Etavopivat

To date, Novo Nordisk’s focus in rare disease has hinged on blood and endocrine disorders, with its efforts yielding a number of approved treatments. While Novo Nordisk has been operating in rare disease for some 45 years, the field has often taken a back seat to the Danish drugmaker’s bread-and-butter business developing treatments for diabetes and other common chronic diseases.Still, Novo is steadfast in its goal to eventually become a leader in the space, the company’s EVP of rare disease, Ludovic Helfgott, said in an interview with Fierce Pharma following the company’s 2025 international press briefing on Thursday. Overall, the near-term success of those ambitions will come down to a handful of new drug launches and a sickle cell disease (SCD) candidate that recently entered phase 3 testing.Plus, Novo will continue to seek external opportunities to refine its rare disease pedigree, Helfgott said.From 'back burner' to full throttle Novo Nordisk's rare disease ambitions first began to shift when Lars Fruergaard Jørgensen donned the mantle of CEO in 2017.“One of the intuitions that Lars had when he joined the CEO chair was to say, we have here something which is an uncut gem—something which is a rough diamond that we might want to polish, because at some point it might be very, very helpful,” Helfgott said of the company’s rare disease unit.When Helfgott joined Novo from AstraZeneca in 2019, he immediately set out on a mission to create “a biotech within Novo Nordisk," he explained.“There was a long endgame in being a leader in rare disease,” Helfgott added.While Novo has subsequently made strides building out capabilities in early research, development and its supply chain to embrace that newfound purpose—including recent designs on a $1.2 billion rare disease production plant in Denmark—there is still much work to be done, Helfgott said.“When I joined the company back in 2019, the R&D efforts [in rare disease] honestly had been a bit put on the back burner, and we had to reengage with research,” he explained. Over the past few years, Novo has relied on its dealmaking prowess to wade deeper into the space, but in order to be a discerning purchaser and partner, the company had to bolster its own R&D abilities too, Helfgott said.“The problem is that if you don’t have your internal quality research and development, you don’t do good [business development] because you can’t assess quality molecules, and you’re not really a credible partner,” he explained.In an example of how Novo’s rare disease outfit has since grown, Helfgott noted that the company’s early research team for the business has swelled from just eight people to around 90 since the executive’s arrival.Those efforts to bulk up in rare disease R&D, both internally and externally, have since led to some major rare disease deals for Novo in recent years, including the company’s $1.1 billion buyout of sickle cell disease-focused Forma Therapeutics in 2022 and its acquisition of 2seventy bio’s hemophilia A program in 2024.Building a path to the top To date, Novo’s focus in rare disease has hinged on blood and endocrine disorders, with those efforts yielding a number of approved hemophilia A and B treatments like Esperoct, NovoEight and Rebinyn, as well as drugs for growth hormone-related disorders such as Norditropin.More recently, Novo in December won a hard-fought FDA approval for its once-daily hemophilia injection Alhemo. The tissue factor pathway inhibitor (TFPI) antagonist, which is injected under the skin, is specifically approved to prevent or curb the frequency of bleeding episodes in patients 12 and older who have hemophilia A or B with certain factor inhibitors.Factor inhibitors are a complication of the rare bleeding disorder that can prevent factor replacement treatments—a well-established class of drugs for hemophilia—from working properly.Given Alhemo’s unique mode of action, much of Novo’s launch focus in the U.S. currently revolves around investments in medical education, Helfgott said. The company is also playing up the drug’s convenient subcutaneous delivery via prefilled syringe, which is a first in the hemophilia B space, where many medicines are infused, the executive pointed out.Outside the U.S., Alhemo has also won green lights in Australia, Japan and Switzerland and the European Union.Beyond hemophilia, the next frontier for Novo’s blood disorder focus is SCD, where the company recently advanced the asset etavopivat it picked up from Forma Therapeutics into phase 3. Patients with SCD are living with “two evils,” to hear Helfgott tell it. They’re forced to endure painful vaso-occlusive crises (VOCs), in which blood vessels are blocked and deprive tissues of oxygen, as well as the subsequent organ damage that results from those repeated VOCs, he explained.Novo hopes that etavopivat can tackle both issues at once, which even newer SCD meds have failed to achieve, Helfgott said.Back in December, Novo posted phase 2 data on etavopivat showing the highest studied dose (400 mg) nearly halved patients’ annualized VOC rates at the study’s 52-week mark compared with placebo. Etavopivat also appeared to delay the onset of patients’ first VOC, according to data presented at last year’s meeting of the American Society of Hematology (ASH).What's next for Novo in rare diseases As Novo looks to carve out a leadership position in the field, the company’s rare disease unit will retain its focus on blood and growth disorders, Helfgott said.“It’s our core, and we will continue to develop this both internally and externally,” he explained.As for how Novo aims to dig deeper into those disciplines, the company has grown “increasingly interested” in what it calls the “hemato-renal area,” which refers to the confluence between rare blood and kidney disorders, Helfgott said.To that end, Novo in late 2023 won an FDA nod for its ribonucleic acid interference (RNAi) drug Rivfloza to treat the rare disease primary hyperoxaluria type 1 (PH1). The disease is characterized by an overproduction of oxalate, which causes kidney stones to form and lead to progressive kidney damage.Rivfloza kicked off its U.S. launch “a few months ago,” with a European rollout soon to follow, Helfgott said. Meanwhile, M&A and other business development deals aren’t off the table as Novo looks to expand in blood, hemato-renal and endocrine disorders, the executive pointed out.External dealmaking could also deepen Novo’s access to new and promising modalities, as was the case with the $600 million collaboration agreement the company inked with NanoVation Therapeutics in September.Under that accord, Novo has secured a license to use NanoVation’s long-circulating lipid nanoparticle technology to develop two base-editing therapies in rare genetic diseases. The deal also covers up to five more targets in rare and cardiometabolic conditions. 

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.”