GBT Bucks Gene Therapy Trend With Sanofi Sickle Cell Deal

Building on Oxbryta, which is already approved in the US for the rare blood disorder, Global Blood Therapeutics has licensed two sickle cell disease programs from Sanofi.

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300,000 people around the world are born with SCD each year

While a number of companies are pursuing genetic approaches to cure sickle cell disease, Global Blood Therapeutics, Inc., which has one of the two drugs approved for the hereditary blood disorder in Oxbryta, is focusing on improving treatment and has bagged two early-stage programs from Sanofi.

The US biotech has entered into an agreement with the French drugmaker to exclusively in-license worldwide rights to the SCD programs, one that pursues a novel anti-sickling mechanism and another "that leverages a new approach to reduce inflammation and oxidative stress." These mechanisms are "distinct and potentially complementary to that of Oxbryta (voxelotor) tablets," GBT said.

Oxbryta, a hemoglobin S polymerization inhibitor, was approved in the US in November 2019, just over a week after Novartis AG's biologic Adakveo (crizanlizumab) was also given the green light by the FDA for SCD. The two approvals were seen as game-changing, given the failure of numerous compounds in the space.  (Also see "Global Blood Therapeutics' Oxbryta Approved Broadly For Sickle Cell Disease " - Scrip, 25 Nov, 2019.) (Also see "FDA Approval For Novartis’s Sickle Cell Treatment Adakveo" - Scrip, 18 Nov, 2019.)

The programs have been developed at Sanofi’s rare blood disorders unit Bioverativ Inc. and supplement "GBT’s existing pipeline and support the company’s strategy to address SCD from multiple approaches," the California-based firm stated. Under the terms of the agreement, GBT will conduct all R&D, regulatory and commercialization activities worldwide and while the upfront payment is small – just $2.25m – Sanofi is entitled to receive about $351m in development, regulatory and commercial milestones, plus single-digit tiered royalties.

Jung Choi, chief business and strategy officer at GBT, said, "We envision a future in which SCD is a well-managed condition with the potential for a functional cure in the form of patient-friendly oral therapies." She added that the company was "advancing our robust internal research programs with disease-modifying potential while continually exploring partnership opportunities across a variety of mechanisms. These novel discovery programs represent promising approaches."

The take-up of Oxbryta, which had a net price of around $8,000 per month when approved by the FDA, has not been stellar. Fourth-quarter 2020 sales reached $41.3m, boosted by 950 new prescriptions of Oxbryta during the period despite a dramatic increase in COVID-19 cases that hit patient interactions; GBT believes that when the pandemic subsides, the number of new prescriptions will surpass pre-COVID-19 levels.

On the research front, GBT also plans to initiate two major trials of inclacumab, a P-selectin antagonist licensed from Roche Holding AG in 2018, to begin before the end of the first half of 2021. One study will focus on the reduction in vaso-occlusive crises (VOCs) and the second is looking at reducing 90-day hospital readmission following an initial VOC hospitalization. (Also see "GBT Picks Up Inclacumab From Roche's Bargain Bin" - Scrip, 24 Aug, 2018.)

Analysts at Wedbush Securities issued a note saying that they view the Sanofi deal as positive "as it supports the company’s strategy to address SCD via multiple novel mechanisms." The broker also noted that GBT has initiated a Phase I study on the safety and tolerability of GBT601, a next-generation hemoglobin S polymerization inhibitor, in healthy volunteers and plans to report proof-of-concept data by year-end.

Gene Therapies For SCD On The Way

However, one errant mutation causes the disease so SCD has become a prime target for gene therapy. Over 300,000 people around the world are born with SCD each year and patients of African descent and sub-Saharan Africa make up roughly 80% of cases.

Leading the way is bluebird bio's LentiGlobin but last month the company announced that it had temporarily suspended its SCD Phase I/II and Phase III studies of the ex vivo gene therapy after receiving reports that one patient developed acute myeloid leukemia (AML) and another developed myelodysplastic syndrome (MDS). However, bluebird said 10 March that the AML case was likely not related to the therapy itself, although the MDS case remains under review.  (Also see "Bluebird Bio Gets Relief, But Gene Therapy Hurdles Remain" - Scrip, 10 Mar, 2021.) (Also see "Bluebird Sickle Cell Gene Therapy Hangs In Balance" - Scrip, 16 Feb, 2021.) 

CRISPR Therapeutics AG and Vertex Pharmaceuticals Incorporated are also making good progress with their CRISPR/Cas9 gene therapy CTX001. Data from two ongoing Phase I/II open-label trials presented at last year's American Society of Hematology meeting which showed that all three SCD patients dosed with CTX001 remained VOC-free with follow-up ranging from three to 15 months and had hemoglobin levels in the normal to near normal range. (Also see "New CRISPR Therapeutics/Vertex Data Dangle The Hope Of Cure For SCD and TDT" - Scrip, 7 Dec, 2020.)

Novartis also recently partnered with the Gates Foundation to develop a low-cost accessible in vivo gene therapy for SCD that could potentially be administered once directly to the patient without the need to modify cells in a lab. Speaking to Scrip last month, Lutz Hegemann, head of corporate affairs and global health for Novartis, said that with Adakveo, plus its Africa SCD program, which was first launched in Ghana in 2019 and aims to reach nine other African countries by 2022, "we are trying to keep patients in reasonable health until they can ultimately benefit from curative therapy."

Despite the GBT deal, Sanofi has not abandoned SCD. A Phase I/II study has been initiated evaluating BIVV003, a gene-edited cell therapy candidate developed with Sangamo Therapeutics, Inc..