Bluebird’s investors relieved by sickle cell abstract data

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Rarely have investors awaited the contents of a single conference abstract more eagerly. Initial results on the first patient treated with Bluebird Bio’s LentiGlobin BB-305 gene therapy in sickle cell disease, published today ahead of a presentation at the European Hematology Association conference on June 13, appeared to surpass the already high expectations. Bluebird’s shares are up 5% in early trading.

The abstract is the second update from the ongoing HDC205 trial of LentiGlobin BB-305 in seven patients with beta-thalassaemia and sickle cell. When Bluebird revealed data from this study on four patients with beta-thalassaemia at ASH last year its stock doubled overnight. It has since doubled again, and with today’s rise the company now has a market value approaching $6bn. 

The key disclosure was that the patient's proportion of haemoglobin A produced by the transfected gene (as determined by the proportion carrying the marker T87Q) had reached 24% at 4.5 months' follow-up, up from 9.6% at three months. It looks like the patient is well on course to reach the targeted 30% threshold thought to represent a functional cure.

The 30% threshold is derived from the level of non-sickling foetal haemoglobin (Hb F) in asymptomatic sickle cell patients. Indeed, it seems a reasonable bet that Bluebird will be able to report in the actual EHA presentation in June that this level has been breached, since the abstract would have been filed based on data available in February.

Bluebird also noted that the patient, a 12-year old boy who was treated last October, did not engraft until after month one, so his level of HbAT87Q at months three and 4.5 were really reflective of the levels at two and 3.5 months after engraftment. Furthermore, at 4.5 months' follow-up, his total anti-sickling haemoglobin (Hb AT87Q + Hb F) had reached 31.6%. 

The patient had been receiving chronic transfusions on entry to the trial and began being weaned off them after day 37, receiving his last transfusion on day 88. In addition, he has not been re-hospitalised for a sickle cell-related event since being treated with the gene therapy.

Sickle cell disease is thought to have a prevalent population of around 90,000 in the US and 125,000 in the EU. Assuming LentiGlobin does indeed represent a functional cure, analysts have generally assumed that it could command a price of at least $1m per patient, perhaps payable over three years. Depending on assumptions of penetration this would give rise to sales of $3-4bn in sickle cell at peak, sometime in the mid 2020s. A further $1bn plus is generally forecast for beta-thalassemia.

Bluebird is one of a handful of companies with developments in sickle cell, which historically has seen very little pharmaceutical innovation. Interest in the condition as a commercial opportunity is increasing and could gain further impetus if phase III data from one of the pioneers in the sickle cell space, Mast Therapeutics, are positive.

Mast’s Epic study examines whether vepoloxamer can reduce the duration of vaso-occlusive crises that patients with sickle cell suffer periodically, and should render results in early 2016. Pfizer has just started a phase III study of rivipansel for the treatment of vaso-occlusive crises, with results expected in 2018.

Early approval in beta thalassemia

Meanwhile, Bluebird reported earlier this week that it had reached agreement with regulators on a development pathway for BB-305 that could result in accelerated approval in beta thalassaemia. This plan envisages seeking conditional approval in the EU on the basis of the two studies already under way and in the US with two additional, 15-patient, studies.

Whether the investors are so accommodating for sickle cell disease remains to be seen.

Sickle cell anaemia therapies in pipeline    
Product Company Pharmacology class Study NCT ID  Primary completion
Phase III vepoloxamer Mast Therapeutics Poloxamer EPIC, 388 patients, vs placebo NCT01737814 Dec 2015
Rivipansel Pfizer Pan selectin antagonist 350 patients vs placebo NCT02187003 Jul 2018
Eliquis Bristol-Myers Squibb Factor Xa inhibitor 60 patients vs placebo NCT02179177 Aug 2015
Effient Lilly/Daiichi Sankyo Platelet ADP antagonist 240 paediatrics vs placebo NCT01794000 Jul 2015
Phase II Aes-103 Baxter  Direct anti-sickling agent 50 patients vs placebo NCT01987908 Jun 2015
SelG1 Selexys Anti-P-selectin MAb SUSTAIN, 174 pts +/- hydroxyurea vs placebo NCT01895361 Aug 2015
LentiGlobin bluebird bio Haemoglobin gene therapy 7 patients (including Beta thal) NCT02151526 Dec 2017
NiCord Gamida Cell Hematopoietic stem cell therapy 10 patients NCT01590628 Aug 2014
Zolinza Merck & Co HDAC inhibitor 5 patients NCT01000155 Oct 2014
Brilinta AstraZeneca Platelet ADP receptor antagonist HESTIA 1, 39 patients, vs placebo NCT02214121 Sep 2015
T-Cell Depleted Allogeneic Stem Cell Miltenyi Biotec CD34+ cell therapy HaploSCD, 35 patients NCT01461837 Apr 2017
Sanguinate  Prolong PEGylated carboxyhemoglobin bovine 24 patients, vs placebo NCT02411708 Apr 2016

To contact the writer of this story email Robin Davison in London at news@epvantage.com or follow @RobinDavison2 on Twitter

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