The strategic agreement between Gsk (https://www.gsk.com/) and Orchard Therapeutics (http://orchard-tx.com/) includes approved and investigational rare disease gene therapies, that will be transferred to Orchard, while Gsk will become an investor in the company, receiving a 19.9% equity stake along with a seat on the board. UK-based Orchard Therapeutics is mainly focused on clinical and preclinical gene therapies for primary immune deficiencies and inherited metabolic disorders. The acquired portfolio includes Strimvelis, the first autologous ex vivo gene therapy for children with adenosine deaminase severe combined immunodeficiency (ADA-SCID), two late-stage clinical programmes for metachromatic leukodystrophy (MLD) and Wiskott Aldrich syndrome (WAS), and one clinical programme for beta thalassaemia.
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Subcutaneous therapy for chronic inflammatory demyelinating polyneuropathy
The European Commission has authorized the marketing of Hizentra (human normal immunoglobulin) as the first and only subcutaneous immunoglobulin (SCIg) for maintenance therapy in patients with chronic inflammatory demyelinating polyneuropathy (CIDP), after stabilization with immunoglobulin by intravenous (IVIg). The approval is based on data obtained from the phase III PATH study (Polyneuropathy And Treatment with Hizentra), the largest randomized placebo-controlled clinical trial in patients with CIDP. The results of the PATH study showed that, following the switch from intravenous to subcutaneous therapy, the rate of disease recurrence and exit from the study for any other reason was significantly lower among patients treated with subcutaneous (39% in the low dose therapy group of Hizentra [0.2 g / kg per week], 33% in the high dose therapy group [0.4 g / kg per week]) compared to the placebo group (63%).
Green light to gemtuzumab ozogamicin for acute myeloid leukemia
Gemtuzumab ozogamicin given in combination with daunorubicin and cytarabine, has been shown to prolong the life span of patients for up to 8 months before the cancer has returned to manifest. This is the motivation that led the European Commission to authorize the marketing of the drug for the treatment of acute myeloid leukemia (AML). This is the European opinion although some side effects of gemtuzumab ozogamicin may be serious. Gemtuzumab ozogamicin is authorized for patients over the age of 15 without prior treatment for AML. The drug is used in patients whose tumor cells have CD33 protein on the surface (as is the case for most patients with acute myeloid leukemia). It is not used instead for acute promyelocytic leukemia (APL). AML is “rare” and gemtuzumab ozogamicin has been defined as an “orphan medicinal product” on 18 October 2000. Gemtuzumab ozogamicin should be administered by intravenous infusion over 2 hours. The patient usually receives 3 infusions over a week along with daunorubicin and cytarabine. If the tumor responds to the initial treatment, the patient may receive an additional “consolidation” treatment to prevent the tumor from recurring. The active substance consists of two parts: a cytotoxic substance and a monoclonal antibody. As the antibody binds to CD33 on leukemic cells, the cells absorb the antibody and the cytotoxic substance attached to it. Once inside the cells, calicheamicin is released exerting its cytotoxic effect. A main study involving 271 patients with acute myeloid leukemia (AML) has shown that the addition of gemtuzumab ozogamicin to daunorubicin and to citarabine can prolong the life span of patients by approximately 8 months without the tumor returning. For patients who received gemtuzumab ozogamicin in combination with daunorubicin and cytarabine, an average of 17.3 months passed before treatment failed, before the tumor returned or before the patient died, compared to 9.5 months for patients who received a combination of only daunorubicin and cytarabine. The most common side effects with Mylotarg given in combination with daunorubicin and cytarabine are bleeding and serious infections.
Gene therapy for transfusion-dependent β-thalassemia
Recently have been published the results of two separate clinical trials of two years each showing the potential of gene therapy with LentiGlobina to eliminate or reduce chronic blood transfusions in patients with β-thalassemia transfusion-dependent. Both studies, Northstar (HGB-204), recently completed, and HGB-205, currently underway, are aimed at evaluating the safety and efficacy of a single-dose treatment of gene therapy based on LentiGlobin and whose interim results showed that most of the 22 patients in the two Phase 1/2 trials followed for two or more years remained transfusion-free. From a safety point of view, the collected profile was consistent with myeloablative conditioning and the busulfan chemotherapeutic agent. The recently completed Northstar study is a multicentre, open-dose, single-dose, non-randomized, Phase 1/2 study designed to assess the safety and efficacy of LentiGlobin in the treatment of patients with TDT. HGB-205 is an ongoing, single-dose, non-randomized, monocentric, single-dose, open-label, 1/2 study designed to assess the safety and efficacy of LentiGlobin in the treatment of patients with TDT and severe sickle cell anemia (SCD). The HGB-205 Phase 1/2 study is conducted in a single center in France. It is designed to evaluate the safety and efficacy of LentiGlobin in the treatment of subjects with TDT and SCD. Seven subjects were enrolled in the study. The intention of the manufacturer is to present, at the end of this year, an authorization request for the LentiGlobina for β-thalassemia transfusion-dependent to the EU.
Positive top-line data from the STORM study on selinexor in patients with refractory multiple myeloma
Karyopharm Therapeutics Inc., a clinical pharmaceutical company, reported first-line positive results from the STORM phase 2b study that evaluated the effect of selinexor in heavily pre-treated patients with refractory multiple myeloma. Regarding the primary objective of the STORM study, oral selinexor achieved a global response rate (ORR) of 25.4%, which included two complete (CR) and 29 partial (PR) responses or very good partial responses (VGPR) in these patients with refractory myeloma. The median duration of the response (DOR), a key secondary objective, was 4.4 months. All responses were confirmed by an independent review committee (IRC). Selinexor recently obtained the Fast-Track designation by the US Food and Drug Administration (FDA) for this indication.
Results of Phase 2a trial on safeproxalap for dry eye disease
Aldeyra Therapeutics presented the results of a randomized, double-blind clinical trial of phase 2a on patients with ocular dryness treated with reproxalap at the ARVO annual meeting. The main objective of the experimentation, that is to select a formulation for the Phase 2b clinical trial, was reached with the progress of reproxalap at 0.1%. Compared to baseline, patients with dry eye disease treated with 0.1% reproxalap showed a statistically significant improvement in tear volume (Schirmer test), as well as a statistically and clinically significant improvement in the overall 4-symptom score and in the ocular disability score. Fifty-one subjects with active dry eye disease were randomized to receive ocular reproxalap for topical use at 0.1%, reproxalap at 0.5% or reproxalap formulated with 0.5% lipids four times a day. The results indicated statistically significant changes in the SANDE score (Assessment symptom in the case of dry eye), the ocular discomfort score, the overall score of 4 symptoms, the tear volume (Schirmer test), the osmolarity and the coloration of the cornea (Lissamine Green). A modest dose-dependent response was observed and improvement in symptoms was observed within one week of therapy. In January 2018 Aldeyra announced the start of a Phase 2b clinical trial that will recruit 300 patients with active disease, randomized to receive 0.1% or 0.25% reproxalap. The results of the study should be announced in the second half of 2018.
Alnylam aligns with FDA for accelerated development of lumasiran in the treatment of primary type I hyperoxaluria
Alnylam Pharmaceuticals, an important company focused on RNAi therapies, announced that the Company has reached alignment with the US Food and Drug Administration (FDA) on a pivotal study project for lumasiran, an experimental RNAi for the treatment of primary hyperoxaluria type 1 (PH1). The Company and the FDA aligned on a primary endpoint for the registration study based on the reduction of six-month urinary oxalate, a biomarker directly related to the pathophysiology of PH1 and known to be well correlated with the progression of the disease. Furthermore, Alnylam and FDA have aligned themselves on a study size of about 25 patients with PH1. Based on discussions with the FDA, the Company is on track to begin the Phase 3 study in mid-2018, with plans to report topline results in 2019 and, if positive, to present an NDA at the beginning in 2020. Lumasiran was recently granted the designation of Breakthrough Therapy and Priority Medicines (PRIME) by the European Medicines Agency (EMA). Lumasiran offers hope to patients with PH1 who face health challenges. Alnylam’s alignment with the FDA key study project is an important step forward for patients suffering from this serious disease, as it recognizes the urgency of unmet need for effective treatment for PH1 and the potential for lumasiran to meet this necessity. The ongoing Phase I / IIb study is designed as a randomized, single-blind, placebo-controlled study. Patients with PH1, aged six or more, were enrolled.
New intermediate data in mycosis fungoides from a phase 1 study on cobomarsen
miRagen Therapeutics has announced new provisional data from its phase 1 clinical trial of cobomarsen in patients with mycosis fungoides (MF). The data were presented in May at “2015 … 2018 T-cell lymphomas: we are close to finalization”, meeting doctor held in Bologna. Additional data obtained on cobomarsen provide further evidence that microRNA therapies have the potential to improve quality of life for patients living with mycosis fungoides. Cobomarsen continues to be safe and generally well tolerated at all doses tested in the Phase 1 study, with more patients receiving more than one year of therapy without serious adverse events attributed to the drug. Furthermore, the improvement in skin disease observed in the study appears to be lasting and is accompanied by improvements in metrics that measure patients’ quality of life. These data support the company’s plans to initiate a phase 2 clinical trial in patients with CTCL in the second half of 2018. Intermediate results presented at the conference include safety observations from long-term administration to 18 patients. The highlights presented are:
- cobomarsen treatment has produced a lasting improvement in quality of life, as measured by the total Skindex-29 score.
- 13 out of 18 subjects showed improvement in the first 100 days with cobomarsen.
- Improvement and stabilization remain durable in four subjects up to one year after treatment and one subject was stable after more than 400 days of cobomarsen.
- Cobomarsen continued to be generally well tolerated at all assessed dose levels.
- More patients received more than one year of therapy (up to 39 grams of cumulative dose) without serious adverse events attributed to cobomarsen.
- 300 and 600 mg intravenous infusions have similar efficacy and tolerability, offering the highest response rate based on mSWAT skin scores.
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