Type of information: Granting of a Fast Track status
Product name: lanadelumab (DX-2930 - SHP643)
Compound: monoclonal antibody inhibitor of plasma kallikrein - recombinant human IgG1 kappa light chain monoclonal antibody targeting plasma kallikrein
Therapeutic area: Rare diseases - Genetic diseases - Hematological diseases
- monoclonal antibody. DX-2930 is a novel, fully human monoclonal antibody inhibitor of plasma kallikrein (pKal) and is being developed by Dyax as a subcutaneous injection for the prevention of HAE attacks. Uncontrolled pKal activity leads to excessive generation of bradykinin, a vasodilator thought to be responsible for the localized swelling, inflammation and pain characteristically associated with HAE.
Company: Dyax (USA - MA), now Shire (UK - USA)
Disease: hereditary angioedema (HAE)
- • On February 27, 2018, Shire announced the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has granted an accelerated assessment for lanadelumab (SHP643). Shire is on track to submit its EU Marketing Authorization Application (MAA) in the coming weeks. Accelerated assessments by the CHMP of a marketing authorization filed under the centralized European procedure, reduces the amount of evaluation days required, from 210 to 150. The EMA will grant, upon request, accelerated assessment of an EU MAA if they deem the product to be of major interest for public health and therapeutic innovation.
- The clinical development program for Shire's investigational HAE treatment includes data from four clinical trials, including HELP™, the pivotal Phase 3 efficacy and safety study, along with interim data from its extension study. HELP, the largest prevention study in HAE conducted to date, enrolled a total of 125 patients aged 12 years and over with type I/II HAE. The HELP study demonstrated that subcutaneous administration of 300 mg lanadelumab once every two weeks resulted in an 87% reduction in the mean frequency of HAE attacks. In addition, an exploratory endpoint, which will require further confirmatory studies, showed that during the steady state stage of the trial (day 70-182) a 91% attack reduction was achieved with 8 out of 10 patients reaching an attack free state. In this study, no treatment-related serious adverse events or deaths were reported. The most common adverse event was injection site pain (29.3% placebo vs. 42.9% combined lanadelumab arms).
• On February 23, 2018, Shire announced the FDA accepted the Biologics License Application (BLA) and granted priority review for lanadelumab (SHP643). The BLA for Shire's investigational HAE treatment is supported by data from four clinical trials, including HELP™, the pivotal Phase 3 efficacy and safety study, along with interim data from its extension study. The FDA is expected to provide a decision on lanadelumab by August 26, 2018, based on the Prescription Drug User Fee Act V action date.
- • On September 1-3, 2015, the Committee for Orphan Medicinal Products (COMP) has recommended the granting of an orphan designation for recombinant human IgG1 kappa light chain monoclonal antibody targeting plasma kallikrein for treatment of hereditary angioedema.
- • On August 12, 2015, Dyax provided an update regarding its ongoing manufacturing initiatives for DX-2930. Dyax's manufacturing partner, Rentschler Biotechnologie GmbH (Rentschler), is responsible for providing cGMP (Current Good Manufacturing Practice) drug substance for certain future clinical trials and commercial supply. In preparation for commercial-scale production, Rentschler has commenced characterization and validation of the DX-2930 manufacturing processes. In addition, Rentschler will also support Dyax in the preparation of its submissions to regulatory authorities for marketing approval of the product. If DX-2930 is approved, Rentschler will be responsible for producing commercial supply. Dyax and Rentschler entered into a definitive manufacturing services agreement in 2014. Dyax looks forward to initiating the Phase 3 trial for DX-2930 in HAE patients during the latter part of this year.
- • On July 7, 2015, Dyax announced that the FDA granted Breakthrough Therapy designation for the investigation of DX-2930 for hereditary angioedema (HAE). Dyax is developing DX-2930, an investigational fully human monoclonal antibody inhibitor of plasma kallikrein (pKal), as a subcutaneous injection for prevention of HAE attacks. The designation is supported by the interim results of Dyax's Phase 1b clinical trial of DX-2930 in HAE patients. The Phase 1b study met all objectives assessing safety, tolerability and pharmacokinetics of multiple subcutaneous administrations of DX-2930. Additionally, in a pre-specified proof-of-concept efficacy analysis, DX-2930 demonstrated statistically significant reductions in attack rate compared to placebo.
- • On March 31, 2015, Dyax announced positive safety, pharmacokinetic, biomarker, and efficacy results from the Phase 1b clinical study of DX-2930. The company also announced receipt of Fast Track designation from the FDA for the investigation of DX-2930 for HAE.
- • On December 5, 2013, Dyax Corp. has announced that the FDA has granted orphan drug designation to its drug candidate DX-2930, its fully human monoclonal antibody inhibitor of plasma kallikrein, for use in the treatment of hereditary angioedema (HAE). Dyax is developing DX-2930 to be a long-acting, prophylactic agent that prevents HAE attacks. Development plans include a dosage formulation that will permit infrequent self-administration by small volume, subcutaneous injection. DX-2930 is currently being studied in a placebo-controlled, dose-escalation Phase 1 trial in normal individuals. Results from this study are expected in the first quarter of 2014.
Patents: * On September 15, 2014, Dyax announced that the U.S. Patent and Trademark Office (USPTO) has issued two new patents related to DX-2930. One patent, assigned U.S. Patent No. 8,816,055, contains claims covering the specific sequence of DX-2930, and the other, assigned U.S. Patent No. 8,822,653, contains claims covering monoclonal antibodies that bind to the active form of human plasma kallikrein and do not bind human pre-kallikrein. Both patents are expected to provide coverage for DX-2930 until at least 2032. Dyax is currently developing DX-2930 as a subcutaneous injection for the prevention of HAE attacks and expects to report data from a Phase 1b trial early in 2015.
Submission of marketing authorization application USA :
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
Favourable opinion UE:
Favourable opinion USA:
Orphan status USA: 2013-12-05
Orphan status UE: 2015-10-09
Pediatric exclusivit _USA:
Pediatric exclusivity UE: