Eye Infections, Bacterial

According to the letter from House Republicans, the FDA ended its surprise foreign inspection program in a bid to engender deeper collaboration with India. Once again, U.S. lawmakers are pressing the Food and Drug Administration for clarity around the agency’s tracking of scarce medicines and foreign inspection priorities. After contacting the FDA back in July, Republicans on the House Committee on Energy and Commerce are digging into a Bloomberg report stating that the agency has put the kibosh on its unannounced foreign inspection program.  Drug shortages have become increasingly common and drawn-out affairs in the U.S. in recent years, with medications such as amoxicillin, penicillin, Adderall and certain chemotherapies being some of the most recent and high-profile products to run scarce. Throughout 2023, the issue has garnered concern from U.S. officials and lawmakers on both sides of the aisle. Those shortages can be blamed, at least in part, on the FDA’s wind-down of inspectional activities overseas, a trio of Energy and Commerce Committee Republicans alleged in a letter this week. “The U.S. cannot afford additional disruptions to the drug supply chain that reduce the availability of essential medications and force doctors and patients to make difficult treatment decisions,” the Republican lawmakers wrote to FDA Commissioner Robert Califf, M.D. In their letter, the lawmakers cited a 2022 study that showed FDA foreign inspections were down 79% last year compared to 2019, while the number of citations from the regulator “’rose dramatically.’” The letter also singled out a slew of recalls by Indian drugmakers in recent months, as well as a number of plant closures in the U.S., both of which could further plunge the pharmaceutical supply chain into further uncertainty. Back in August, for instance, Alembic recalled more than 80,000 bottles of the bacterial eye infection treatment tobramycin, while the U.S. unit of India’s Aurobindo pulled 96 bottles of rufinamide tablets for treating seizure disorders. In both cases, the recalls were initiated due to the products being distributed throughout the U.S. without being approved. Elsewhere, Pfizer spent much of the second half of the year working with the FDA to right the ship at its Rocky Mount, North Carolina facility, which was damaged by a tornado this past summer. The House Committee has been investigating FDA’s foreign drug inspection program for some time. The committee says it sent a letter requesting information and documents in July, but as of mid-December, hasn’t received any response. Now, three committee members—Cathy Rodgers (R-WA), H. Morgan Griffith (R-VA) and Brett Guthrie (R-KY)—are seeking answers to nearly two-dozen questions around the FDA’s inspectional oversight, specifically concerning the agency’s operations in both China and India. They’re giving the FDA three weeks to respond. This isn’t the first time U.S. lawmakers have targeted the nation’s regulatory authority. Earlier this year, Republican leaders from the Energy and Commerce Committee separately pressed FDA Commissioner Califf to respond to questions on the FDA’s tracking of scarce medicines, its inspection priorities and what the agency has done to parse and prevent shortages for than half a dozen drugs. And in July, the ranking member of the Committee, Frank Pallone Jr. (D-NJ), urged House Republicans to take up legislation that would include FDA-related oversight in the reauthorization of the Pandemic and All-Hazards Prevention Act (PAHPA). Just last month, meanwhile, the chairman of the House Committee on Oversight and Accountability, James Comer (R-KY), and Lisa McClain (R-MI), chairwoman of the Subcommittee on Health Care and Financial Services, requested documents and a staff-level briefing from the FDA to parse through the agency’s shortage mitigation strategies.

Ad hoc announcement pursuant to Art. 53 LR Approval based on APPLY-PNH trial in adults with PNH and anemia despite prior anti-C5 treatment, and supported by the APPOINT-PNH study in complement inhibitor-naïve patients1-5 In APPLY-PNH, patients who switched to Fabhalta experienced superior increases of hemoglobin levels ≥ 2 g/dL (82.3% vs. 0%) and hemoglobin level ≥ 12 g/dL (67.7% vs. 0%), both in the absence of red blood cell transfusions, vs. patients who continued on anti-C5 treatment1,2 Fabhalta, now available for both previously treated and treatment-naïve patients, is the only FDA-approved Factor B inhibitor of the immune system’s complement pathway, which drives complement-mediated hemolysis in PNH1,6 Significant unmet need remains in PNH, a chronic and rare blood disorder; despite anti-C5 therapy, a large proportion of patients can remain anemic and dependent on blood transfusions7,8 Late-stage Fabhalta development program ongoing in multiple complement-mediated conditions Novartis today announced that the U.S. Food and Drug Administration (FDA) approved Fabhalta® (iptacopan) as the first oral monotherapy for the treatment of adults with paroxysmal nocturnal hemoglobinuria (PNH)1. Fabhalta is a Factor B inhibitor that acts proximally in the alternative complement pathway of the immune system, providing comprehensive control of red blood cell (RBC) destruction within and outside the blood vessels (intra- and extravascular hemolysis [IVH and EVH]). In clinical trials, treatment with Fabhalta increased hemoglobin levels (≥ 2 g/dL from baseline in the absence of RBC transfusions) in the majority of patients and in APPLY-PNH nearly all patients treated with Fabhalta did not receive blood transfusions1-5. “An efficacious oral treatment with a demonstrated safety profile could be practice-changing for physicians and help relieve burdens experienced by people with PNH,” said Vinod Pullarkat, MD, MRCP, Clinical Professor, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope. “In clinical studies, iptacopan was superior to anti-C5s in hemoglobin improvement in the absence of RBC transfusion and transfusion avoidance rate, and also effective in complement inhibitor-naïve individuals, by providing clinically meaningful hemoglobin-level increases without the need for blood transfusions.” The FDA approval is based on the Phase III APPLY-PNH trial in patients with residual anemia (hemoglobin 1,2. Approval was also supported by the Phase III APPOINT-PNH study in complement inhibitor-naïve patients1,3. The 24-week core treatment periods in APPLY-PNH and APPOINT-PNH trials respectively showed1-3: Patients with sustained increase of hemoglobin levels ≥ 2 g/dLa from baseline in the absence of transfusions: 82.3% of anti-C5-experienced Fabhalta patients responded vs. 0% for anti-C5 (difference of 81.5%b, Pc)1-3. Patients with sustained hemoglobin level ≥ 12 g/dLa in the absence of transfusions: 67.7% of anti-C5-experienced Fabhalta patients responded vs. 0% for anti-C5 (difference of 66.6%b, P1,2. Patients avoiding transfusiond,e: Transfusion avoidance rate 95.2% for anti-C5-experienced Fabhalta patients vs. 45.7% for anti-C5 (difference of 49.5%b, P1,2. In the APPLY-PNH trial, the most commonly reported (≥10%) adverse reactions (ARs) with Fabhalta vs. anti-C5s were: headachef (19% vs. 3%), nasopharyngitisg (16% vs. 17%), diarrhea (15% vs. 6%), abdominal painf (15% vs. 3%), bacterial infectionh (11% vs. 11%), nausea (10% vs. 3%), and viral infectioni (10% vs. 31%)1,2. In the APPOINT-PNH trial, the most commonly reported ARs (≥10%) were headachef (28%), viral infectioni (18%), nasopharyngitisg (15%), and rashj (10%)1,3. In APPLY-PNH, serious ARs were reported in two (3%) patients with PNH receiving Fabhalta, which included pyelonephritis, urinary tract infection and COVID-191,2. In APPOINT-PNH, serious ARs were reported in two (5%) patients with PNH receiving Fabhalta, which included COVID-19 and bacterial pneumonia1,3. Fabhalta may cause serious infections caused by encapsulated bacteria and is available only through a Risk Evaluation and Mitigation Strategy (REMS) that requires vaccinations for encapsulated bacteria1. People with PNH have an acquired mutation making red blood cells susceptible to premature destruction by the complement system6,8. PNH is characterized by hemolysis, bone marrow failure, and thrombosis in varying combinations and levels of severity6-8. Existing C5 inhibitor treatments, administered as infusions, may leave PNH symptoms uncontrolled7,8. Up to 88% of patients on anti-C5 treatment may have persistent anemia with over one-third of those patients requiring blood transfusions at least once per year7,8. “The U.S. approval of Fabhalta is an extraordinary moment for people living with PNH, their loved ones and the healthcare providers who care for them,” said Victor Bultó, President US, Novartis. “This new, effective oral medicine may mean that patients can reset their expectations of living with PNH, a chronic and life-altering blood disease. As Novartis continues to focus on conditions with unmet patient need, we are exploring the potential of Fabhalta in other complement-mediated diseases – with an ultimate goal to drive meaningful change for patients.” Discovered and developed by Novartis, Fabhalta is expected to be available in the United States in December. Additional regulatory filings and reviews for Fabhalta in PNH are currently underway around the world. Assessed between Day 126 and Day 168. bAdjusted difference in proportion. cSensitivity analysis incorporates data from local labs when central labs were not available. dAssessed between Day 14 and Day 168. eTransfusion avoidance is defined as absence of administration of packed-red blood cell transfusions between Day 14 and Day 168. fIncludes similar terms. gNasopharyngitis contains: rhinitis allergic, upper respiratory tract infection, pharyngitis, rhinitis. hBacterial infection contains: pyelonephritis, urinary tract infection, bronchitis bacterial, bronchitis haemophilus, cholecystitis, folliculitis, cellulitis, arthritis bacterial, sepsis, klebsiella infection, staphylococcal infection, Pseudomonas infection, hordeolum, pneumonia bacterial. iViral infection contains: COVID-19, herpes zoster, oral herpes, nasal herpes, influenza A virus test positive, influenza. jRash: dermatitis allergic, acne, erythema multiforme, rash maculo-papular, rash erythematous. APPLY-PNH (NCT04558918) was a Phase III, randomized, multinational, multicenter, active-comparator controlled, open-label trial to evaluate the efficacy and safety of twice-daily, oral Fabhalta monotherapy (200 mg) for the treatment of PNH by assessing if switching to Fabhalta was superior to continuing on anti-C5 therapies (US-approved and non-US-approved eculizumab and ravulizumab) in adult patients presenting with residual anemia (Hb 2,9. The trial enrolled 97 patients who were randomized in an 8:5 ratio to either twice-daily, oral Fabhalta monotherapy, or intravenous anti-C5 therapies (continuing with the same regimen as they were on prior to randomization)2,9. APPOINT-PNH (NCT04820530) was a Phase III, multinational, multicenter, open-label, uncontrolled single-arm study to evaluate the efficacy and safety of twice-daily, oral Fabhalta monotherapy (200 mg) in adult PNH patients who are naïve to complement inhibitor therapy, including anti-C5 therapies (eculizumab or ravulizumab)3,10. The trial enrolled 40 patients who received twice-daily, oral Fabhalta monotherapy3,10. PNH is a rare, chronic and serious complement-mediated blood disorder6. People with PNH have an acquired mutation in some of their hematopoietic stem cells (which are located in the bone marrow and can grow and develop into RBCs, white blood cells and platelets) that causes them to produce RBCs that are susceptible to premature destruction by the complement system6,8. This leads to intravascular hemolysis (destruction of RBCs within blood vessels) and extravascular hemolysis (destruction of RBCs mostly in the spleen and liver), which cause anemia (low levels of circulating RBCs), thrombosis (formation of blood clots) and other debilitating symptoms6,8. It is estimated that approximately 10-20 people per million worldwide live with PNH6. Although PNH can develop at any age, it is often diagnosed in people between 30-40 years old11,12. PNH has a significant unmet need not fully addressed by anti-C5 therapies (eculizumab or ravulizumab): despite treatment with anti-C5s, a large proportion of people with PNH may remain anemic, and dependent on blood transfusions6-8,13,14. Fabhalta (iptacopan) is an oral, Factor B inhibitor of the alternative complement pathway15-17. Fabhalta is indicated for the treatment of adults with paroxysmal nocturnal hemoglobinuria (PNH). Discovered at Novartis, Fabhalta is currently in development for a range of complement-mediated diseases including immunoglobulin A nephropathy (IgA nephropathy), C3 glomerulopathy (C3G), immune complex membranoproliferative glomerulonephritis (IC-MPGN) and atypical hemolytic uremic syndrome (aHUS). Based on disease prevalence, unmet needs and data from Phase II studies, Fabhalta has received FDA Breakthrough Therapy Designation in PNH, FDA Breakthrough Therapy Designation in C3G, orphan drug designations from the FDA and EMA in PNH and C3G, EMA PRIME designation for C3G, and EMA orphan drug designation in IgAN18-21. Novartis is an innovative medicines company. Every day, we work to reimagine medicine to improve and extend people’s lives so that patients, healthcare professionals and societies are empowered in the face of serious disease. Our medicines reach more than 250 million people worldwide. References Iptacopan Prescribing Information. East Hanover, NJ: Novartis Pharmaceuticals Corp; December 2023. Risitano AM, Rӧth A, Kulasekararaj A, et al. Oral Iptacopan Monotherapy Has Superior Efficacy to Anti-C5 Therapy in Patients with Paroxysmal Nocturnal Hemoglobinuria and Residual Anemia: Results From the Phase III APPLY-PNH Study. Presented at: 49th Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT); April 23-36, 2023; Paris, France. Risitano AM, Han B, Ueda Y, et al. Oral Complement Factor B Inhibitor Iptacopan Monotherapy Improves Hemoglobin to Normal/Near-Normal Levels in Paroxysmal Nocturnal Hemoglobinuria Patients Naïve to Complement Inhibitors: Phase III APPOINT-PNH Trial. Presented at: 49th Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT); April 23-36, 2023; Paris, France. Risitano AM, Röth A, Soret J, et al. Addition of iptacopan, an oral factor B inhibitor, to eculizumab in patients with paroxysmal nocturnal haemoglobinuria and active haemolysis: an open-label, single-arm, phase 2, proof-of-concept trial. Lancet Haematol. 2021;8(5):e344-e354. doi:10.1016/S2352-3026(21)00028-4 Jang JH, Wong L, Ko BS, et al. Iptacopan monotherapy in patients with paroxysmal nocturnal hemoglobinuria: a 2-cohort open-label proof-of-concept study. Blood Adv. 2022;6(15):4450-4460. doi:10.1182/bloodadvances.2022006960 Cançado RD, Araújo A da S, Sandes AF, et al. Consensus statement for diagnosis and treatment of paroxysmal nocturnal haemoglobinuria. Hematol Transfus Cell Ther. 2021;43(3):341-348. doi:10.1016/j.htct.2020.06.006 McKinley CE, Richards SJ, Munir T, et al. Extravascular Hemolysis Due to C3-Loading in Patients with PNH Treated with Eculizumab: Defining the Clinical Syndrome. Blood. 2017;130(Supplement 1):3471. doi:10.1182/blood.V130.Suppl_1.3471.3471 Dingli D, Matos JE, Lehrhaupt K, et al. The burden of illness in patients with paroxysmal nocturnal hemoglobinuria receiving treatment with the C5-inhibitors eculizumab or ravulizumab: results from a US patient survey. Ann Hematol. 2022;101(2):251-263. doi:10.1007/s00277-021-04715-5 Novartis Pharmaceuticals. A Randomized, Multicenter, Active-Comparator Controlled, Open-Label Trial to Evaluate Efficacy and Safety of Oral, Twice Daily LNP023 in Adult Patients With PNH and Residual Anemia, Despite Treatment With an Intravenous Anti-C5 Antibody. clinicaltrials.gov; 2022. Accessed September 21, 2022. https://clinicaltrials.gov/ct2/show/NCT04558918 Novartis Pharmaceuticals. A Multicenter, Single-Arm, Open-Label Trial to Evaluate Efficacy and Safety of Oral, Twice Daily Iptacopan in Adult PNH Patients Who Are Naive to Complement Inhibitor Therapy. clinicaltrials.gov; 2022. Accessed September 21, 2022. https://clinicaltrials.gov/ct2/show/NCT04820530 Hill A, DeZern AE, Kinoshita T, Brodsky RA. Paroxysmal nocturnal haemoglobinuria. Nat Rev Dis Primer. 2017;3(1):17028. doi:10.1038/nrdp.2017.28 Schrezenmeier H, Röth A, Araten DJ, et al. Baseline clinical characteristics and disease burden in patients with paroxysmal nocturnal hemoglobinuria (PNH): updated analysis from the International PNH Registry. Ann Hematol. 2020;99(7):1505-1514. doi:10.1007/s00277-020-04052-z Debureaux PE, Kulasekararaj AG, Cacace F, et al. Categorizing hematological response to eculizumab in paroxysmal nocturnal hemoglobinuria: a multicenter real-life study. Bone Marrow Transplant. 2021;56(10):2600-2602. doi:10.1038/s41409-021-01372-0 Debureaux PE, Cacace F, Silva BGP, et al. Hematological Response to Eculizumab in Paroxysmal Nocturnal Hemoglobinuria: Application of a Novel Classification to Identify Unmet Clinical Needs and Future Clinical Goals. Blood. 2019;134(Supplement_1):3517-3517. doi:10.1182/blood-2019-125917 Schubart A, Anderson K, Mainolfi N, et al. Small-molecule factor B inhibitor for the treatment of complement-mediated diseases. Proc Natl Acad Sci. 2019;116(16):7926-7931. doi:10.1073/pnas.1820892116 Barratt J, Rovin B, Zhang H, et al. POS-546 EFFICACY AND SAFETY OF IPTACOPAN IN IgA NEPHROPATHY: RESULTS OF A RANDOMIZED DOUBLE-BLIND PLACEBO-CONTROLLED PHASE 2 STUDY AT 6 MONTHS. Kidney Int Rep. 2022;7(2):S236. doi:10.1016/j.ekir.2022.01.577 Rizk DV, Rovin BH, Zhang H, et al. Targeting the Alternative Complement Pathway With Iptacopan to Treat IgA Nephropathy: Design and Rationale of the APPLAUSE-IgAN Study. Kidney Int Rep. 2023;8(5):968-979. doi:10.1016/j.ekir.2023.01.041 The content above comes from the network. if any infringement, please contact us to modify.

RTI International congratulates Lao PDR in eliminating LF — a disabling disease impacting the lives of millions of people around the world RESEARCH TRIANGLE PARK, N.C., Oct. 18, 2023 /PRNewswire/ -- RTI International, a nonprofit research institute and leading international development organization, joins the Lao People's Democratic Republic (Lao PDR), World Health Organization, and the U.S. Agency for International Development (USAID) in celebrating Lao PDR's achievement of eliminating lymphatic filariasis as a public health problem. Also known as elephantiasis, lymphatic filariasis is a neglected tropical disease (NTD) that can cause swollen extremities in a person and lead to severe disfigurement and disability, as well as social and economic discrimination against those affected. As of the latest data released by WHO last week, more than 793 million people required treatment for this disease across 44 countries in Asia, Africa, the Western Pacific, and parts of the Caribbean and South America. WHO officially confirmed this week that the people of Lao PDR are no longer at risk of contracting the disease. "RTI sends our sincerest congratulations to the government of Lao PDR and its people for solving this pressing public health problem," said Tim Gabel, president and CEO of RTI International. "It is particularly significant given that Lao PDR achieved the elimination of trachoma as public health problem in 2017, demonstrating the power of national commitment to ending neglected tropical diseases." RTI supported this milestone through its leadership of USAID's Act to End NTDs | East program, which has advanced the sustainable control and elimination of NTDs in 13 countries across Africa, Asia and Latin America. RTI worked with the government of Lao PDR to compile the data and information needed to establish proof that the country had eliminated lymphatic filariasis as a public health problem. Additionally, with USAID support, RTI assisted the government to develop a plan to monitor and track progress against the disease to ensure elimination is sustained in the future. "Lao PDR is the latest example of a country that worked hard to go the last mile to reach lymphatic filariasis elimination and free its people from this disabling disease," said  Lisa Rotondo, Director of USAID's Act to End NTDs | East program at RTI. "Global momentum towards eliminating lymphatic filariasis as a public health problem, led by countries themselves, is only growing. We are proud to be among the partners that supported the Lao PDR Ministry of Health to achieve this important milestone for its people." The elimination of lymphatic filariasis in Lao PDR was supported by many partners including USAID, RTI, FHI360, WHO, Mac Foundation, and the Asian Development Bank. In addition, albendazole treatments were donated by GlaxoSmithKline through the WHO donation program for NTD medicines. The Southeast Asian country now becomes the 19th country to have achieved validation of lymphatic filariasis elimination, marking another important public health milestone for the country and globally. Recently, Bangladesh also eliminated lymphatic filariasis with support from the Act to End NTDs | East program, led by RTI. Learn more about RTI's work to control and eliminate NTDs around the globe Media Contact: Kerry Branon 919 708-8205 [email protected] SOURCE RTI International