after initial clinical cure. All studies compared fidaxomicin with a standard regimen of vancomycin (125 mg orally 4 times daily for 10 days). Louie TJ, Cannon K, Byrne B, et al. The use of fidaxomicin resulted in comparable CDI initial clinical cure (RR: 1.03; 95% CI: .941.14; low certainty evidence) but failed to show a reduction in all-cause mortality (RR: 0.81; 95% CI: .203.38; low certainty evidence). All members of the panel participated in the preparation of the draft guideline and approved the recommendations. No provision of this Section14 shall be given effect to the extent that such provision would cause any tax to become due under Section409A of the Code with regard to Incentive Awards subject to Section409A of the Code. Prevention of recurrent Clostridioides difficile infection: a systematic review of randomized controlled trials. Disclaimer. This effect was judged to be very uncertain due to the lack of stratification for these risk groups during randomization and the number of patients included in the subgroups. New Amcor share or CDI would be disregarded, except because of a roll-over (paragraph 124-795(2)(a)). The panel thanks Genet Demisashi and Rebecca Goldwater for their continued support throughout the guideline process. Consequences if scrip for scrip roll-over is chosen . Notwithstanding the foregoing, no Option shall be exercisable after the expiration of ten years from the date such Option is granted; provided, however that the expiration of the Option may be tolled while the Participant cannot exercise such Option because an exercise would violate an applicable law, or would jeopardize the ability of Amcor to continue as a going concern, provided, further that the period during which the Option may be exercised is not extended more than 30 days after the exercise of the Option first would no longer violate such applicable laws or jeopardize the ability of Amcor to continue as a going concern. Adv Ther 2018; 35:192034. AMCOR PLC CDI 1:1. Anaerobe 2020; 61:102098. This market value should be determined by reference to the last closing price of the shares on the Implementation Date, which was US$11.18 for Amcor plc share and AUD$16.00 for a CDI. Analysis of AMCOR PLC Simple Moving Average, A two period moving average forecast for AMCOR PLC is based on an daily price series in which the stock price on a given. Of the Shares described, 100% may be delivered in connection with full-value Awards, meaning Incentive Awards other than Options or stock appreciation rights. PDF Corporate - assets.ctfassets.net Using US cost estimates demonstrated similar results. Data obtained from a pooled analysis from two randomized trials demonstrate higher rates of clinical response in patients treated with vancomycin (81.1 percent) when compared with metronidazole (72.7 percent). This drug has several characteristics that make it an attractive therapy for CDI. AMCOR PLC CDI Price Forecast 2022 - Accumulation Distribution - Macroaxis For recommendations where the comparators are not formally stated, the comparison of interest is implicitly referred to as not using the intervention. Research Needs were noted for recommendations as deemed appropriate by the panel. In summary, a strong recommendation implies that most individuals in this situation would want the recommended course of action and only a small proportion would not, while a conditional recommendation means that the majority of individuals in this situation would want the suggested course of action but many would not. PDF Investor Briefing ", Amcor chief executive Ron Delia said Amcor shareholders have the choice of taking up the New York-listed shares or owning CDIs listed on the ASXPaul Jeffers. The overall certainty in the evidence was rated as low due to serious concerns regarding imprecision (small number of events and small sample size of these subgroups) as well as risk of bias due to the unblinded design in the EXTEND trial (for self-reported outcomes) (seeTable 3). Unlike vancomycin, there are no other treatment indications and it is a narrow spectrum agent with more limited activity against other enteric commensal bacteria [21]. As noted above, there is robust evidence supporting fidaxomicin treatment for patients with an initial episode of CDI. North American alcohol giant Constellation Brands took seven years to dump its Australian CDIs after its $1.9 billion takeover of BRL Hardy, which owned wine brands including Hardys, Leasingham and Banrock Station. (s) Option means a stock option to purchase Shares granted to a Participant pursuant to Section6. These new recommendations are also included in an updated table from the previous guidelines (seeTable 1, Recommendations for the Treatment ofClostridioides difficileInfection in Adults). been deferred, the Participant may, by written notice, withdraw such exercise and obtain the refund of any amount paid with respect thereto. Analysis of AMCOR PLC 8 Period Moving Average, An 8-period moving average forecast model for AMCOR PLC is based on an artificially constructed time series of AMCOR PLC. The exercise price per Share covered by any Option shall be not less than 100% of the Fair Market Value of a Share on the date on which such Option is granted, it being understood that the exercise price of an Option that is a Substitute Award may be less than the Fair Market Value per Share on the date such Substitute Award is assumed, provided that such substitution complies with applicable laws and regulations. (iii)for an Eligible Person who is a Consultant at the time of grant of an Incentive Award, the period during which such Eligible Person is providing services to the Company. The exercise or settlement of any Incentive Award (including, without limitation, any Option) granted hereunder shall only be effective unless at such time counsel to Amcor shall have determined that the issuance and delivery of Shares pursuant to such exercise would not be in compliance with all applicable laws, regulations of governmental authority and the requirements of any securities exchange on which Shares are traded. The Committee may from time to time grant Options on such terms as it shall determine, subject to the terms and conditions set forth in the Plan. Data on the use of bezlotoxumab when fidaxomicin is used as the SOC antibiotic are limited. It develops and produces flexible packaging, rigid containers, specialty cartons, closures and services for food, beverage, pharmaceutical, medical device, home and personal care and other products. An economic analysis. Clinical response rates achieved with fidaxomicin (88 percent) and vancomycin (86 percent) are similar. The pooled analysis of the 3 included subgroups demonstrates that fidaxomicin increased sustained response of CDI 30 days after end of therapy compared with vancomycin (RR: 1.27; 95% CI: 1.051.54; low certainty evidence), while the evidence failed to show a beneficial effect of fidaxomicin on sustained response at 90 days (RR: 1.56; 95% CI: .992.44; very low certainty evidence). All studies reported a similar rate of patients presenting with an initial episode of CDI (ranging from 79% to 86%) and with a comparable clinical severity on presentation (although definitions of severity differed between studies); the latter 2 studies restricted inclusion only to inpatients, in contrast with earlier studies where only 59% to 68% were hospitalized. Other Share-Based Awards and Cash-Based Awards, (a) Other Share-Based Awards. Gupta A, et al. Make your tax-deductible gift and be a part of the cutting-edge research and care that's changing medicine. Cohen SH, Gerding DN, Johnson S, et al; Society for Healthcare Epidemiology of America; Infectious Diseases Society of America. For the avoidance of doubt, the Committee may exercise all discretion granted to it under the Plan in a non-uniform manner among Participants. Extended-pulsed fidaxomicin versus vancomycin in patients 60 years and older with Clostridium difficile infection: cost-effectiveness analysis in Spain. Amcor's corporate code of conduct and ethics policy is available in 23 languages in addition to English. Drug-resistant E. coli bacteremia transmitted by fecal microbiota transplant. PLoS One 2016; 11:e0149521. Initial U.S. approval: 2016. Fidaxomicin preserves the intestinal microbiome during and after treatment of Clostridium difficile infection (CDI) and reduces both toxin reexpression and recurrence of CDI. "Our view is they are agnostic about this," he said. 14. Simply Wall St. Cookies facilitate the functioning of this site including a member login and personalized experience. Comment: This recommendation places a high value on potential clinical benefits, but implementation is often limited by feasibility considerations. Incentive Awards may not be sold, pledged, assigned, hypothecated, transferred, or disposed of in any manner other than by will or by the laws of descent or distribution and may be exercised, during the lifetime of a Participant, only by the Participant; provided, however that the Committee may permit Options to be sold, pledged, assigned, hypothecated, transferred, or disposed of, on a general or specific basis, subject to such conditions and limitations as the Committee may determine. Amcor Cares was founded as a principal tool in the United States to serve our communities. Capital gain is disregarded . Fidaxomicin versus vancomycin for infection with Clostridium difficile in Europe, Canada, and the USA: a double-blind, non-inferiority, randomised controlled trial. Purpose of the Plan. Panelists also were diverse in gender, geographic distribution, and years of clinical experience. 1. The infusion of bezlotoxumab should be performed while a patient is receiving SOC antibiotics and has been shown to be effective in preventing CDI if administered at any time before ending antibacterial treatment [45]. The quarterly dividend for the period ending 31 March 2023 is 12.25 US cents per share for payment on 20 June 2023. The Committee may require, as a condition to the issuance of Shares pursuant to the terms hereof, that the recipient of such Shares make such covenants, agreements and representations, and that any related certificates representing such Shares bear such legends, as the Committee, in its sole discretion, deems necessary or desirable. Treatment of first recurrence of Clostridium difficile infection: fidaxomicin versus vancomycin. In patients who received vancomycin initially, the guideline suggests the use of tapered-pulse vancomycin or fidaxomicin for recurrences. Resource use (monetary costs and cost-effectiveness, for example) was rated as of limited importance by the panel and was not included in the initial assessment. A history of prior CDI is a prominent risk factor for further recurrences and is addressed separately below. This recommendation remains unchanged. While IDSA and SHEA make every effort to present accurate, complete, and reliable information, these guidelines are presented as is without any warranty, either express or implied. Important safety alert regarding use of fecal microbiota for transplantation and risk of serious adverse reactions due to transmission of multi-drug resistant organisms. No license or permission is granted to any person or entity, and prior written authorization by IDSA is required to sell, distribute, or modify the guidelines, or to make derivative works of or incorporate the guidelines into any product, including but not limited to clinical decision-support software or any other software product. (ii) provide for the termination of an Incentive Award in (whether or not then exercisable or vested) in exchange for an award with respect to (1)some or all of the cash, securities and/or other property, if any, which a holder of the number of Shares subject to such Incentive Award would have received in such transaction upon the exercise of such Incentive Award or realization of the Participants rights as of the date of occurrence of the transaction (and, for the avoidance of doubt, if as of the date of the occurrence of the transaction the Committee determines in good faith that no amount would have been attained upon the exercise of such Incentive Award or realization of the Participants rights, then such Incentive Award may be terminated by the Company without payment) or (2)securities of the acquirer or surviving entity, or any combination of the foregoing and, incident thereto, in any case, make an equitable adjustment as determined by the Committee in the exercise price of the Incentive Award, or the number of securities or amount of property subject to the Incentive Award or provide for a payment (in cash or other property) to the Participant to whom such Incentive Award was granted in partial consideration for the exchange of the Incentive Award. Antimicrobial activities of fidaxomicin. The Chair of the Guidelines panel (S. The Committees granting of an Incentive Award to a Participant at any time shall neither require the Committee to grant an Incentive Award to such Participant or any other Participant or other Person at any time nor preclude the Committee from making subsequent grants to such Participant or any other Participant or other Person. The Company shall pay any amount payable with respect to an Incentive Award in accordance with the terms of such Incentive Award, provided that the Committee may, in its discretion, defer, or give a Participant the election to defer, the payment of amounts payable with respect to an Incentive Award subject to and in accordance with the terms of a Deferred Compensation Plan. PDF Amcor and Bemis combination - assets.ctfassets.net The pooled analysis of these 2 RCTs demonstrates that the addition of bezlotoxumab reduced CDI recurrence after initial clinical cure at 12 weeks (RR: .62; 95% CI: .51.75; moderate certainty evidence) and reduced CDI-associated hospital readmission at 30 days (RR: .46; 95% CI: .29.71; very low certainty evidence), but failed to show a reduction in mortality (RR: .94; 95% CI: .661.34; low certainty evidence). The Committee and, to the extent it so provides, any subcommittee, shall have sole authority to determine whether to review any actions and/or interpretations of any such administrator, and if the Committee, or subcommittee, shall decide to conduct such a review, any such actions and/or interpretations of any such administrator shall be subject to approval, disapproval, or modification by the Committee or subcommittee. 5. (m) Effective Date means the date the Plan is adopted. Because fidaxomicin, like vancomycin, is minimally absorbed and achieves high fecal concentrations, fidaxomicin in a tapered and pulsed regimen following suppressive treatment has been used successfully in patients with multiple CDI recurrences [34]. Clinical practice guidelines for Clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Consequently, the panel judges that patients experiencing recurrent CDI will invariably put a high value on avoidance of a subsequent CDI episode. Get the latest Amcor PLC (AMCR) real-time quote, historical performance, charts, and other financial information to help you make more informed trading and investment decisions. The pooled analysis of the 4 included studies demonstrates that fidaxomicin increased sustained response of CDI 4 weeks after end of therapy as compared with standard vancomycin (risk ratio [RR]: 1.16; 95% confidence interval [CI]: 1.091.24; moderate certainty of evidence), while its use resulted in comparable CDI initial clinical cure (RR: 1.00; 95% CI: .961.04; moderate certainty of evidence) and failed to show a reduction in mortality (RR: .90; 95% CI: .661.23; moderate certainty of evidence). "The low rate of adverse events and lack of infectious complications in this series prompted us to conclude that the presence of active malignancy or recent chemotherapy should not preclude the use of FMT in this high-risk population," explains Sahil Khanna, M.B.B.S. One of these studies, a retrospective multicentered cohort study, evaluated 200 patients receiving bezlotoxumab in addition to SOC antibiotics (vancomycin in 130 patients [68.5%], fidaxomicin in 60 patients [30.0%], and metronidazole in 3 patients [1.5%]) from US outpatient infusion centers from 2017 to 2018 [41]. (d) Board of Directors means the Board of Directors of Amcor. Sheitoyan-Pesant C, Abou Chakra CN, Ppin J, Marcil-Hguy A, Nault V, Valiquette L. Clinical and healthcare burden of multiple recurrences of Clostridium difficile infection. 19. The overall certainty in the evidence was rated as moderate due to the unblinded design of the Guery 2018 study, especially for self-reported outcomes, and to imprecision issues due to small number of events for some outcomes (seeTable 2). Decisions of the Committee shall be final, binding and conclusive on all parties. With the addition of a new RCT comparing fidaxomicin and vancomycin, which also included patients with recurrent CDI [16], evidence now suggests fidaxomicin should be preferred over vancomycin in this setting. Subject to the terms of an Award Agreement, in the event of a Change in Control, (A)Incentive Awards that vest based on time-based criteria will not vest on a Change in Control but will vest if the applicable Participant is terminated without Cause within two years after the consummation of a Change in Control and (B)all performance-based Incentive Awards will convert to time-based Incentive Awards that will be subject to clause (A), with the number of Shares to be determined based on assuming either (1)actual performance to date of a Change in Control (extrapolated as appropriate to the end of the performance period), (2)target performance or (3)the higher of (1)or (2), in the discretion of the Committee. The panels expert experience also suggests that patients with multiple recurrent CDI episodes become increasingly desperate with each subsequent CDI episode and are willing to consider nonstandard or nonapproved therapies. Where applicable, the guideline methodologist pooled the data using a random-effects model (fixed-effects model for pooling of rates) using RevMan 5.4 [9]. In the event that the price of a Share shall not be so reported, the Fair Market Value of a Share shall be determined by the Committee in its sole discretion taking into account the requirements of Section409A of the Code. For example, patients who received metronidazole as a first line treatment should receive vancomycin or fidaxomicin for recurrences. Birch T, Golan Y, Rizzardini G, et al. Cookies are also used to generate analytics to improve this site as well as enable social media functionality. The Cochrane Collaborations tool for assessing risk of bias in randomised trials. 2019. Mikamo H, Tateda K, Yanagihara K, et al. Our update of the literature identified 2 more recently published RCTs [16,17] addressing similar clinical questions (seeFigure 2). Except as otherwise expressly provided in Section8 hereof or in Participants Award Agreement, no adjustment of any Incentive Award shall be made for dividends or other rights for which the record date occurs prior to the date of such issuance. The tax credit amount that can be claimed depends on the amount of foreign tax due and U.S. tax liability. JAMA Clinical Guidelines Synopsis: Diagnosis and treatment of Clostridium difficile infection. The final evidence summaries were presented to the whole panel for deliberation and drafting of recommendations. No grants of Incentive Awards may be made under the Plan after the tenth anniversary of the date upon which the Plan was approved by the Board of Directors. Gerding DN. As a reminder, FMT is recommended only for patients with multiple recurrences of CDI who have failed appropriate antibiotic treatments and where appropriate screening of donor and donor fecal specimens has been performed, in accordance with these newer FDA recommendations [4,5].
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