Less than two weeks after giving the go-ahead to Novartis AG for Adakveo (crizanlizumab) to reduce the frequency of vaso-occlusive crises (VOCs) in adult and pediatric patients ages 16 and older with sickle cell disease (SCD), the FDA cleared – well ahead of its Feb. 26, 2020, PDUFA date – Oxbryta (voxelotor), from Global Blood Therapeutics Inc. (GBT), for SCD in adults and pediatric patients ages 12 and up. 

Oxbryta, given fast-track and orphan status, is an inhibitor of deoxygenated sickle hemoglobin polymerization, the main abnormality in SCD. The drug from South San Francisco-based GBT makes cells less likely to bind together and form the distinctive sickle shape, leading to low hemoglobin levels due to red blood cell destruction.  

U.S. regulators based Oxbryta’s accelerated approval on results from a trial that enrolled 274 patients. Ninety received 1,500 mg of oral Oxbryta, 92 were given 900 mg, and 92 more took a placebo. Effectiveness was based on an increase in hemoglobin response rate in patients who received 1,500 mg, which was 51.1% for those patients compared to 6.5% in the placebo group. Common side effects for patients on drug were headache, diarrhea, abdominal pain, nausea, fatigue, rash and pyrexia. 

In a Nov. 8 report, Wainwright analyst Debjit Chattopadhyay anticipated the approvals of Basel, Switzerland-based Novartis’ P-selectin-binding player as well as the GBT compound. “Given our confidence on a first-pass accelerated approval for voxelotor and the likely approval of crizanlizumab, the SCD community would have access to two therapeutic alternatives addressing a non-overlapping patient population initially,” he wrote. “Importantly, voxelotor is potentially endowed with long-term disease-modifying credentials that would be evaluated in postmarketing commitments through a range of company and investigator-sponsored studies [that] were outlined during the company investor event” in October. Given Oxbryta’s mechanism of action, “we would envision improvements in rates of stroke, pulmonary hypertension, renal failure, priapism, and leg ulcers, which in totality could shift the mortality curve in the SCD community over the long run,” he said.

As a daily therapy, Oxbryta likely will be incorporated into routine practice in concert with hydroxyurea. Selectins like crizanlizumab, on the other hand, requiring I.V. infusion, “remain more suited for patients with history of VOC events or in the acute setting to decrease the number of days requiring hospitalization,” in Chattopadhyay’s view. 

With the approval, Chattopadhyay weighed in again, remarking that the FDA “does buy into the hemolysis story after all.” He cited the drug’s list price of $10,417 per month, or about $125,000 annually, with an estimated net price of about $8,000 per month, or $96,000 annually. “Clearly, the incessant focus on VOCs was not aligned with the thought process at the agency, and as outlined repeatedly in our prior notes, the October 2017 FDA/American Society of Hematology [ASH] workshop served as the de facto advisory committee meeting” and “exquisitely outlined the evolution from VOC management to the prevention of end organ damage as the overarching goal.” 

J.P. Morgan analyst Cory Kasimov called the price “materially higher than expected” and he liked the “relatively clean label. We have adjusted our model accordingly and have raised our December 2020 price target to $80 (vs. $75 previously). Bigger picture, today’s approval/label positions the company well for 2020 (and beyond) and serves to further underscore GBTs strategic value.”

Shares (NASDAQ:GBT) closed Tuesday at $62.99. 

Oppenheimer’s Mark Breidenbach, with an outperform rating on the shares, set the price target at $100. The lack of restrictions in Oxbryta’s label with regard to genotype or baseline hemoglobin represents “a best-case scenario,” he said in a report. “Based on our discussions with key opinion leaders and GBT’s ongoing education initiatives, we believe Oxbryta will be widely utilized,” he added. 

The company expects to have Oxbryta in the channel via specialty pharmacy in two weeks. That will happen first through medical exceptions, with formulary access expected to take three to six months. GBT will have a fully branded booth at the upcoming ASH meeting in Orlando, Fla., with additional secondary analyses, to boost physician education. Officials also intend to talk with the FDA about options for expanding the label to younger children and will be discussing the compound with European regulators soon. 

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