There are more than 7,000 rare diseases that affect hundreds of millions of people worldwide. As Rare Disease Day is observed on February 28, here are five recent advancements that have transformed research and boosted the scope for the development of novel therapies.\n\n\n\n FDA approves tissue-agnostic therapies for rare cancers\n\n\n\nTissue-agnostic drug development has been crucial in cancer therapy research, where a specific molecular alteration is targeted. This method has influenced therapy research in rare diseases and cancers like renal cell carcinoma, a form of kidney cancer. In 2022, the U.S. Food and Drug Administration (FDA) approved a combination of dabrafenib and trametinib for tumors with a specific mutation in the BRAF gene, which has broadened the scope for drug development for rare cancers.\n\n\n\nThe drug combination of dabrafenib and trametinib blocks the signals that promote the proliferation of tumor cells which are activated by the BRAF mutation. Dabrafenib inhibits signals from the BRAF protein, whereas trametinib is an inhibitor to signals from the MEK protein, to stop the growth of tumor cells.\n\n\n\nMarjorie Zettler, executive director of clinical science at Regor Pharmaceuticals Inc., a biopharmaceutical company that specializes in oncology and auto-immune diseases, said: “While the standard approach has been to conduct clinical trials and seek regulatory approval in one indication at a time defined by the affected organ or site, clinical trials for tissue-agnostic drugs enroll patients with any tumor that has the molecular alteration of interest, independent of the tumor’s location.\n\n\n\n “This more efficient strategy is of particular benefit for rare cancers, where the small number of patients makes traditional clinical trials difficult or unfeasible.”\n\n\n\nSuccess in ongoing clinical trials for uveal cancer therapy \n\n\n\nThe drug roginolisib developed by the clinical-stage rare disease company iOnctura has shown safe and specific tumor reduction and disease stabilization in patients with metastatic uveal melanoma and other rare cancers, as of December 2022.\n\n\n\nUveal melanoma, a disease that affects around 7,000 people every year, originates in the tissues of the eye, causing symptoms such as blurred vision. Due to limited treatment options, the projected overall survival is only a year in cases after the cancer metastases, which occurs in around 50% of the patients.\n\n\n\nAccording to Catherine Pickering, chief executive officer of iOnctura, roginolisib has influenced rare cancer research by showing signs of clinical efficacy in this disease. Part A of the phase 1 study investigated the safety and pharmacokinetics of continuous daily dosing of the drug at 10, 20, 40 and 80 mg in 38 cancer patients. \n\n\n\n“Part B is an ongoing cohort-expansion of the biologically-effective dose (BED) of 80mg in solid and hematologic malignancies including a recently opened non-Hodgkin´s lymphoma cohort,” said Pickering.\n\n\n\nRoginolisib, which is an allosteric modulator of PI3Kδ, was granted Orphan Drug Status by the FDA, which allows benefits during development and commercialization.\n\n\n\n“Certain solid and hematological tumor cells upregulate PI3Kδ to drive intrinsic survival pathways and to orchestrate a dampening of the host’s immune response. By inhibiting PI3Kδ, key survival pathways are blocked, and immune suppression reversed. This offers a powerful and safe dual approach to destroying certain tumors through precision inhibition of one key target,” said Pickering.\n\n\n\nThe drug’s success so far has led to the possibility of starting a phase Ib trial in first line myelofibrosis, another rare cancer that causes scarring of the bone marrow, later this year. \n\n\n\nEuropean Commission approves first gene therapy for hemophilia B\n\n\n\nThe European Commission has approved the first one-time gene therapy Hemgenix, distributed by biotech company CSL Behring in February following the FDA’s approval in November last year.\n\n\n\nHemophilia B is a rare genetic bleeding disorder that affects individuals with insufficient levels of the protein Factor IX, which is necessary for blood clotting to promote healing. The X-linked disorder affects 1 in 25,000 male births.\n\n\n\nPhase 3 of the clinical trials treated hemophilia B patients who were previously undergoing prophylactic therapy, with a single intravenous infusion of Hemgenix. This led to a 64% reduction of the annualized bleed rate, which indicated the efficacy of the therapy. \n\n\n\nBill Mezzanotte, head of research and development and chief medical officer at CSL said: “The approval of Hemgenix in Europe is the essence of great science delivering a medicine that we believe can transform the treatment paradigm for both people living with hemophilia B and the healthcare professionals who treat them.”\n\n\n\nAs current treatment for moderate to severe hemophilia is typically life-long prophylactic infusions to supplement low levels of Factor IX, Wolfgang Miesbach, head of coagulation disorders at the Comprehensive Care Center at University Hospital of Frankfurt said the results of the trial demonstrates that Hemgenix has the potential to eliminate the need for routine prophylaxis. \n\n\n\nMiesbach said: “This approval marks an important step forward in the treatment of hemophilia B, which could be transformative for people who are debilitated by bleeds into their muscles, joints and internal organs, alleviating the burden of lifelong intravenous infusions of Factor IX products.”\n\n\n\nFabry disease research: Enzyme therapy for this rare disease recommended for marketing authorization\n\n\n\nA novel recombinant enzyme used in the treatment of Fabry disease has been recommended for marketing authorization by the European Medicines Agency’s Committee for Medicinal Products for Human Use.\n\n\n\nDeveloped by international bio-pharma company Chiesi Global Rare Diseases in partnership with Israeli biopharma company Protalix BioTherapeutics, Inc., PRX-102 is the first pegylated enzyme being investigated as an enzyme replacement therapy for Fabry disease. The disease affects fat metabolism due to the deficient activity of the enzyme α-galactosidase A, and can cause kidney and heart failure.\n\n\n\nThe recommendation came after successful preclinical and clinical trials that evaluated PRX-102, which is a plant cell culture-expressed and chemically modified version of the recombinant alpha-galactosidase A enzyme. \n\n\n\n“We believe that this recommendation further recognizes the strength of the positive dataset from our robust clinical trial program and underscores the potential for PRX-102 to provide a new treatment option for patients with Fabry disease,” said Dror Bashan, president and chief executive officer of Protalix. \n\n\n\n“Data from our clinical program indicates that PRX-102 has the potential to be a long-lasting therapy with a favorable tolerability and immunogenicity profile,” said Bashan.\n\n\n\nDanon disease research: FDA grants Regenerative Medicine Advanced Therapy Designation to first cardiac gene therapy for this rare disease\n\n\n\nThe FDA has granted Regenerative Medicine Advanced Therapy (RMAT) Designation to the first cardiac gene therapy for the treatment of Danon disease, in February 2023.\n\n\n\nThis rare X-linked genetic disorder is caused by mutations in the gene encoding lysosome-associated membrane protein 2 (LAMP-2), an important mediator of autophagy. The disease leads to the dysfunction in heart, muscle and brain cells. \n\n\n\nThe therapy, which has been developed by clinical-stage biotech company Rocket Pharmaceuticals, is currently in phase 2 of clinical trials after obtaining positive safety and efficacy results from phase 1 trials. \n\n\n\nGaurav Shah, the chief executive officer of Rocket Pharma expressed that this “is another important step forward, both for patients with Danon Disease and for the gene therapy field.” \n\n\n\nAn RMAT designation provides FDA support for and expedites drug development, and is given to therapies that have been evidenced to treat life-threatening diseases.