Voxelotor

Novo Nordisk is known for making therapies for some of the world’s most prevalent conditions, but it’s also working on candidates for some of the least common. Though the company’s rare disease unit is active in hemophilia and endocrine disorders, one of its most interesting up-and-coming assets is intended for sickle cell disease. Ludovic Helfgott, Novo’s head of rare disease, told Endpoints News on Thursday that data from a late-stage trial of etavopivat in sickle cell should come next year. That readout will indicate if the drug can overcome the worrying precedents set by other sickle cell treatments and whether Novo’s $1.1 billion buyout of Forma , which developed etavopivat, was in fact a good move. The company is targeting a 50% cut in the rate of vaso-occlusive crises (VOCs) in etavopivat’s Phase 3 study, according to Helfgott. This is roughly in line with the 46% cut in VOCs that the pyruvate kinase activator demonstrated in Phase 2 . In a Dec. 10 note, Leerink analysts said etavopivat’s VOC reduction in the mid-stage trial narrowly met the bar for clinical meaningfulness. However, they also wrote that etavopivat may have an important place in the sickle cell market given the high unmet need after Pfizer pulled its sickle cell drug Oxbryta worldwide last year over safety concerns. Plus, Europe and the UK a year ago rescinded approval of Novartis’ sickle cell therapy Adakveo, citing a no longer favorable “benefit-risk balance.” Helfgott is clear that Oxbryta’s withdrawal has no read-through to etavopivat. “We have a complete different molecule,” he said. “From a safety perspective, what Pfizer decided to do has no implication on what we do. It’s a completely different mode of action.” From a public health perspective, however, he noted that “it’s never a good thing when a medicine is withdrawn.” Patients have fewer treatment options, and Helfgott also said that there has been “a bit of mistrust in medicines” among sickle cell patients in recent years “and having a medicine withdrawn, unfortunately, doesn’t really help that.” Even with the much-anticipated arrival of sickle cell gene therapies, uptake has been slow. Vertex Pharmaceuticals’ Casgevy is slowly taking off , though it’s not a viable therapy for most sickle cell patients, who live in developing countries and have no way of paying roughly $2 million for treatment. Then there’s bluebird bio’s Lyfgenia, which stalled commercially. The biotech was sold to investors last month for just $29 million upfront. If etavopivat’s Phase 3 data are good enough for approval, it could have a pretty clear run at the sickle cell market, particularly if it shows a benefit on a secondary endpoint. The trial aims to demonstrate that the therapy can reduce the organ damage from sickle cells’ inability to deliver oxygen to patient tissues. “If you can show that you can preserve the organs better, then you have something which, for me, is really clinically relevant,” Helfgott said. Novo is investing heavily in its rare disease unit, which Helfgott refers to as “a company within a company.” It brings in around 8% to 10% of Novo’s annual revenue but accounts for more than 14% of the pharma’s R&D spend. The products it is developing are at least partly a hedge against hard times ahead. “The bigger the obesity [market], the bigger the diabetes [market], the bigger you need to compensate when loss of exclusivity will happen,” Helfgott said. “It’s really a strategic play for Novo Nordisk to have the rare disease segment alongside the more prevalent diseases.”

Pfizer is ending the development and commercialization of its hemophilia B gene therapy Beqvez, the company confirmed in an emailed statement to Endpoints News . The company cited “limited interest patients and their doctors have demonstrated in hemophilia gene therapies to date.” It marks an abrupt end for the gene therapy for the rare, inherited bleeding disorder. Pfizer gained FDA approval for the one-time treatment last April, and the New York pharma giant rolled it out at a price of $3.5 million. The drugmaker didn’t disclose any updates on the gene therapy during its recent earnings. A decade ago, it had licensed Beqvez from Spark Therapeutics, which is now owned by Roche. Kim Phelan, CEO of the Coalition for Hemophilia B, said the nonprofit was “disappointed to hear of this discontinuation,” but that they “respect Pfizer’s decision as they evaluate their portfolio and future direction.” “Importantly, we remain hopeful and reassured that individuals with hemophilia B still have access to an approved gene therapy option,” Phelan said in a statement, referring to CSL Behring’s Hemgenix. CSL has struggled to gain traction for the multimillion-dollar treatment. The pullback casts a new pall over the blood disorder landscape. Two months ago, Pfizer axed its partnership on another gene therapy, a hemophilia A treatment from Sangamo Therapeutics that cleared a Phase 3 last summer. The drugmaker also pulled another blood disorder drug , the sickle cell treatment Oxbryta, last fall after saying the “totality of clinical data” showed the overall benefit of the drug “no longer outweighs the risk.” “We will communicate to those Beqvez patients who are in the qualification process and their providers who have initiated the qualification process and follow their desired pathway through our decision,” the Pfizer spokesperson said in an email. “For any patient who has been treated with Beqvez in any clinical trial, Pfizer remains committed to supporting the clinical trial sites and patients with regard to clinical trial follow-up and patient and trial support.” Pfizer markets another drug for hemophilia A and B. In October, the FDA greenlit the company’s once-weekly injectable, branded as Hympavzi .