EMA's CHMP Recommends Approval of Ten Innovative Therapies Including Monthly HIV Regimen and RNAi Treatments from Alnylam and Novartis

Recently, at its October meeting, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) announced support for the marketing authorization applications of 10 drugs in the European Union. Among these are innovative therapies not yet approved by the U.S. Food and Drug Administration (FDA), such as the once-monthly long-acting HIV therapy jointly developed by Janssen, a subsidiary of Johnson & Johnson, and ViiV Healthcare; Alnylam Pharmaceuticals’ RNA interference (RNAi) therapy Oxlumo (lumasiran); and Novartis’ RNAi therapy Leqvio (inclisiran). Below, we take a closer look at these innovative therapies expected to receive approval in the EU this year.

Long-Acting Therapy Reducing Annual Treatment Days for HIV Patients from 365 to 12 or 6 Days

The CHMP announced its support for the approval of a combination therapy consisting of cabotegravir (injectable/tablet) developed by ViiV Healthcare and rilpivirine (injectable/tablet) developed by Janssen, a subsidiary of Johnson & Johnson, for the treatment of adults with HIV-1 infection who have previously received antiretroviral therapy and achieved virologic suppression.

The use of antiretroviral “cocktail” therapy to treat HIV infection is one of the most significant advances in medicine over the past 25 years. Currently, there are multiple single-tablet regimen combination therapies that effectively control HIV-1 viral replication; as long as patients adhere to daily medication, their life expectancy is not significantly different from that of the general population. However, if patients are unable to take their medication daily for any reason, the virus may not only rebound but also pose an increased risk of developing drug resistance. Until curative therapies become available, daily medication remains a burden for many people living with HIV.

This long-acting intramuscular therapy consists of rilpivirine and cabotegravir. Rilpivirine is an oral non-nucleoside reverse transcriptase inhibitor. Cabotegravir is an integrase inhibitor that functions by preventing the integration of viral DNA into the genome of human immune cells. This integration step is essential for HIV replication and is a major contributor to chronic infection.

The application for this new drug is based on the pivotal Phase 3 clinical trials ATLAS, FLAIR, and ATLAS-2M. The ATLAS and FLAIR studies included more than 1,100 participants from 16 countries. These studies demonstrated that during the 48-week study period, once-monthly intramuscular injections of cabotegravir and rilpivirine in the buttocks were non-inferior to continued once-daily oral antiretroviral therapy in maintaining viral suppression. In the ATLAS and FLAIR studies, approximately 9 out of 10 patients preferred switching to long-acting cabotegravir and rilpivirine therapy compared with their previous daily oral regimens.

Data from the pivotal ATLAS-2M trial demonstrated that cabotegravir and rilpivirine administered every two months met non-inferiority criteria for antiviral activity and safety compared with monthly dosing.

This innovative combination therapy was approved for marketing by Health Canada earlier this year, and ViiV Healthcare has resubmitted its new drug application to the U.S. FDA in July this year.

RNAi Therapy That Lowers “Bad” Cholesterol with Just Two Injections per Year

The CHMP announced its support for the marketing authorization of Leqvio (inclisiran), an RNAi therapy acquired by Novartis through its acquisition of The Medicines Company, for the treatment of primary hypercholesterolemia or mixed dyslipidemia.

Inclisiran is a subcutaneously administered RNA interference (RNAi) therapy that targets mRNA encoding PCSK9. It has demonstrated consistent lipid-lowering efficacy in three Phase 3 clinical trials. In the ORION-10 and ORION-11 trials, which enrolled patients at risk for atherosclerotic cardiovascular disease (ASCVD), 90% of patients achieved LDL-C levels below the normal threshold of 70 mg/dL, and 87% of patients experienced a reduction in LDL-C levels of more than 50%. This suggests that Inclisiran holds promise for playing a significant role in reducing the risk of major adverse cardiovascular events (MACE) in these patients. The detailed results of these three trials have been published in the New England Journal of Medicine.

Image source: Novartis official website

The New Drug Application for Inclisiran is currently under review by the U.S. FDA.

Alnylam Pharmaceuticals’ RNAi Therapy for Primary Hyperoxaluria Type 1

CHMP Announces Support for Marketing Authorization of Alnylam’s Oxlumo (lumasiran) for the Treatment of Primary Hyperoxaluria Type 1 (PH1). The press release stated that this will be the first approved therapy for PH1 in the European Union.

Primary Hyperoxaluria Type 1 (PH1) is a rare genetic liver disease. Patients with PH1 have mutations in the gene encoding human alanine-glyoxylate aminotransferase (AGT), leading to AGT deficiency. This results in excessive oxalate production in the body, which accumulates in the kidneys and cannot be excreted promptly. In severe cases of PH1, oxalate deposits occur in multiple parts of the body, damaging the kidneys and related organs, often necessitating liver and kidney transplantation.

Image source: Alnylam Pharmaceuticals official website

Lumasiran is a subcutaneously administered RNAi therapeutic that targets the mRNA of the HAO1 gene, which encodes glycolate oxidase (GO) in the liver. It reduces hepatic oxalate production by lowering GO expression. This RNAi therapeutic utilizes Alnylam Pharmaceuticals’ Enhanced Stabilization Chemistry (ESC)-GalNAc delivery platform. This platform not only enhances the stability of the RNAi therapeutic but also facilitates its targeted delivery to the liver. Its New Drug Application submitted to the U.S. FDA has been granted Priority Review, with approval expected later this year.

Alnylam Pharmaceuticals announced the key Phase 3 clinical trial data for lumasiran this June. In the ILLUMINATE-A clinical trial, 39 patients with PH1 received treatment with either lumasiran or a placebo. During the 3-6 months following treatment, the average urinary oxalate levels in the lumasiran group decreased by 65.4% compared to baseline and by an average of 53.5% compared to the placebo group. In the lumasiran group, more than half of the patients had their urinary oxalate levels return to normal, and 84% of patients had levels close to normal, whereas this figure was 0% in the placebo group.

This month, the company announced that lumasiran also demonstrated favorable efficacy and safety in infants and young children aged 3 to 72 months.

In addition to the aforementioned therapies, drugs supported by the CHMP for approval and market launch also include:

Libmeldy, a gene therapy developed by Orchard Therapeutics, uses a lentiviral vector to introduce the ARSA transgene encoding arylsulfatase A into patients’ autologous CD34-positive hematopoietic stem and progenitor cells for the treatment of metachromatic leukodystrophy (MLD), a rare genetic disorder caused by ARSA gene mutations. This innovative gene therapy has not yet received FDA approval.

Tecartus (KTE-X19), a CD19-targeted CAR-T therapy developed by Kite Pharma, a Gilead Sciences company, received accelerated FDA approval in July this year for the treatment of patients with relapsed or refractory mantle cell lymphoma.

Zogenix’s Fintepla (fenfluramine) for the treatment of seizures associated with Dravet syndrome.

Aimmune's Palforzia for the treatment of peanut allergy.

AstraZeneca maintains Trixeo Aerosphere for the maintenance treatment of COPD.

Mylan’s generic lenalidomide for the treatment of multiple myeloma and follicular lymphoma.

Note: This article is intended to introduce medical and health research and does not constitute a recommendation for treatment plans. For guidance on treatment options, please consult a qualified healthcare provider at a reputable hospital.

Reference: [1] Meeting highlights from the Committee for Medicinal Products for Human Use (CHMP) 12-15 October 2020. Retrieved October 16, 2020, from https://www.ema.europa.eu/en/news/meeting-highlights-committee-medicinal-products-human-use-chmp-12-15-october-2020

[2] Janssen Receives Positive CHMP Opinion for Long-Acting Regimen for the Treatment of HIV. Retrieved October 16, 2020, from https://www.businesswire.com/news/home/20201016005352/en

[3] ViiV Healthcare receives positive CHMP opinion for long-acting regimen for the treatment of HIV. Retrieved October 16, 2020, from https://www.businesswire.com/news/home/20201016005380/en

[4] Orchard Therapeutics Receives Positive CHMP Opinion for Libmeldy™ for the Treatment of Early-Onset Metachromatic Leukodystrophy (MLD). https://www.globenewswire.com/news-release/2020/10/16/2109748/0/en/Orchard-Therapeutics-Receives-Positive-CHMP-Opinion-for-Libmeldy-for-the-Treatment-of-Early-Onset-Metachromatic-Leukodystrophy-MLD.html

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