Over the course of the past several months, the COVID-19 pandemic has rapidly progressed, bringing broad societal and economic impacts along with immediate health concerns. While the situation is still evolving and long-term effects are not yet clear, the rare and orphan disease development sector has already been affected through changes in demand, supply chain, development hurdles, policy, and more. Some key points to be aware of include ways in which rare disease drugs and stakeholders have expanded their scope to address COVID-19, how the Orphan Drug Designation was brought into the limelight, and how interruptions to medical research and supply chain have been introduced due to stay-at-home orders for the global workforce. Despite these challenges, the demand for orphan drugs has not decreased, and the needs in this area remain urgent.
Industry Expansion to COVID-19 Several companies with interests in the rare disease space are expanding to examine indications for COVID-19. Alexion Pharmaceuticals will be examining potential COVID-19 response in their drug Ultomiris, currently FDA-approved for two rare diseases: atypical hemolytic uremic syndrome and paroxysmal nocturnal hemoglobinuria.[1] The mechanism of C5 inhibition shows potential for use in severe COVID-19 pneumonia.[2] A Phase 3 trial was set to begin this month, with intent to enroll 270 patients currently hospitalized for COVID-19.[3][4] Other companies with focuses on rare diseases, such as Eiger BioPharmaceuticals and Sarepta Therapeutics, are also expanding to develop potential COVID-19 treatments. Eiger BioPharmaceuticals announced that it will begin a Phase 2 trial for peginterferon lambda (Lambda) enrolling 120 patients with mild COVID-19 to assess whether Lambda is effective in limiting duration of SARS-CoV-2 viral shedding. Lambda currently holds both FDA and EMA Orphan Drug Designation for hepatitis D (HDV).[5] Serapta Therapeutics, often focused on rare genetic diseases such as Duchenne muscular dystrophy, has revived its anti-viral program to develop a therapy intended to interfere with the SARS-CoV-2 replication process.[6][7] Most recently, Open Orphan and its subsidiary company Hvivo have entered into an exclusive arrangement with Quotient to carry out COVID-19 antibody testing.[8] According to their websites, these companies believe that their additional efforts to research COVID-19 should not impact available supply of their products for current rare disease patients.[9][10][11] However, in Russia, the impacts of COVID-19 needs on the drug market have already resulted in decreased availability of orphan drugs.[12] The US also has seen hydroxychloroquine shortages due to use for COVID-19, impacting patients with lupus, rheumatoid arthritis, and autoimmune diseases who typically rely on this medication for their treatment.[13] Remsdesivir and the Orphan Drug Designation The Orphan Drug Designation was briefly granted to Gilead for remsdesivir at a point when cases in the United States remained below the 200,000 threshold, but this development brought controversy on whether the orphan drug classification was appropriate for COVID-19 given the rapid increases in case numbers, along with concerns around pricing and exclusivity.[14][15] Gilead responded to these concerns by requesting that the FDA rescind this status, stating that they had determined that they would not require the designation to continue with rapid development to meet evolving COVID-19 needs.[16][17][18] The discussion around whether remsdesivir merited consideration under the Orphan Drug Act prompted broader scrutiny around the act and its policies around regulating the orphan market;[19] however, no immediate impacts from this conversation appear forthcoming. Interruption and Changes for Lab Research and Clinical Trials The COVID-19 pandemic has led to a halt in some research activities around rare diseases, such as interruption of lab work and clinical trials. For example, FOXG1 researchers at the University of Buffalo spoke about their concerns over lost time in the lab, especially given that the treatments they research have potential to reshape their own daughter’s life.[20] Parents of other children with rare diseases have also spoken out about the trials that have been indefinitely postponed or cancelled, following National Institutes of Health (NIH) staffing cuts and stay-at-home restrictions.[21] Reasons that clinical trials might be paused are numerous, ranging from challenging logistics of in-person follow-up visits and therapeutic administration, potential exposure of vulnerable rare disease patients to infectious COVID-19 patients at shared clinics, and loss of available clinical investigators currently shifting focus from rare disease to COVID-19 development.[22] However, some researchers and families have found creative ways to continue engaging in clinical research despite the challenges created by the COVID-19 pandemic. One family with three children enrolled in a NIH gene therapy trial for a rare, fatal disease managed to re-arrange travel plans from their home in Sweden to trial headquarters in Maryland in a two-day window in order to arrive before travel from Europe was halted.[23] Other studies, when possible, have been able to continue using telemedicine consults and mailed pharmaceuticals.[24] Effects on Pharmaceutical Supply Chain With its global reach, the COVID-19 pandemic has inevitably had effects cascading across the pharmaceutical supply chain. Even before COVID-19, the FDA had noted drug shortages for almost 150 pharmaceutical supply products. Given the labor-intensive nature of pharmaceutical development, coupled with a reliance on highly skilled workers, the impact of widescale worker absences due to global stay-at-home directives can be deeply felt.[25] Much of the production for raw materials and active pharmaceutical ingredients takes place in China, and as the outbreak spread from Wuhan around the country production slipped by as much as 10% to 20%.[26] As China’s lockdown is lifted, production is returning, but delays may still be felt given the challenges involved with international shipping. India also has needed to halt production, in part to address their own outbreak and in part due to absence of raw materials typically imported from China. Given that India supports products for over half of US generic drug needs, these shortages can have a long-lasting impact on US supply chain durability.[26] Despite these concerns, the chain appears relatively intact as of April. The staggered nature of the COVID-19 pandemic peaks around the globe have allowed for production to continue to a strong extent. However, the true impact of the pandemic on the supply chain may not be clear for months.[27] A Stable and Increasing Demand Despite the societal impacts of COVID-19, the needs for rare disease development remain stable. Additionally, as treatments traditionally employed for rare disease patients show promise for COVID-19 and companies most commonly focused on orphan drugs join the race to find a cure or vaccine, the demand for products in the rare disease sector may even see an increase. BluePrint Orphan Are you a rare disease company seeking to navigate these complicated times? Reach out to BluePrint Orphan for analytical support in market research, epidemiology, drug forecasting, and business development. Sources [1] Taylor P. Alexion will test rare disease drug Ultomiris in severe COVID-19. PMLive. https://www.pmlive.com/pharma_news/alexion_will_test_rare_disease_drug_ultomiris_in_severe_covid-19_1338682. Published April 21, 2020. Accessed April 30, 2020. [2] Alexion Announces Plans to Initiate Phase 3 Study of ULTOMIRIS® (ravulizumab-cwvz) in Hospitalized Patients with Severe COVID-19. Alexion Pharmaceuticals, Inc. https://alexionpharmaceuticalsinc.gcs-web.com/news-releases/news-release-details/alexion-announces-plans-initiate-phase-3-study-ultomirisr. Accessed April 30, 2020. [3] Nathan-Kazis J. Alexion Will Test Rare Disease Drug in Covid-19 Patients. https://www.barrons.com/articles/alexion-to-test-rare-disease-drug-in-covid-19-patients-51587395828. Accessed May 1, 2020. [4] Staines R. Alexion trials rare disease drug Ultomiris in severe COVID-19 cases. Published April 21, 2020. Accessed May 1, 2020. https://pharmaphorum.com/news/alexion-trials-rare-disease-drug-ultomiris-in-severe-covid-19-cases/ [5] Eiger BioPharmaceuticals Announces First COVID-19 Patients Dosed with Peginterferon Lambda. P&T Community. https://www.ptcommunity.com/wire/eiger-biopharmaceuticals-announces-first-covid-19-patients-dosed-peginterferon-lambda. Published April 30, 2020. Accessed May 1, 2020. [6] Bary A. Sarepta Therapeutics Revives Anti-Viral Program for Covid-19. Accessed May 1, 2020. https://www.nasdaq.com/articles/sarepta-therapeutics-revives-anti-viral-program-for-covid-19-2020-04-29 [7] AP News. Sarepta Therapeutics Announces Research Agreement with U.S. Department of Defense to Evaluate Multiple Constructs From its Proprietary RNA Platform as Treatments for COVID-19. AP NEWS. Published April 28, 2020. Accessed May 1, 2020. https://apnews.com/35ca9dec9019430be4c0b6f41432825d [8] Donnelly E. Open Orphan enters Covid-19 antibody testing partnership. Independent. Accessed May 19, 2020. https://www.independent.ie/business/irish/open-orphan-enters-covid-19-antibody-testing-partnership-39195669.html [9] Alexion Pharmaceuticals. Covid 19 Response. https://alexion.com. Accessed May 8, 2020. https://alexion.com [10] Sarepta Therapeutics. COVID-19 Resources for Patients and Families. Accessed May 8, 2020. https://www.sarepta.com/community-update-covid-19 [11] Eiger BioPharmaceuticals. Eiger BioPharmaceuticals Provides Update on Clinical Development Activities and Business Operations During COVID-19 Pandemic. EigerBio. Published April 3, 2020. Accessed May 8, 2020. http://www.eigerbio.com/eiger-biopharmaceuticals-provides-update-on-clinical-development-activities-and-business-operations-during-covid-19-pandemic/ [12] COVID-19 leading to shortage of orphan drugs in Russia. Accessed May 8, 2020. https://www.thepharmaletter.com/article/covid-19-leading-to-shortage-of-orphan-drugs-in-russia [13] Mehta B, Salmon J, Ibrahim S. Potential Shortages of Hydroxychloroquine for Patients with Lupus During the Coronavirus Disease 2019 Pandemic. JAMA Health Forum. 2020;1(4):e200438-e200438. doi:10.1001/jamahealthforum.2020.0438 [14] Brennan Z. Gilead’s Orphan Drug Designation for COVID-19 Antiviral Raises Questions. Accessed May 8, 2020. https://www.raps.org/news-and-articles/news-articles/2020/3/gileads-orphan-drug-designation-for-covid-19-antiv [15] Letter from 50 groups to Gilead renounce remdesivir orphan drug claim. Public Citizen. Accessed May 8, 2020. https://www.citizen.org/wp-content/uploads/Letter-from-50-groups-to-Gilead-renounce-remdesivir-orphan-drug-claim.pdf?eType=EmailBlastContent&eId=f4140734-e5c9-45b8-b67a-d43a461609bf. [16] Gilead. Gilead Sciences Statement on Request to Rescind Remdesivir Orphan Drug Designation. Accessed May 8, 2020. https://www.gilead.com/news-and-press/company-statements/gilead-sciences-statement-on-request-to-rescind-remdesivir-orphan-drug-designation [17] Gilead to Rescind Orphan Drug Status for Remdesivir, a Potential COVID-19 Treatment. Drug Topics. Published March 27, 2020. Accessed May 8, 2020. https://www.drugtopics.com/article/gilead-rescind-orphan-drug-status-remdesivir-potential-covid-19-treatment [18] Keown A. Following Outcry, Gilead Sciences Seeks to Rescind Orphan Drug Designation for COVID-19 Drug. BioSpace. Accessed May 8, 2020. https://www.biospace.com/article/following-outcry-gilead-sciences-seeks-to-rescind-orphan-drug-designation-for-covid-19-drug/ [19] Lane M. COVID-19: Time to reexamine the Orphan Drug Act and find an alternative. TheHill. Published April 25, 2020. Accessed May 8, 2020. https://thehill.com/opinion/healthcare/494172-covid-19-time-to-reexamine-the-orphan-drug-act-and-find-an-alternative [20] Hsu C. For two UB scientists, love means studying their daughter’s rare disease. University at Buffalo. Accessed May 8, 2020. http://www.buffalo.edu/news/releases/2020/05/001.html [21] Vergano D. These Kids With Rare Genetic Diseases Were Part Of Research Into New Treatments. The Coronavirus Has Stopped All Of It. BuzzFeed News. Accessed May 1, 2020. https://www.buzzfeednews.com/article/danvergano/coronavirus-rare-disease-children-research [22] Underwood G. Surviving as a rare disease biotech during COVID-19 -. Published May 12, 2020. Accessed May 19, 2020. https://pharmaphorum.com/r-d/views-analysis-r-d/surviving-as-a-rare-disease-biotech-during-covid-19/ [23] Vargas T. Their three children have a fatal disease, and they refused to let the coronavirus take away their only chance at saving them. Washington Post. Accessed May 8, 2020. https://www.washingtonpost.com/local/their-three-children-have-a-fatal-disease-and-they-refused-to-let-the-coronavirus-take-away-their-only-chance-at-saving-them/2020/04/24/87124d46-865b-11ea-ae26-989cfce1c7c7_story.html [24] Lupkin S. Coronavirus Pandemic Brings Hundreds Of U.S. Clinical Trials To A Halt. NPR.org. Accessed May 8, 2020. https://www.npr.org/sections/health-shots/2020/04/11/832210606/coronovirus-pandemic-brings-hundreds-of-u-s-clinical-trials-to-a-halt [25] Keskinocak P, Ozkaya E. US pharmaceutical supply chain unprepared for COVID-19. Published April 27, 2020. Accessed May 8, 2020. https://www.healio.com/primary-care/practice-management/news/online/{c332e14e-d73a-49f9-8cb2-a7ab16343ff1}/us-pharmaceutical-supply-chain-unprepared-for-covid-19 [26] Gandayuwana I. COVID-19: A double-edged sword for the pharma industry. Scienceboard.net. Accessed May 8, 2020. https://www.scienceboard.net/index.aspx?sec=ser&sub=def&pag=dis&ItemID=700 [27] Mullin R. COVID-19 is reshaping the pharmaceutical supply chain. Chemical & Engineering News. Accessed May 8, 2020. https://cen.acs.org/business/outsourcing/COVID-19-reshaping-pharmaceutical-supply/98/i16 Comments are closed.
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