Latest news with #PFS
Cision Canada
13 hours ago
- Business
- Cision Canada
Graphite One's Graphite Creek Project Approved for FAST-41 Federal Permitting Dashboard
Graphite One becomes the first Alaskan Critical Mineral mining project on the FAST-41 Dashboard FAST-41 status follows completion of Graphite One Feasibility Study funded by a $37.3M award under the Defense Production Act G1 enters Permitting Phase as Presidential Critical Mineral Executive Order calls for "Immediate Measures to Increase American Mineral Production" and "Unleashing Alaska's Extraordinary Resource Potential" VANCOUVER, BC, June 3, 2025 /CNW/ - Graphite One Inc. (TSXV: GPH) (OTCQX: GPHOF) (" Graphite One", the " Company", or "G1"), is pleased to announce that the Company's Graphite Creek project – the upstream anchor for G1's complete U.S.-based advanced graphite supply chain (" Graphite Creek")– has been accepted as a "covered project" onto the FAST-41 Permitting Dashboard. Graphite One's project is the first Alaskan mining project to be listed on the FAST-41 Dashboard. "The approval of Graphite Creek as FAST-41's first Alaskan mining project is a major step for G1 and our complete U.S.-based supply chain strategy," said Anthony Huston, CEO of Graphite One. "With President Trump's Critical Mineral and Alaska Executive Orders, Graphite One is positioned at the leading edge of a domestic Critical Mineral renaissance that will power transformational applications from energy and transportation to AI infrastructure and national defense." Graphite One's domestic supply chain is planned to produce graphite concentrate from the Graphite Creek deposit North of Nome, Alaska and Anode Active Material at a facility to be constructed in Warren, Ohio, subject to financing (the " Project"). FAST-41 status follows publication of Graphite One's Feasibility Study (" FS") on April 23, 2025, which, with the support of the Department of Defense Production Act (DPA) award, was completed 15 months ahead of schedule. The annual graphite concentrate capacity of the Graphite Creek Mine in the FS was increased from that in the 2022 Pre-Feasibility Study (" PFS") – from 53,000 tpy to 175,000 tpy while maintaining a 20-year mine life. Measured plus Indicated Resources increased to 322% of the PFS resource. The FS projects a post-tax internal rate of return of 27%, using an 8% discount rate, with a net present value of $5.03 billion and a payback period of 7.5 years. FAST-41 streamlines the permitting process by providing improved timeliness and predictability by establishing publicly posted timelines and procedures for federal agencies, reducing unpredictability in the permitting process. FAST-41 also provides issue resolution mechanisms, while the federal permitting dashboard allows all project stakeholders and the general public to track a project's progress, including periods for public comment. The action drew strong support from Alaska's leading public officials: "America's dependency on foreign minerals and metals is a drag on our economy and a danger to our national security," said Alaska Governor Mike Dunleavy. "As the largest natural graphite deposit in the nation, adding Graphite Creek to the FAST-41 Permitting Dashboard sends a strong signal that Alaska is key to U.S. Critical Mineral development." "Graphite One's addition to the FAST-41 permitting dashboard is yet another indication that this project is a national priority of strategic importance," said Senator Lisa Murkowski. "There is no question that developing the largest natural graphite deposit in all of North America is far better for our economy, security, and competitiveness than importing the entirety of our supply from unstable nations like Mozambique. I thank the Trump administration for adding Graphite One to the dashboard and look forward to the day this project comes online." "I want to congratulate Graphite One, which has achieved this milestone thanks to funding from the Defense Production Act, something I have been working on relentlessly in the Senate since the project's inception," said Senator Dan Sullivan. "This project has the potential to open up our state's abundant reserves of critical minerals and metals, which would also be very significant for our country's national security. We must end America's dependence on China for critical minerals, like graphite, resources that are necessary for alternative energy and sources and critical defense technologies. Thankfully, President Trump understands our state's great potential, and is determined to help unleash our vast resources and create good paying jobs to Alaskans. Graphite One's FAST-41 status is great news for our state and our country." "Securing our supply chains for critical minerals is a core priority and requires a whole of government approach." said Alaska Congressman Nick Begich. "Our national security, sovereignty, and continued self-determination require that we take action, and Graphite One is leading the way." Graphite One's Complete U.S.-Based Supply Chain Strategy The Project is planned as an integrated business operation to produce lithium-ion battery anode materials and other graphite products for the U.S domestic market on a commercial scale using primarily natural graphite from Alaska. The Project combines the operation of an advanced graphite manufacturing facility to be located in Warren Ohio with the supply of natural flake graphite from the Company's proposed Graphite Creek Mine in Alaska. The resources associated with the Company's Alaska State mining claims were cited by the U.S. Geological Survey in January 2022 as America's largest natural graphite deposit 1, and in 2023, "as among the largest in the world." This precedes the FS-verified deposit amount increase. The Ohio manufacturing facility received a $325M Letter of Interest from the EXIM Bank in September 2024. About the Permitting Council and FAST-41 Established in 2015 by Title 41 of the Fixing America's Surface Transportation Act (FAST-41), the Permitting Council is a federal agency charged with improving the transparency and predictability of the federal environmental review and authorization process for certain critical infrastructure projects. The Permitting Council is comprised of the Permitting Council Executive Director, who serves as the Council Chair; 13 federal agency Council members (including deputy secretary-level designees of the Secretaries of Agriculture, Army, Commerce, Interior, Energy, Transportation, Defense, Homeland Security, and Housing and Urban Development, the Administrator of the Environmental Protection Agency, and the Chairs of the Federal Energy Regulatory Commission, Nuclear Regulatory Commission, and the Advisory Council on Historic Preservation); and the Chair of the White House Council on Environmental Quality and the Director of the Office of Management and Budget. The Permitting Council coordinates federal environmental reviews and authorizations for projects that seek and qualify for FAST-41 coverage. FAST-41 covered projects are entitled to comprehensive permitting timetables and transparent, collaborative management of those timetables on the Federal Permitting Dashboard. FAST-41 covered projects may be in the energy production, electricity transmission, energy storage, surface transportation, aviation, ports and waterways, water resource, broadband, pipelines, manufacturing, mining, carbon capture, semiconductors, artificial intelligence and machine learning, high-performance computing and advanced computer hardware and software, quantum information science and technology, data storage and data management, and cybersecurity sectors. The Permitting Council also serves as a federal center for permitting excellence, supporting federal efforts to improve infrastructure permitting including and beyond FAST-41 covered projects to the extent authorized by law, including activities that promote or provide for the efficient, timely, and predictable completion of environmental reviews and authorizations for federally-authorized infrastructure projects. Qualified Person Jason Todd, with Barr Engineering Co. is the primary qualified person for the Feasibility Study incorporated in the NI 43-101 technical report that is available under the Company's SEDAR+ profile at and the Company's website. Mr. Todd is a Qualified Person as defined under 43-101 and has reviewed and approved the technical content of this release. About Graphite One Inc. GRAPHITE ONE INC. (TSX‐V: GPH; OTCQX: GPHOF) continues to develop its Graphite One Project (the " Project"), with the goal of becoming an American producer of high grade anode materials that is integrated with a domestic graphite resource. The Project is proposed as a vertically integrated enterprise to mine, process and manufacture high grade anode materials primarily for the lithium‐ion electric vehicle battery market. On Behalf of the Board of Directors "Anthony Huston" (signed) For more information on Graphite One Inc., please visit the Company's website, On X @GraphiteOne Neither the TSX Venture Exchange nor its Regulation Services Provider (as that term is defined in the policies of the TSX Venture Exchange) accepts responsibility for the adequacy or accuracy of this release. Cautionary Note Regarding Forward-Looking Statements All statements in this release, other than statements of historical facts, including those related to the Fast 41 listing and the anticipated impact of the FAST-41 status, any statements related to the planned production of any mineral reserves and resources, the construction of the Warren, Ohio facility, and events or developments that the Company intends, expects, plans, or proposes are forward-looking statements. Generally, forward ‐ looking information can be identified by the use of forward ‐ looking terminology such as "proposes", "expects", "is expected", "scheduled", "estimates", "projects", "plans", "is planning", "intends", "assumes", "believes", "indicates", "to be" or variations of such words and phrases that state that certain actions, events or results "may", "could", "would", "might" or "will be taken", "occur" or "be achieved". The Company cautions that there is no certainty that the Fast 41 listing will impact the Company as set forth in this press release, that the Graphite Creek Project produces the minerals set out in the FS or that the facility will be built in Warren, Ohio. Although the Company believes the expectations expressed in such forward-looking statements are based on reasonable assumptions, such statements are not guarantees of future performance and actual results or developments may differ materially from those in the forward-looking statements. Factors that could cause actual results to differ materially from those in forward-looking statements include market prices, exploitation and exploration successes, continuity of mineralization, uncertainties related to the ability to obtain necessary permits, licenses and title and delays due to third party opposition, changes in government policies regarding mining and natural resource exploration and exploitation, and continued availability of capital and financing, and general economic, market or business conditions. Readers are cautioned not to place undue reliance on this forward-looking information, which is given as of the date it is expressed in this press release, and the Company undertakes no obligation to update publicly or revise any forward-looking information, except as required by applicable securities laws. For more information on the Company, investors should review the Company's continuous disclosure filings that are available at
Yahoo
13 hours ago
- Business
- Yahoo
Probe Awards Key Engineering Contracts to Advance Novador Project Pre-Feasibility Study
Highlights: Ausenco Engineering Canada ULC will lead the Pre-Feasibility Study (PFS) and will be responsible for the process plant design, the supporting infrastructure, overall opex and capex. G Mining Services will lead the mining engineering scope of the project including mining opex and capex. GHD will lead the scope of the project related to the design of tailings and water management infrastructures. Probe has successfully completed a 50,000-metre infill drilling program to support the PFS, which remains on track for completion by year-end 2025. TORONTO, June 03, 2025 (GLOBE NEWSWIRE) -- PROBE GOLD INC. (TSX: PRB) (OTCQB: PROBF) ("Probe" or the "Company") is pleased to announce that it has awarded all major engineering contracts for project management services related to the Pre-Feasibility Study ('PFS') of its flagship Novador Project. The PFS is scheduled for completion by the end of 2025. Ausenco Engineering Canada ULC ('Ausenco') has been appointed to lead the PFS and will oversee project timelines, milestones, and deliverables. Ausenco will contribute technical expertise across core engineering disciplines, including infrastructure, metallurgy, and processing and will produce a project execution plan with related capex and opex to advance the project towards the future Feasibility Study and permitting. G Mining Services Inc. (GMS) has been engaged to lead all mining engineering aspects of the PFS. GMS' scope includes the open pit and underground mining engineering and design, mine planning, mining infrastructure, mining opex and capex, and the development of the mining execution strategy. GHD has been appointed for all engineering aspects related to tailings and water management infrastructures. GHD is currently producing the physical environment baseline studies, and they will be able to leverage their understanding of the Novador project site and the permitting requirements into their design and the selection of optimum solutions. David Palmer, President and CEO of Probe Gold, states 'With these key contracts in place, Probe is well positioned to advance the Novador Project into its next phase of development and deliver a robust, high-quality Pre-Feasibility Study. By working with global leaders, Ausenco for process infrastructure, G Mining Services for mining engineering, and GHD for water and tailings management, we have strong confidence in the technical quality and scope of the work ahead. These collaborations support our timeline to deliver the PFS by year-end. We see significant potential to enhance the current study and look forward to drawing on the expertise of our consultants throughout the process. At the same time, we are making steady progress on our permitting strategy. With the successful completion of our recent financing, Probe is fully funded to advance through the next stages of regulatory and permitting work, creating meaningful value for our shareholders.' About Probe's Novador Project Since 2016, Probe Gold has been consolidating its land position in the highly prospective Val d'Or East area in the province of Quebec with a district-scale land package of 835 square kilometres that represents one of the largest land holdings in the Val-d'Or mining camp. The Novador project represents one property block of 202 square kilometres that hosts four past producing mines (Beliveau Mine, Bussiere Mine, Monique Mine and Beaufor Mine) and contains 80% of the Company's gold resources in Val-d'Or East. Novador is situated in a politically stable and low-cost mining environment that hosts numerous active producers and mills. About AusencoAusenco is a global company delivering innovative, value-add consulting, studies, project delivery, asset operations and maintenance solutions to the minerals and metals and industrial sectors. Ausenco operates from 21 offices across five continents, delivering services worldwide with a strong track record of successfully completing projects in Quebec. Study work in Quebec includes Agnico Eagle Mines' Wasamac FS and FS Update, O3 Mining's Marban PFS and Probe Gold's Novador PEA and PEA Update. Other notable PFS studies completed in Canada include NexGold's Goliath Project and St. Barbara's 15-Mile Project and the recently awarded Mayfair Gold Fenn-Gib Project. Beyond Quebec, Ausenco has also recently executed major projects such as Alamos Gold's Magino Project in Ontario, St. Barbara's Moose River Project in Nova Scotia and SilverCrest Metals' Las Chispas Project in Mexico. ( About G MiningG Mining Services is an entrepreneurial minded and multidisciplinary company which provides professional services to both underground and open pit mining projects in precious, base or industrial metals. G Mining has the expertise to develop a resource through all stages from exploration and development to construction, commissioning, and full-scale operations. ( About GHDGHD is a global, employee-owned professional services company founded in 1928 and headquartered in Australia. Operating across five continents, GHD brings together more than 1,800 professionals in Canada. We collaborate with mining clients across the globe to deliver integrated solutions that address complex environmental and engineering challenges. In Canada, we are currently supporting multiple mine waste and water management Pre-Feasibility Studies across Nova Scotia, New Brunswick, British Columbia, and Quebec. These engagements span key commodities including gold, base metals, and lithium. By bringing together expertise in engineering, environmental science, architecture, and construction, we help our clients plan and deliver sustainable outcomes that create long-term value. ( About Probe GoldProbe Gold Inc. is a leading Canadian company focused on the acquisition, exploration, and development of highly prospective gold properties. The Company is well-funded and dedicated to exploring and developing high-quality gold projects. Notably, it owns 100% of its flagship asset, the multimillion-ounce Novador Gold Project in Québec, as well as an early-stage Detour Gold Québec project. Probe controls a large land package of approximately 1,835-square-kilometres of exploration ground within some of the most prolific gold belts in Québec. The Company's recent Novador updated Preliminary Economic Assessment outlines a robust mining plan with an average annual gold production of 255,000 ounces over a 12.6-year mine life. Val-d'Or properties include gold resources totaling 6,728,600 ounces in the Measured and Indicated category and 3,277,100 ounces in the Inferred category along all trends and deposits. On behalf of Probe Gold Inc., President & Chief Executive OfficerPlease visit our website at or contact: Seema SindwaniVice-President of Investor Relationsinfo@ Forward-Looking Statements Neither TSX nor its Regulation Services Provider (as that term is defined in the policies of the TSX) accepts responsibility for the adequacy or accuracy of this release. This news release includes certain "forward-looking statements" which are not comprised of historical facts. Forward-looking statements include estimates and statements that describe the Company's future plans, objectives or goals, including words to the effect that the Company or management expects a stated condition or result to occur. Forward-looking statements may be identified by such terms as 'believes', 'anticipates', 'expects', 'estimates', 'may', 'could', 'would', 'will', or 'plan'. Since forward-looking statements are based on assumptions and address future events and conditions, by their very nature they involve inherent risks and uncertainties. Although these statements are based on information currently available to the Company, the Company provides no assurance that actual results will meet management's expectations. Risks, uncertainties, and other factors involved with forward-looking information could cause actual events, results, performance, prospects, and opportunities to differ materially from those expressed or implied by such forward-looking information. Forward looking information in this news release includes, but is not limited to, the Company's objectives, goals or future plans, statements, exploration results, potential mineralization, the estimation of mineral resources, exploration and mine development plans, timing of the commencement of operations and estimates of market conditions, expectations about the use of proceeds from the Offering and final acceptance from the TSX. Factors that could cause actual results to differ materially from such forward-looking information include, but are not limited to the inability of the Company to apply the use of proceeds from the Offering as anticipated, the failure to identify mineral resources, failure to convert estimated mineral resources to reserves, the inability to complete a feasibility study which recommends a production decision, the preliminary nature of metallurgical test results, delays in obtaining or failures to obtain required governmental, environmental or other project approvals, political risks, inability to fulfill the duty to accommodate First Nations and other indigenous peoples, uncertainties relating to the availability and costs of financing needed in the future, changes in equity markets, inflation, changes in exchange rates, fluctuations in commodity prices, delays in the development of projects, capital and operating costs varying significantly from estimates and the other risks involved in the mineral exploration and development industry, an inability to predict and counteract the effects pandemics or other global events on the business of the Company, including but not limited to the effects of the same on the price of commodities, capital market conditions, restriction on labour and international travel and supply chains, and those risks set out in the Company's public documents filed on SEDAR+. Although the Company believes that the assumptions and factors used in preparing the forward-looking information in this news release are reasonable, undue reliance should not be placed on such information, which only applies as of the date of this news release, and no assurance can be given that such events will occur in the disclosed time frames or at all. The Company disclaims any intention or obligation to update or revise any forward-looking information, whether as a result of new information, future events or otherwise, other than as required by in retrieving data Sign in to access your portfolio Error in retrieving data Error in retrieving data Error in retrieving data Error in retrieving data
Yahoo
18 hours ago
- Health
- Yahoo
A popular hair loss drug destroyed my ex-husband's sex drive — and ended our marriage
A bestselling author has shared a heartbreaking story about how a popular hair loss drug led to the demise of her ex-husband's sexual function — and their marriage. Speaking recently on the podcast 'Moral Medicine,' Thammika Songkaeo said she noticed they had no love life to speak of while they were still dating. Her then-boyfriend told her that it was because he had taken Propecia — the brand name of finasteride, which is commonly used to treat hair loss in men. One of the potential side effects is sexual dysfunction. At the time, she thought it was just a temporary issue — or that it would only be a problem intermittently. 'I did not at all realize that it was permanent, serious [and] devastating,' she said. They got married and stayed together for seven years, with Songkaeo convincing her ex to take an erectile dysfunction drug to improve intimacy. The couple welcomed a daughter, but Songkaeo's loneliness worsened. Ultimately, she decided to walk away from the sex-starved marriage. Noting that her ex was a wonderful partner outside of the bedroom, they remained great friends — and Songkaeo went on to write a novel about her experience, 'Stamford Hospital,' which became a No. 1 bestseller on Amazon Singapore. Now, she's trying to spread the word not only about how post-finasteride syndrome (PFS) — a condition in which someone experiences severe side effects after they stop using finasteride — affects its victims, but also the ones they love. 'The depth of the loneliness I felt was to the point where I, myself, was becoming suicidal or having suicidal thoughts,' Songkaeo said. 'I had to call the suicide hotline because it became that bad for me — and, usually, I'm a pretty happy person.' She questions the ethics of distributing a drug that can have such potentially devastating consequences. 'Finasteride has the capacity to dissolve one person so much that it becomes this domino effect…there's just so much destruction around it — and it feels like unnecessary destruction,' she said. Songkaeo was interviewed by podcast host Mark Millich, who made headlines earlier this year by telling the Wall Street Journal that he experienced debilitating side effects after buying finasteride. Some of his side effects included anxiety, dizziness and slurred speech. His sex drive also plummeted, and his genitals shrank and changed shape. Millich previously interviewed a 28-year-old man who reported a roller coaster of side effects due to PFS, including sexual dysfunction, insomnia, severe weight and muscle loss, skin rashes and pelvic pain. 'Every month, I feel like there's a new side effect,' the man said. 'It's really changed my life completely.' In April, the US Food and Drug Administration issued a warning about topical finasteride products distributed by telehealth companies, citing several reports of adverse events such as erectile dysfunction, anxiety, suicidal ideation, brain fog, depression, fatigue, insomnia, decreased libido and testicular pain. If you are struggling with suicidal thoughts or are experiencing a mental health crisis and live in New York City, you can call 1-888-NYC-WELL for free and confidential crisis counseling. If you live outside the five boroughs, you can dial the 24/7 National Suicide Prevention hotline at 988 or go to
New York Post
a day ago
- Health
- New York Post
A popular hair loss drug destroyed my ex-husband's sex drive — and ended our marriage
A bestselling author has shared a heartbreaking story about how a popular hair loss drug led to the demise of her ex-husband's sexual function — and their marriage. Speaking recently on the podcast 'Moral Medicine,' Thammika Songkaeo said she noticed they had no love life to speak of while they were still dating. Her then-boyfriend told her that it was because he had taken Propecia — the brand name of finasteride, which is commonly used to treat hair loss in men. One of the potential side effects is sexual dysfunction. 3 Speaking recently on the podcast 'Moral Medicine,' Thammika Songkaeo shared how post-finasteride syndrome (PFS) led to the demise of her marriage. Moral Medicine/YouTube At the time, she thought it was just a temporary issue — or that it would only be a problem intermittently. 'I did not at all realize that it was permanent, serious [and] devastating,' she said. They got married and stayed together for seven years, with Songkaeo convincing her ex to take an erectile dysfunction drug to improve intimacy. The couple welcomed a daughter, but Songkaeo's loneliness worsened. Ultimately, she decided to walk away from the sex-starved marriage. Noting that her ex was a wonderful partner outside of the bedroom, they remained great friends — and Songkaeo went on to write a novel about her experience, 'Stamford Hospital,' which became a No. 1 bestseller on Amazon Singapore. 3 'The depth of the loneliness I felt was to the point where I myself was becoming suicidal or having suicidal thoughts,' Songkaeo said. Gorodenkoff – Now, she's trying to spread the word not only about how post-finasteride syndrome (PFS) — a condition in which someone experiences severe side effects after they stop using finasteride — affects its victims, but also the ones they love. 'The depth of the loneliness I felt was to the point where I, myself, was becoming suicidal or having suicidal thoughts,' Songkaeo said. 'I had to call the suicide hotline because it became that bad for me — and, usually, I'm a pretty happy person.' She questions the ethics of distributing a drug that can have such potentially devastating consequences. 'Finasteride has the capacity to dissolve one person so much that it becomes this domino effect…there's just so much destruction around it — and it feels like unnecessary destruction,' she said. Songkaeo was interviewed by podcast host Mark Millich, who made headlines earlier this year by telling the Wall Street Journal that he experienced debilitating side effects after buying finasteride. 3 Mark Millich — the host of the podcast — made headlines earlier this year by telling the Wall Street Journal that he experienced debilitating side effects after buying finasteride. X/@Unstoppable218 Some of his side effects included anxiety, dizziness and slurred speech. His sex drive also plummeted, and his genitals shrank and changed shape. Millich previously interviewed a 28-year-old man who reported a roller coaster of side effects due to PFS, including sexual dysfunction, insomnia, severe weight and muscle loss, skin rashes and pelvic pain. 'Every month, I feel like there's a new side effect,' the man said. 'It's really changed my life completely.' In April, the US Food and Drug Administration issued a warning about topical finasteride products distributed by telehealth companies, citing several reports of adverse events such as erectile dysfunction, anxiety, suicidal ideation, brain fog, depression, fatigue, insomnia, decreased libido and testicular pain. If you are struggling with suicidal thoughts or are experiencing a mental health crisis and live in New York City, you can call 1-888-NYC-WELL for free and confidential crisis counseling. If you live outside the five boroughs, you can dial the 24/7 National Suicide Prevention hotline at 988 or go to
Medscape
a day ago
- Health
- Medscape
Skills Lab: Rethinking Surrogate Endpoints Approval
This transcript has been edited for clarity. Hello, everyone. This is Dr Bishal Gyawali, from Queens University, Kingston, Canada. Thank you for joining us in our Skills Lab video series. In the last lecture we discussed how progression-free survival (PFS) response rate and the surrogate endpoints are defined. We talked about the particularities with response rate and PFS, and in the adjuvant setting, with disease-free survival. Today we'll talk about surrogate endpoints and their role in regulatory approval. One question that people commonly ask is: What strength of surrogacy is required for drug approval? Are different strengths of surrogacy required for accelerated approval (or 'conditional' approval) vs regular approval (or 'full' approval)? We would expect that regular approval requires a higher bar of evidence as compared to accelerated approval. Unfortunately, there are no such published criteria, but based on the data we have seen, I think there are probably no unpublished criteria either. If we compare the response rates of drugs that have received accelerated approval vs regular approval, then we don't see much of a difference. Also, in one of these studies from 2002 to 2021, we saw that 30% of approvals were based on response rates from single-arm trials that received regular approval rather than next approval. You would believe that a response rate–based approval would usually be acceleratedor conditional approval so that the drug confirms clinical benefit in the future, but we found that in 30% of these cases, they received upfront, regular, full approval rather than accelerated approval. I call this upfront, premature, regular approval. If you look at the trends of the FDA approval, you'll notice in recent years that the number of approvals based onsurrogate endpoints is increasing, while simultaneously, the number of accelerated approvals is decreasing. At first, it does not make sense because accelerated approvals are supposed to be surrogate-based approvals. What this means is that nowadays we are approving more and more drugs on the basis of surrogate endpoints by giving them full or regular approval rather than accelerated approval, which I think is very concerning from a societal point of view. If we are giving upfront, regular approval, then we can never be sure that they confirm clinical benefit because they don't have a mandate to do such a confirmatory trial. Also, even if these drugs were to fail in subsequent trials, we can't withdraw them. Only accelerated approvals get withdrawn. I'll give you one example:the BOLERO-2 trial of everolimus in breast cancer. As you can see, the first graph is PFS, and there was a 6-month improvement in PFS, with a hazard ratio of 0.36, which led to the drug's approval. It was not accelerated approval; it was full approval. In just 2 years, the overall survival results were published. As you can see in the second graph, the overall survival was negative. Overall survival did not improve, but because it was a full approval, the drug was not withdrawn. I call this premature approval, and we should be asking why we are granting full approval based on surrogate data. One more example: Margetuximab in breast cancer was approved on the basis of PFS improvement. You can see how much PFS improvement there was. It was 5.8 vs 4.9 months, so it was just 0.9 months, or less than 1 month, of PFS improvement. This drug was given full approval, not accelerated approval like it was supposed to. You can look at the date. This drug was approved in December 2020, and just 9 months later, in September 2021, we received overall survival results from this trial. The drug failed to improve overall survival. If we had not given regular approval, then we would have withdrawn this drug, but because it was given premature full approval, the drug was not withdrawn. It took only 9 months to get overall survival data, so why did we not give accelerated approval? That is something we should be asking. We recently published a paper in JCO about why PFS should not be used as a primary endpoint for registration of anticancer drugs. We list several reasons why PFS fails to capture clinical benefit in these trials. I think we should at least agree that, if we're approving drugs based on surrogate endpoints, it should be accelerated or conditional approval and not full approval. The other common question is: If PFS did not lead to overall survival improvement, did it not improve quality of life? We tried to answer that question. First, of course, there is no reason for PFS to correlate with overall survival. As we discussed in the last lecture, nothing magical happens at 20% and not all progression events are the same. Some progression events are more symptomatic than others, therefore the quality-of-life effectis not always predictable. Quality-of-life impact is not only a function of how big the tumor is but also a function of drug toxicities. In recent years, we have seen that PFS has become the default primary endpoint. In the past decade or so, the frequency of trials using PFS at the primary endpoint has increased substantially and now exceeds the percentage of trials with overall survival as the primary endpoint. The strange thing about PFS is that we talk about correlation of PFS with overall survival and how we need to do correlation analysis to confirm that this is a valid surrogate as we saw with the case of bevacizumab in breast cancer, even after eight clinical trials were conducted, was PFS a good surrogate for overall survival in this setting? The answer was that we do not know. Maybe, maybe not. What I'm trying to say here is that, even after eight clinical trials of the same drug in the same setting, we are still unable to conclude definitively whether PFS is a goodsurrogate for overall survival. This means that it is far more expedient to just measure overall survival than to continue to do multiple trials and continue to guess whether PFS is a good surrogate for overall survival. Thank you very much. I'll see you in the next lecture, in which we will talk about physicians' and patients' understanding related to surrogate endpoints.
