Bluebird and Roche drugs gain Breakthrough status

Excitement about Bluebird Bio has just risen even higher after the FDA granted one of its lead products breakthrough therapy status.

The special fast-track treatment is for LentiGlobin BB305, a potentially groundbreaking treatment of transfusion-dependent patients with the rare blood disorder beta-thalassemia major.

Analysts at JP Morgan said in a recent analyst note that the Cambridge, Massachusetts company is one of the more "potentially transformative and disruptive companies we have come across in a long time," and now the FDA breakthrough status has backed up this view.

JP Morgan forecasts that LentiGlobin could earn around $1 billion in peak sales, but stress that the company must first prove the safety and efficacy of its new gene therapy platforms.

The company's platform is lentiviral-based gene therapy and gene editing capabilities, which could be used to treat a broad range of severe genetic diseases and to develop T cell-based immunotherapies.

Patients with beta thalassaemia major develop life-threatening anaemia from the age of around four to six months, and must undergo monthly blood transfusions as well as additional treatment to prevent complications, such as chelation drugs to remove excess iron from the body.

LentiGlobin BB305 aims to treat beta-thalassemia major and severe sickle cell disease by inserting a functional human beta-globin gene into the patient's own hematopoietic stem cells in a procedure performed outside the body. These modified cells are then returned to the patient through an autologous stem cell transplantation.

Early results from LentiGlobin BB305 have been very promising indeed: a single treatment of the gene therapy corrected the main genetic defect which causes the condition.

Results from the firm's Northstar study presented at the American Society of Haematology (ASH) meeting in December showed that four patients treated with LentiGlobin BB305 have not needed any blood transfusions for up to 12 months.

The firm has another lead clinical programne, its Lenti-D product is currently in a Phase 2/3 study, called the Starbeam Study, for the treatment of childhood cerebral adrenoleukodystrophy.

Bluebird is also one of the leaders in another exciting emerging platform, CAR T cancer immunotherapy, in which it is collaborating with Celgene.

Roche's MPDL3280A in non-small cell lung cancer

Meanwhile Roche has gained a second breakthrough status for its investigational cancer immunotherapy MPDL3280A (anti-PDL1).

The designation was granted for the treatment of people with PD-L1 (Programmed Death-Ligand 1) positive non-small cell lung cancer (NSCLC) whose disease has progressed during or after platinum-based chemotherapy (and an appropriate targeted therapy for those with an EGFR mutation-positive or ALK-positive tumour).

This helps Roche (led by its Genentech division) keep up with its rivals in the field, with Merck's Keytruda having been granted breakthrough status in NSCLC in November, and BMS's Opdivo on a 'fast track' designation since 2013.

Opdivo and Keytruda are neck-and-neck in their race to be the first to gain approval in NSCLC, with both drugs likely to get the green light in 2015.

BMS saw its Checkmate-017 trial stopped early in January after it easily achieved its primary endpoint, helping patients live longer than those on docetaxel treatment, a first in the PD-1/PD-L1 field.

Meanwhile Merck has said it would file its drug in mid-2015, setting it up a close race with its rival.

Tim Anderson, analyst at Bernstein predicted last month that Opdivo would be the likely market leader. He forecasts the BMS drug will earn around $4.5 billion by 2020, with Keytruda earning a little less at $3.8 billion, Opdivo having the edge in his opinion because of its broader development programme.

Roche's drug has a slightly different mechanism to the two frontrunners: it targets the PD-L1 ligand on the cancer cell, rather than the corresponding PD-1 site on the T-cells. Roche hopes that this approach could have a number of advantages, including fewer toxic side effects – but will have to demonstrate clear advantages in order to leapfrog the leaders.

This is MPDL3280A's second breakthrough designation, having gained it first last year for metastatic bladder cancer. The firm says it will launch Phase 3 studies in further tumour types this year.

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