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Wednesday
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10 August, 2022 |
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Be sure to check out Lei Lei Wu’s expert webinar tomorrow on non-opioid pain drug R&D and the litany of failures — register here. |
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Zachary Brennan |
Senior Editor, Endpoints News
@ZacharyBrennan
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President Joe Biden (AP Images) |
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by Zachary Brennan
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The fact that the new drug price negotiations for certain blockbuster Medicare drugs — due for a partisan thumbs up in the US House of Representatives on Friday and a signature from President Joe Biden soon after — don't take effect until 2026 means there'll be plenty of time for PhRMA and others in biopharma to weigh their legal options. But what PhRMA or any biopharma company may potentially sue over will be the key, as legal experts point to the complicated negotiations side of the reconciliation bill, which beginning in 2026 would kick off these price concessions for 10 of the most expensive single-source drugs in Medicare's Part D program, building up to about 60 drugs from both Part D and B by 2030, with prices generally capped by at least 40%. Considerable attention by Congress has been paid to smaller companies and drugs and biologics with impending competition. For instance, in 2029 and 2030, there would be a maximum fair price floor of 66% of the average non-FAMP for small biotech companies' biologics (compared to 75% for most drugs that have been on the market for less than 12 years), according to the law firm Hogan Lovells. Still, if manufacturers fail or decline to comply with the negotiation process, they would be subject to a significant excise tax (building up from 65% of a drug's sales to 95%), which is a stick so large that it could potentially run afoul of the excessive fines clause of the Eighth Amendment of the Constitution, legal experts said. |
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by Zachary Brennan
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The Pharmaceutical Research and Manufacturers of America — and their fleet of drug industry lobbyists on Capitol Hill — are known for never losing. Whenever a big drug pricing bill comes up, an army of the industry group's lobbyists descend onto the Hill and either smash it outright or dismantle it piece by piece. But for perhaps the largest drug pricing reforms ever enacted, after more than a decade of Congress trying and failing to allow Medicare to negotiate prescription drug prices, those same lobbyists and their biopharma clients were dealt a stunning blow on Sunday afternoon. Senate Democrats salvaged all 50 of their seats (plus Vice President Kamala Harris to break the tie) to hold off Republican amendments after more than a dozen hours of overnight voting to pass a wider-ranging tax and climate bill. The win for the Senate Dems, teeing up another partisan thumbs-up vote in the House this Friday and a guaranteed President Joe Biden signature, means that for the first time ever, the federal government will be able to negotiate and/or set prices on some of the most expensive drugs that, via its Centers for Medicare and Medicaid Services, it pays for. The bill also caps seniors’ out-of-pocket spending for prescription drugs at $2,000 per year — a historic move as some seniors on certain treatments spend upwards of $2,000 per month on their drugs. |
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FDA commissioner Rob Califf (Tom Williams/CQ Roll Call via AP Images) |
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by Zachary Brennan
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The Senate won't return from its summer recess until Sept. 6, but when it does, it officially has 18 business days to finalize the reauthorization of the FDA user fee programs for the next 5 years, or else thousands of drug and biologics reviewers will be laid off and PDUFA dates will vanish in the interim. FDA commissioner Rob Califf recently sent agency staff a memo explaining how, "Our latest estimates are that we have carryover for PDUFA , the user fee funding program that will run out of funding first, to cover only about 5 weeks into the next fiscal year." That means Congress has a tiny cushion of about a month, until Nov. 4, to get its act together. Right now, there are vast differences between the House-passed version of the bill from early June, and the Senate's previously introduced version, which it has yet to vote on. While there are differences between the two versions, on major issues like the regulation of IVDs and cosmetics, both the House and Senate agree that accelerated approval pathway reforms should be added to the user fee deals. But industry and others are making the case for not going too far with those reforms, especially as accelerated approvals have helped many cancer patients access treatments earlier than they otherwise would have. Amgen researchers recently published a paper explaining, "Over the 30-year history of the accelerated approval program, there have been relatively few delinquent cases or dangling approvals. Legislative or other changes to the program should be based on cumulative experience, not outliers." |
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by Nicole DeFeudis
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After making it clear that the US’ current monkeypox vaccine supply is insufficient, the FDA on Tuesday authorized a new route of administration that should increase the number of available doses by five-fold. Regulators cleared Bavarian Nordic’s Jynneos vaccine for intradermal injection in adults older than 18. Unlike subcutaneous injection — the current method by which vaccine is delivered under the skin — an intradermal jab goes directly into the skin. It’s believed that this method requires less vaccine, since the dermis is rich in dendritic cells which specialize in taking up foreign antigens and presenting them to the immune system, according to Daniel Kuritzkes, chief of infectious diseases at Brigham and Women’s Hospital in Boston. “In recent weeks the monkeypox virus has continued to spread at a rate that has made it clear our current vaccine supply will not meet the current demand,” FDA commissioner Robert Califf said in a news release. The news comes as the New York Times reports that about 20 million doses of the vaccine have expired in the US national stockpile. The downside to intradermal injection? It’s more difficult to perform correctly, William Schaffner, a professor in Vanderbilt University’s infectious diseases division, told Endpoints News on Tuesday. As Schaffner put it, intradermal injection is “a bit of an art form.” It was most commonly used for tuberculosis skin tests; however, he noted that it’s likely the average nurse now may have never given an intradermal inoculation, or only had brief exposure. It’s much easier to stick a needle through the skin for a subcutaneous injection. |
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by Kyle LaHucik
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With the rising number of monkeypox cases, leading researchers at the CDC, FDA and NIH are calling on a randomized clinical trial to see if an approved smallpox drug is effective at treating monkeypox. No monkeypox treatments are approved in the US, so patients looking to get relief for their lesions and other symptoms from the virus must go through a set of hurdles to get the smallpox drug through a government expanded access program. Approved for smallpox in 2018, the drug is marketed as TPOXX by the biotech SIGA. The European Union approved it for monkeypox in addition to smallpox earlier this year and the UK followed suit in July. In an opinion piece published in the New England Journal of Medicine on Wednesday, government researchers said the NIH’s National Institute of Allergy and Infectious Diseases is working with the AIDS Clinical Trials Group, which has overseen studies of HIV meds since the 1980s, to set up a clinical trial to test TPOXX for monkeypox. But while NIAID, ACTG and SIGA all confirmed to Endpoints News via email that a US-based clinical trial of the drug is being planned, they declined to say when it would start. Activists argue the trial should have taken place before monkeypox became a global outbreak because the virus has been endemic in some countries in Africa for years. “Adults with monkeypox infection, including people living with HIV, would be eligible to enroll. NIAID will share more information as it becomes available,” the NIAID said in an emailed statement. |
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by Zachary Brennan
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Federal officials said yesterday that shipments of Eli Lilly's bebtelovimab — one of the final two remaining mAb treatments for Covid-19 — would halt later this month, setting up a commercial market where the government no longer pays for the doses and hospitals and other clinics will have to purchase supplies. According to ASPR, the arm of HHS that ships Covid-19 drugs, states have ordered 627,536 bebtelovimab courses, and 383,515 courses have been administered as of July 31. The US has paid Lilly a total of about $1.27 billion for all of the courses so far, amounting to about $2,100 per course to start and then receiving a discounted $1,833 ASP for the later part of the deal. According to the Wall Street Journal, Lilly’s list price for bebtelovimab is $2,100 per dose. “I don’t anticipate that this will in any way stimulate usage of the product,” Dan Skovronsky, Lilly’s chief scientific and medical officer, told WSJ in an interview. “It’s more just about, how do we keep it available despite the U.S. government not being able to purchase it anymore. That’s why we’re switching to a different model here.” On Friday, the FDA updated the bebtelovimab Letter of Authorization to remove the requirement that distribution will be controlled by the US government. Lilly said it will make bebtelovimab commercially available for purchase by US states/territories, hospitals and a broad set of other providers like infusion centers, long-term care facilities, and clinics through AmerisourceBergen Specialty Distribution, the sole distributor beginning the week of Aug. 15. |
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by Zachary Brennan
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The FDA said Tuesday that it recently became aware of a nitrosamine impurity, Nitroso-STG-19 or NTTP, in certain samples of Merck's type 2 diabetes drug Januvia. To avoid a shortage of the drug that pulled in more than $10.5 billion for Merck in 2020 and 2021, and to help ensure patients have access to an adequate supply, the FDA said it will not object to the temporary distribution of sitagliptin containing the impurity above the acceptable intake limit. Typically, if a drug contains levels of nitrosamines above the acceptable daily intake limit, the FDA recommends the manufacturer conduct a recall. "Sitagliptin is a prescription drug used to control high blood sugar in patients with type 2 diabetes mellitus. It could be dangerous for patients with this condition to stop taking their sitagliptin without first talking to their health care professional. FDA recommends prescribers continue to use sitagliptin when clinically appropriate to prevent a gap in patient treatment," the agency said. The FDA also said it will determine on a case-by-case basis whether drugs should be released for distribution. NTTP belongs to a class of potentially cancer-causing nitrosamine compounds, detected via laboratory tests. "Although there are no data available to directly evaluate the carcinogenic potential of NTTP, FDA used information available on closely related nitrosamine compounds to calculate lifetime exposure limits for NTTP," the agency said. "Agency scientists evaluated the risk of exposure to NTTP at interim acceptable intake levels up to 246.7 ng per day and determined that it presents minimal additional cancer risk when compared to a lifetime of exposure to NTTP at the 37 ng per day level." |
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by Zachary Brennan
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Back in 2018, Swiss drugmaker Ferring Pharmaceuticals made a big bet on Minnesota-based Rebiotix, buying up the company for its experimental poop-based drug implant to treat an infection caused by C. difficile, a potentially dangerous bacteria, in a new way. Four years later, Ferring's fecal microbiota transplant, dubbed RBX2660 or Rebyota, will face the FDA's adcomm of outside vaccine experts on Sept. 22, debating whether the agency should license the transplant as a treatment for adults following antibiotic treatment for recurrent C. difficile infection. Back in May, Ferring announced that a Phase III, placebo-controlled trial with about 600 participants showed that RBX2660 demonstrated superior efficacy versus placebo (70.4% and 58.1%, respectively) at eight weeks post-treatment, with a comparable safety profile to placebo. Already granted fast track, orphan, and breakthrough therapy designations from the FDA, RBX2660's pivotal Phase III results build on nearly a decade of research on the microbiome data collected over six controlled clinical trials with more than 1,000 participants, Rebiotix said in a statement. But prior to that Phase III announcement, the FDA in June 2019 (updated in March 2020) raised concerns of the potential risk of serious or life-threatening infections with the use of fecal microbiota for transplantation. Two immunocompromised adults who received investigational FMT developed invasive infections caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (E. coli), and one of the individuals died, the FDA said. But Ferring said in a statement that it doesn't have any details on the patients mentioned in the FDA's safety alert, as they were not enrolled in the company's clinical trials. |
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by Tyler Patchen
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Several pharma groups are laying out the positives and negatives of new FDA draft guidance on how best to handle drug shortages. The draft is intended to help companies develop and implement risk management plans (RMPs) to assist with any shortages of drugs or biologics. The guidance recommends a framework and factors for stakeholders to develop RMPs for their establishments, API manufacturers and others. Civica, a government-funded nonprofit aiming to reduce chronic drug shortages, commented alongside the Mayo Clinic and Sanford Health — all generally supporting RMPs. However, they say there is an opportunity to prevent or mitigate shortages by improving upon inventory management once supply disruption is identified. “Currently, health systems generally learn about a drug shortage once the product becomes unavailable, which may be weeks or months after the manufacturer supply disruption has become known to the FDA. If health systems know about shortages sooner, it may be able to adjust utilization, such as by using the drug only when necessary or switching to alternative products for suitable patients, for example, using an oral medication instead of an injectable,” the comment said. The health systems can implement waste reduction strategies or repackage the contents of vials to allow for use to treat multiple patients if a shortage were to occur, they obeserve. But for them to be effective, early detection is key. The comment recommends that drug distributors have a plan in place immediately to put a drug on allocation when notified by the FDA of a potential impending shortage. |
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Joe Todisco, CorMedix CEO |
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by Tyler Patchen
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Following a C-suite shuffle, a shuttering of its European operations and a CRL for its treatment to prevent bloodstream infections in patients undergoing chronic hemodialysis, CorMedix is still not impressing the FDA. The biotech has now been given a second rejection letter, as the NDA surrounding its antifungal solution, DefenCath, cannot be approved until issues surrounding its contract manufacturing organization and the supplier of the API heparin during inspections are resolved, CorMedix said Monday afternoon. While CorMedix has been working with its third-party manufacturer to correct any problems, it has still not been cleared to go ahead with the NDA. Separately, the FDA also inspected the facility of the company’s heparin supplier. This led to a warning letter for the API supplier for having manufacturing deficiencies for a non-heparin API. Though the supplier has retained an independent consultant to correct the problems, they could not be resolved before the PDUFA date. As a result of these issues, CorMedix has now sought another CMO in Alcami Corporation and is in the process of having its tech transferred over. CorMedix is also getting its supply of heparin from another alternative source as well. CorMedix now expects to send its NDA back around the first quarter of next year. “While I am disappointed that we will not receive FDA approval for the NDA on our PDUFA date, I am encouraged to have substantive labeling and clinical review completed by FDA and I am confident there is a line of sight to FDA approval of the NDA, once either our existing CMO and API supplier obtain compliance clearance, or we are able to submit and obtain regulatory approval for manufacturing at Alcami,” said CorMedix CEO Joe Todisco in a statement. |
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Warren Huff, Reata Pharmaceuticals CEO |
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by Lei Lei Wu
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In its Q2 report Monday, Reata Pharmaceuticals said that the FDA continues to have concerns about its Friedreich’s ataxia drug. On Tuesday, those concerns manifested in a three-month delay on an FDA approval decision. Reata’s new FDA decision deadline for its Friedreich’s ataxia drug, omaveloxolone, is the end of February 2023, it announced this morning. In the Q2 report, Reata noted that the FDA was concerned about the efficacy of omaveloxolone. The Plano, TX-based biotech said that in response to those concerns, it submitted additional data from its clinical trial. But in order to review that new data, the FDA needs more time, hence the three-month delay, Reata said Tuesday morning. Friedreich’s ataxia is a rare genetic disease in which nerve fibers degenerate over time. In 2019, Reata surprised analysts with a positive readout on its pivotal omaveloxolone trial. However, that initial buzz died a year later when the FDA said the supplemental data Reata submitted on its pivotal trial was not enough, requesting that the biotech run an additional trial. Reata’s stock RETA dropped around 30% Monday morning in reaction to the news of another delay on the drug. While there is currently no approved treatment for Friedreich’s ataxia, the few biotechs that have gone after the indication haven’t seen much success. In 2016, Horizon’s $50k/month drug Actimmune, already approved for two other indications, flunked a Phase III trial for Friedreich’s ataxia. And Larimar Therapeutics’ Phase I program has been on clinical hold after non-human primates died in preclinical testing. |
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