Edition of 15 December 2023

A new article has been published in the Orphanet Journal of Rare Diseases which examines the efficacy and safety of compassionate use for rare disease drugs. Using a literature review covering the period from 1991 to 2022, researchers determined that while compassionate use is an important treatment option for patients with rare diseases, better monitoring tools are needed in order to ensure its safety.

Compassionate use is a system by which patients can obtain access to drugs which have not yet been approved, often which are still in the clinical trial stage. It is typically applied in the case of patients with serious, life-threatening conditions with no alternative treatments – often rare diseases. Regulatory bodies around the world, such as the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) have their own specific compassionate use procedures.

Since compassionate use occurs before substantial safety and efficacy data is available, this study sought to determine to what extent rare disease drugs accessed in this manner helped patients, and the rates and which patients experienced adverse effects of varying severity. Based on their analysis, the authors determined that compassionate use was an important and relatively effective treatment option for rare diseases. However, they identified challenges in evaluating safety of the drugs due to a lack of available data and inconsistencies in reporting adverse effects. Therefore, they recommend the creation of adverse event reporting systems which are specific to compassionate use.

In July, the EMA's CHMP delivered three positive opinions on market authorisation to the following medicinal products with an orphan designation:

• Talvey, for the treatment of adult patients with relapsed and refractory multiple myeloma
• Tepkinly, for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma
• Tevimbra, for the treatment of adult patients with unresectable, locally advanced or metastatic oesophageal squamus cell carcinoma after prior platinum-based chemotherapy

In August, the CHMP did not deliver any positive opinions on market authorisation to medicinal products with an orphan designation.

In September, the CHMP delivered four positive opinions on market authorisation to the following medicinal products with an orphan designation:

• Finlee, for the treatment of glioma
• Vanflyta, for the treatment of adult patients with diagnosed acute myeloid leukaemia
• Yorvipath, for the treatment of chronic hypoparathyroidism in adults
• Zilbrysq, for the treatment of generalised myasthenia gravis in adults

In October, the CHMP delivered four positive opinions on market authorisation to the following medicinal products with an orphan designation:

• Agamree, for the treatment of Duchenne muscular dystrophy
• Elrexfio, for the treatment of adult patients with relapsed or refractory multiple myeloma
• Loargys, in exceptional circumstances for the treatment of hyperargininemia
• Rezzayo, for the treatment of invasive candidiasis

In November, the CHMP delivered three positive opinions on market authorisation to the following medicinal products with an orphan designation:

• Omjjara, for the treatment of myelofibrosis
• Rystiggo, for the treatment of generalised myasthenia gravis
• Spexotras, for the treatment of paediatric patients aged one year and older with glioma

In July, the FDA accorded market authorisation to the following medicinal products with an orphan designation:

• Balfaxar, for urgent reversal of acquired coagulation factor deficiency induced by Vitamin K antagonist (VKA, e.g., warfarin) therapy in adult patients with need for an urgent surgery/invasive procedure
• Vanflyta, in combination with standard cytarabine and anthracycline induction and cytarabine consolidation, and as maintenance monotherapy following consolidation chemotherapy, for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) that is FLT3 internal tandem duplication (ITD)-positive as detected by an FDA-approved test
• Cyfendus, as post-exposure prophylaxis of disease following suspected or confirmed exposure to Bacillus anthracis in persons 18 through 65 years of age when administered in conjunction with recommended antibacterial drugs

In August, the FDA accorded market authorisation to the following medicinal products with an orphan designation:

• Reblozyl, for treatment of anemia without previous erythropoiesis stimulating agent use (ESA-naive) in adult patients with very low- to intermediate-risk myelodysplastic syndromes (MDS) who may require regular red blood cell (RBC) transfusions
• Ingrezza, for treatment of adults with chorea associated with Huntington's disease
• Veopoz, for treatment of adult and pediatric patients 1 year of age and older with CD55-deficient protein-losing enteropathy (PLE), also known as CHAPLE disease
• Sohonos, for the reduction in volume of new heterotopic ossification in adults and pediatric patients aged 8 years and older for females and 10 years and older for males with fibrodysplasia ossificans progressiva (FOP)
• Elrexfio, for treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody
• Hepzato, as a liver-directed treatment for adult patients with uveal melanoma with unresectable hepatic metastases affecting less than 50% of the liver and no extrahepatic disease or extrahepatic disease limited to the bone, lymph nodes, subcutaneous tissues, or lung that is amenable to resection or radiation
• Daxxify, for treatment of cervical dystonia in adult patients
• Talvey, for treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody

In September, the FDA accorded market authorisation to the following medicinal products with an orphan designation:

• Rivfloza, to lower urinary oxalate levels in children 9 years of age and older and adults with primary hyperoxaluria type 1 (PH1) and relatively preserved function, e.g., eGFR greater than or equal to 30 mL/min/1.73 m2
• Opfolda, in combination with Pombiliti, for the treatment of adult patients with late-onset Pompe disease (lysosomal acid alpha-glucosidase [GAA] deficiency) weighing greater than or equal to 40 kg and who are not improving on their current enzyme replacement therapy (ERT)
• Pombiliti, in combination with Opfolda, for the treatment of adult patients with late-onset Pompe disease (lysosomal acid alpha-glucosidase [GAA] deficiency) weighing greater than or equal to 40 kg and who are not improving on their current enzyme replacement therapy (ERT)
• Bosulif, for treatment of pediatric patients 1 year of age and older with chronic phase (CP) Philadelphia chromosome positive chronic myelogenous leukemia (Ph+ CML), newly-diagnosed or resistant or intolerant to prior therapy
• Ojjaara, for treatment of intermediate or high-risk myelofibrosis (MF), including primary MF or secondary MF [post-polycythemia vera (PV) and post-essential thrombocythemia (ET)], in adults with anemia
• Aphexda, in combination with filgrastim (G-CSF) to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with multiple myeloma
• Xalkori, for treatment of adult and pediatric patients 1 year of age and older with unresectable, recurrent, or refractory inflammatory myofibroblastic tumor (IMT) that is ALK-positive
• Xalkori, for treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK) or ROS1-positive as detected by an FDA-approved test
• Xalkori, for treatment of pediatric patients 1 year of age and older and young adults with relapsed or refractory, systemic anaplastic large cell lymphoma (ALCL) that is ALK-positive

In October, the FDA accorded market authorisation to the following medicinal products with an orphan designation:

• Keytruda, in combination with gemcitabine and cisplatin, for the treatment of patients with locally advanced unresectable or metastatic biliary tract cancer (BTC)
• Loqtorzi, in combination with cisplatin and gemcitabine, for the first-line treatment of adults with metastatic or with recurrent, locally advanced nasopharyngeal carcinoma (NPC); and as a single agent, for the treatment of adults with recurrent unresectable or metastatic NPC with disease progression on or after a platinum-containing chemotherapy
• Agamree, for treatment of Duchenne muscular dystrophy (DMD) in patients 2 years of age and older
• Tibsovo, for treatment of adult patients with relapsed or refractory myelodysplastic syndromes (MDS) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test
• Rozlytrek, for the treatment of adult and pediatric patients 12 years of age and older with solid tumors that have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity, and have either progressed following treatment or have no satisfactory alternative therapy
• Voxzogo, to increase linear growth in pediatric patients with achondroplasia with open epiphyses
• Zilbrysq, for treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) antibody positive
• Opdivo, as adjuvant treatment of adult and pediatric patients 12 years of age and older with completely resected Stage IIB, Stage IIC, Stage III, or Stage IV melanoma
• Braftovi, in combination with binimetinib, for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) with a BRAF V600E mutation, as detected by an FDA-approved test

In November, the FDA accorded market authorisation to the following medicinal products with an orphan designation:

• Ogsiveo, for adult patients with progressing desmoid tumors who require systemic treatment
• Keytruda, in combination with fluoropyrimidine- and platinum-containing chemotherapy, for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma
• Augtyro, for treatment of adult patients with locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC)
• Adzynma, as prophylactic or on demand enzyme replacement therapy (ERT) in adult and pediatric patients with congenital thrombotic thrombocytopenic purpura (cTTP)