bluebird bio Defies RAC Panel's Recommendation, Will Proceed With Two Planned Trials

Published: Jun 11, 2015

Bluebird Defies RAC Panel's Recommendation, Will Proceed With Two Planned Trials
June 10, 2015
By Riley McDermid, BioSpace.com Breaking News Sr. Editor

A panel of scientists convened by the National Institutes of Health (NIH) Recombinant DNA Advisory Committee has recommended that freshly IPO’d biotech darling bluebird bio delay its two upcoming trials of beta thalassemia for one to two years in order to gather more safety information—and Bluebird has decided to ignore that advice.

The RAC committee was most concerned that bluebird bio halt testing its LentiGlobin BB305 gene therapy on children until more adults have been studied for side effects and safety concerns.

Nonetheless, Bluebird said late Tuesday it would continue laying the groundwork for its planned clinical trials HGB-207 and HGB-208, both of which will test LentiGlobin BB305 further, in attempt to have enough trial data to receive regulatory approval for the therapy from the U.S and European regulators. Because the RAC’s recommendation is nonbinding, Bluebird has chosen to steer its own course, said execs.

“We appreciate the recommendations from the RAC members regarding the HGB-208 pediatric study protocol,” said David Davidson, chief medical officer in Bluebird.

“We will take the RAC feedback on the timing of initiating HGB-208 under advisement as we advance the clinical development of our LentiGlobin BB305 product candidate for patients with beta-thalassemia major,” he said. “The HGB-207 trial protocol did not require further review by the RAC, and we will continue to work closely with the regulatory authorities and our clinical study sites to pursue appropriate accelerated regulatory approval pathways in the U.S. and the EU.”

Bluebird CEO Nick Leschly went one step further, telling closely watched biotech columnist Adam Feuerstein at The Street that the company disagrees with the RAC’s conclusion..

"We respect RAC and the process. RAC took a reasonable position when it comes to dealing with kids,” said Leschly. “We disagree and believe the decision [to proceed with a gene therapy pediatric study] should be placed in the hands of the institutional review boards, the physicians of patients and their families," said Leschly.

On Feb. 2, 2015, Bluebird announced that the U.S. Food and Drug Administration (FDA) had granted LentiGlobin BB305 Breakthrough Therapy designation, which is used to expedite the development and review of a potential drug candidate that is expected to be used to treat a serious or life-threatening diseases.

In the case of LentiGlobin BB305, initial data last fall from an ongoing Phase I/II Northstar (HGB-204) and HGB-205 studies looked at eight patients with beta-thalassemia that were treated with LentiGlobin. In the first four patients, treatment resulted in sufficient hemoglobin production to decrease the need for transfusion support among the patients.

That news sent shares of the company up 70 percent the day it was announced, as the market looked eagerly for signs that Bluebird’s LentiGlobin BB305 could be a panacea for blood diseases. In mid-May, Bluebird announced one of the patients treated in the earlier study has not had to seek hospitalization for his sickle cell since and has even started producing anti-sickling properties.

“The early data included in our abstract provide further validation for our approach and important insights into the safety and mechanism of action of LentiGlobin in both beta-thalassemia and sickle cell disease,” said Davidson, chief medical officer for Bluebird.

“As noted in the abstract, we are pleased to report that the two patients with beta-thalassemia major, on whom we first reported last year at EHA, remained transfusion independent at 14 and 11 months post-transplant,” he said. “In addition, it is very encouraging that the patient with sickle cell disease is increasing production of HbAT87Q, which has anti-sickling properties, and has not had a post-treatment hospitalization for a sickle cell disease-related event. At EHA we will present further follow up data on all three subjects.”

That news had both analysts and Wall Street investors cheering, because it shows LentiGlobin is on track.

“Our recent deep dive on LentiGlobin combined with this update keep us confident that BLUE is on the cusp of a dramatic breakthrough for many sickle cell disease patients and we await further updates,” wrote Joshua Schimmer, a biotech analyst for Piper Jaffray, in a note to investors.

Bluebird’s LentiGlobin BB305 extracts blood stem cells and then infuses them with a working version of the malfunctioning gene that had caused the disease. People with the disease must undergo monthly blood transfusions in order to survive—but if Bluebird’s therapy continues to be successful, they may now be freed from that burden.

The number of people affected is not huge, but is certainly significant: Around 40,000 babies world-wide and between 1,000 and 3,000 in the U.S. are born with the condition each year.

The new therapy is so effective, Wall Street is champing at the bit to see it be rushed into later-stage trials to bring it to market more quickly. Some analysts have long said Bluebird has a “robust” proof of concept for the therapy so far, said Schimmer.

“The abstract notes the peripheral blood T87Q vector copy number is an impressive 2.4. This should be a good marker for what's happening in the bone marrow, meaning that a majority of cells have a copy of the corrected gene,” he wrote in his note. “This also means that BLUE's busulfan myeloablation regimen was effective in establishing chimerism with the LentiGlobin cells. And this also means that as the patient continues to be weaned from transfusions, the corrected cells should be easily able to ramp up production and eliminate sickling and its consequences.”

The results of this data, though hardly extensive, are apparently promising enough for the FDA and the European Medicines Agency (EMA) to consider conditional approval for use of the drug.

When Will Pfizer's Breakup Happen?
Speculation that the revamping of Pfizer Inc. ’s internal business structure could happen as soon as this year has biotech wondering just when this Big Pharma company could see changes.

Last week an analyst with J.P. Morgan said he thinks there will be a much faster timeline than most of Wall Street had predicted for Pfizer’s stated mission to refocus its efforts on new medicines.

Pfizer initially announced in 2012 that it would be shedding units that were non-essential to that goal. It then promptly sold its nutrition silo to Nestle for $11.85 billion, which was rapidly accompanied by a public spin-off of its animal health business for $2.2 billion.

“While a Pfizer break-up would likely be a 2017 event, we see potential catalysts in 2015-2016," said Chris Schott, an analyst at J.P. Morgan. "Three years of audited financial statements (2014-2016) are required before any part of Pfizer can be spun off, and we also see 2017 as an attractive time for action as investors see Pfizer’s innovative pipeline clearly contributing to growth and the established business having transitioned to a more stable profile."

BioSpace wants to know what you think: Will Pfizer be a changed company by the end of 2015?

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