New Medicines

Fanconi anaemia (FA)


New molecular entity
Rocket Pharmaceuticals
Rocket Pharmaceuticals

Development and Regulatory status

Phase II Clinical Trials
Phase II Clinical Trials
May 22Following positive data from pivotal PII trial, Rocket Pharmaceuticals announced they are initiating dialogue with health authorities on next steps forward.[8]
Dec 19PRIME designation was based on data from patients treated with RP-L102 Process A. The registrational Phase 2 trial of RP-L102 is currently ongoing and in this patients will be treated with RP-L102 Process B which incorporates a modified stem cell enrichment process, transduction enhancers, as well as commercial-grade vector and final drug product. The primary endpoint, which has been agreed upon by both the EMA and FDA will be the emergence of MMC-resistance, a measure of phenotypic correction, in bone marrow cells [4].
Dec 19EMA granted PRIority MEdicines (PRIME) eligibility to RP L102 [3].
Nov 18FDA grants regenerative medicine advanced therapy (RMAT) and fast track designations to RP L102 for the treatment of FA. RMAT designation was granted based on the positive efficacy and safety results from the ongoing PI/II trial [3].
Oct 18Granted orphan drug status in EU and US [3].
Jul 18FDA grants Rare Paediatric Disease status to RP L102 for the treatment of Fanconi ´s anaemia [3].
Jun 18EMA classifies RP L102 as an Advanced Therapy Medicinal Product [3].


An autologous gene therapy where stem cells are taken from the patient and modified genetically ex vivo using a lentiviral vector to express a functional copy of the FANC-A gene, which is translated to the FANC-A protein. Given as a single dose.
A rare genetic multisystem disorder characterized by progressive pancytopenia with bone marrow failure, variable congenital malformations and predisposition to develop hematological or solid tumors. The expected prevalence at birth is at least 1 per 160,000 [1].
Fanconi anaemia (FA)
Intravenous infusion

Trial or other data

May 22Positive clinical data announced from pivotal PII trial which met primary endpoints. In 5 of 9 pts MMC-resistance increased to 51%-94% at 18 to 21 months, up from 21%-42% at 12 to 18 months accompanied by concomitant genetic markings and haematologic stabilisation. A 6th pt displayed evidence of progressively increasing genetic correction as evidenced by peripheral VCN and 2 additional pts are currently 12 months post-treatment whilst 1 pt had progressive bone marrow failure and required allogeneic transplant. Three of 12 pts have not yet reached the 12-month time point. Safety of RP-L102 was favorable with no signs of dysplasia, clonal dominance or oncogenic integrations. There was a grade 2 transient infusion-related reaction, which resolved. [8]
Apr 21Rocket summarises data presented at the ASH Annual Meeting in Oct 20 from seven of the nine patients treated (out of twelve patients enrolled) in both the U.S. PI and global PII studies of RP-L102. Seven patients had follow-up data of at least two-months and three of the seven patients had been followed for twelve-months or longer. As patients are treated with gene therapy product without the use of a conditioning regimen, the data indicated that RP-L102 was generally well-tolerated with no significant safety issues reported with infusion or post-treatment. One drug related serious adverse event of Grade 2 transient infusion-related reaction was observed. In five out of the seven patients for whom there was follow-up data, evidence of preliminary engraftment was observed, with bone marrow vector copy numbers (VCNs) from 0.16 to 0.22 (long-term follow-up only) and peripheral VCNs ranging from 0.01 (2-month follow-up) to 0.11 (long-term follow-up). Further, two of the three patients with greater than 12-months follow-up showed evidence of increasing engraftment, mitomycin-C (MMC) resistance and stable blood counts, which suggests a halt in the progression of bone marrow failure. The third patient with greater than 12-month follow-up contracted Influenza B nine months post-treatment resulting in progressive BM failure, for which, such patient received a successful bone marrow transplant at 18 months post-treatment. Longer-term follow up on these patients is expected Q2 2021 [6].
Nov 20Both PI trial (NCT03814408) and PI/II FANCOLEN-I trials are no longer recruiting; PII (NCT04248439) trial is recruiting [2].
Jul 20PII trial to assess the therapeutic efficacy of RP-L102 for patients with FA-A starts (NCT04248439). 5 children aged 1 year and older and adults will be recruited in the US. Primary outcome is phenotypic correction of bone marrow colony forming units after infusion of RP-L102 at 3 years; collection of these data is due to complete Jun 22 [2].
May 20Rocket announces data from a PI/II study (NCT03157804). Patients followed for a year or more after treatment with RP-L102 Process A continue to demonstrate durable engraftment and hematologic correction, without the use of pre-treatment conditioning regimens. All six patients who received minimally adequate drug product and were followed for more than one year display sustained and progressive engraftment. Haemoglobin levels have normalized to baseline in two patients treated. Rocket says this gives them confidence to transition to the improved Process B drug product, but also supports the potential of gene therapy in the absence of any conditioning regimen as a definitive haematologic treatment for FA. The ability to treat patients without the side effects associated with allogeneic transplant or the use of genotoxic conditioning, and to restore blood cell counts is a major milestone [5].
Nov 19PII registration-enabling study using Process B to evaluate the efficacy of RP-L102 starts (NCT04069533). 5 patients aged 1 to 17 years will be recruited in Spain. Primary outcome is phenotypic correction of bone marrow colony forming units after infusion of RP-L102; collection of these data is due to complete Jan 23 [2].
Jan 19PI trial to assess the therapeutic safety and preliminary efficacy of RP L102 with FA subtype A (FA-A) starts (NCT03814408; RP-L102-0418). The open-label trial is enrolling 2 patients aged 1 to 12 years in the US. will include a safety evaluation and preliminary assessment of the efficacy of hematopoietic gene therapy consisting of autologous CD34+ enriched cells transduced with a lentiviral vector carrying the FANCA gene in subjects with FA-A. CD34+ cells will be transduced ex vivo with the therapeutic lentiviral vector and infused following transduction, without any prior conditioning. After transduction, product quality control evaluations will be carried out in aliquots of the transduced population. Investigational product will be infused via intravenous infusion with no upper or lower limit; a dose of ≥5 x 105 CD34+ cells/kg body weight will be considered optimal. The active agent is a self-inactivating lentiviral vector carrying the therapeutic FANCA gene and the therapeutic product is subject´s autologous HSCs that have been transduced with the lentiviral vector. The vector contains the functional FANCA gene. Primary outcome is safety; collection of these data is due to complete Dec 20 [2].
Jan 16PI/II FANCOLEN-I trial of RP L102 to evaluate the safety and efficacy of RP-L102 gene therapy procedure with an orphan drug consisting of a lentiviral vector carrying the FANCA gene for patients with Fanconi anemia of Subtype A (FA-A) starts (NCT03157804; 2011-006100-12). CD34 + cells will be taken and transduced ex vivo with lentiviral vector carrying the gene FANCA, PGK-FANCA-Wpre. It will enrol 9 patients aged 1 to 12 years in Spain. Primary outcomes are safety and proportion of patients with at least 0.1 copy of the therapeutic vector per nucleated bone marrow or peripheral blood cells three years after infusion; collection of these data is due to complete Dec 20 [2].