8-9 - News

In December 2021, the US Food and Drug Administration (FDA) approved Bristol Myers Squibb’s (BMS) arthritis drug, Orencia (abatacept), the first therapy designed to prevent aGvHD.

Haematopoietic stem cell transplantation (HSCT) is an effective treatment and cure for haematological malignancies and other non-malignant haematological diseases.
However, up to 70% of patients that receive stem cell transplants, especially those who receive them from an unrelated donor, are impacted by acute graft-versus-host disease (aGvHD), where the transplanted donor T cells attack the recipient’s healthy tissue and organs.

BMS’ drug, Orencia, can now be given, in combination with a calcineurin inhibitor and methotrexate, to adults and children aged two years and older who are undergoing haematopoietic stem cell transplantation from a matched or 1 allele-mismatched unrelated donor.

“Acute graft-versus-host disease can affect different parts of the body and become a serious post-transplant complication,” said Dr Richard Pazdur, director of the FDA’s Oncology Center of Excellence. “By potentially preventing the disease, more patients may successfully undergo bone marrow or stem cell transplantation with fewer complications.”

The FDA’s review of Orencia was part of Project Orbis, which “enabled concurrent and/or shared FDA review with the health authorities in Canada, Switzerland and as a pilot in Israel”, said BMS, although it stressed that Orencia was not yet approved for this indication in those countries.

After being granted a Priority Review in July 2021, AstraZeneca and Amgen’s Tezspire (tezepelumab-ekko) has been approved by the US Food and Drug Administration (FDA) as an add-on maintenance treatment for adults and children aged 12 years and over with severe asthma.

Tezspire is a first-in-class biologic for severe asthma that acts at the top of the inflammatory cascade by targeting thymic stromal lymphopoietin (TSLP), an epithelial cytokine. It is the first and only biologic to consistently and significantly reduce asthma exacerbations across a broad population of severe asthma patients, said the companies.

Around 10% of people living with the condition are considered to have severe asthma, a complex and often uncontrolled form. Severe asthma is debilitating, with patients experiencing frequent exacerbations, significant limitations on lung function and a reduced quality of life, as well as an increased risk of mortality.

“Due to the complex and heterogeneous nature of severe asthma and despite recent advances, many patients continue to experience frequent exacerbations, an increased risk of hospitalisation and a significantly reduced quality of life,” said Professor Andrew Menzies-Gow, director of the lung division, Royal Brompton Hospital, London and principal investigator of the NAVIGATOR trial.

Results from the pivotal NAVIGATOR trial saw Tezspire demonstrate superiority across every primary and key secondary endpoint in patients with severe asthma, compared to placebo, when added to standard therapy.

The US Food and Drug Administration (FDA) has approved Amgen’s Otezla in milder stages of plaque psoriasis, making it the first and only oral treatment for adults with plaque psoriasis across all severities, including mild, moderate and severe.

Globally, 125 million people have psoriasis, a serious, chronic inflammatory disease that causes raised, red, scaly patches to appear on the skin. Plaque psoriasis is the most common form of the disease, affecting about 80% of patients.

“Plaque psoriasis can place a significant burden on the lives of patients, regardless of the severity of skin involvement,” said Dr David Reese, head of R&D at Amgen. “A substantial unmet need remains for mild to moderate plaque psoriasis patients for whom topical therapies may not be sufficient, especially for those with difficult-to-treat areas, like the scalp.

“With this expanded indication for Otezla, patients across all levels of disease severity now have an oral, systemic option that has already been used by more than 650,000 people worldwide and has no lab monitoring requirement,” Reese added.

The FDA approval is based on findings from the phase 3 ADVANCE trial, in which five times as many adults with mild to moderate plaque psoriasis who were receiving Otezla achieved the primary endpoint compared to placebo.

Following approval by the US Food and Drug Administration (FDA) in the late summer, AstraZeneca’s Saphnelo (anifrolumab) is set to be available to lupus patients in Europe following a positive opinion from the Committee for Medicinal Products for Human Use (CHMP).

The committee has recommended the monoclonal antibody to the European Medicines Agency (EMA) as an add-on treatment for moderate-to-severe systemic lupus erythematosus (SLE).

The positive recommendation from the CHMP was based on three trials including the pivotal TULIP (Treatment of Uncontrolled Lupus via the Interferon Pathway) phase 3 programme. In TULIP-2, Saphnelo demonstrated superiority across multiple efficacy endpoints versus placebo.

The most common form of lupus, SLE affects approximately 250,000 people in Europe, especially women who are diagnosed between the ages of 15 and 45.

SLE is a complex autoimmune condition and can affect any organ and if unmonitored can lead to long-term organ damage and poor health-related quality of life.

Saphnelo is available as an infusion but AstraZeneca is running a phase 3 trial to assess the antibody as a subcutaneous injection. If approved by the EMA, Saphnelo would be the first new treatment for SLE in Europe in more than a decade.

Biogen has obtained a licence from Ionis Pharmaceuticals to develop and commercialise BIIB115/ION306, an investigational antisense oligonucleotide (ASO). The licence is worldwide and exclusive and may include royalty payments.

Currently in development, BIIB115 may have the potential to help address additional unmet needs of patients with spinal muscular atrophy (SMA) and may also offer patients the option of extended dosing intervals.

SMA is a rare, genetic, neuromuscular disease that is caused by a deficiency in the production of survival motor neuron (SMN) protein and can affect individuals of all ages, with varying levels of disease severity.

The deficiency is due to a damaged or missing SMN1 gene and BIIB115 is designed to target a root cause of SMA by increasing the production of functional SMN protein.

SMA is characterised by the loss of motor neurons in the spinal cord and lower brain stem, resulting in severe and progressive muscular atrophy. Left untreated, the survival rate of children with the most severe form of SMA does not usually extend to beyond two years of age.

As well as the one-time $60 million payment to Ionis, made in the fourth quarter of 2021, future payments from Biogen may include potential post-licensing development, regulatory and commercial milestone payments and royalties on annual worldwide net sales.

The US Food and Drug Administration (FDA) issued Takeda with a Complete Response Letter stating the rejection of its oral suspension of the corticosteroid budesonide for the treatment of eosinophilic oesophagitis (EoE).

Around one in 2,000 people in the US are known to have been affected by eosinophilic oesophagitis – a rare, chronic inflammatory disease of the oesophagus. Symptoms of EoE include vomiting, heartburn and difficulty swallowing.

A complex mix of genetics, environmental factors and immune system dysfunction is believed to be responsible and can – in more severe cases – lead to a narrowing of the oesophagus, causing food to become lodged.

Takeda hoped that an oral suspension of the drug, designed specifically to treat the localised inflammation caused by EoE, would become the first FDA-approved treatment for the chronic condition. The company even announced its intended brand name for the treatment, Eohilia, yet these hopes now appeared to have been dashed by the FDA.
The rejection by the FDA potentially clears the way for Sanofi’s Dupixent, which received breakthrough therapy designation in EoE in September 2020.

In October 2021, Sanofi announced results of a second phase 3 trial for Dupixent in
EoE that showed improvements in swallowing and reduced inflammation. Dupixent
is a monoclonal antibody that is believed to target the cause of the inflammation seen in EoE.

FDA approves first prophylactic drug against graft-versus-host disease

AstraZeneca’s Tezspire approved in US for severe asthma

Amgen’s Otezla granted FDA approval for all patients with plaque psoriasis

European approval of AstraZeneca’s Saphnelo expected following CHMP recommendation

Biogen and Ionis
in deal to develop ASO for spinal muscular atrophy