Regeneron, Sanofi Drug Holds Up in Eczema Study

Xconomy New York — 

Regeneron Pharmaceuticals made a big splash last year with a drug prospect it believes just might hit the root cause of several allergic diseases. Today, it’s backing up that thesis with some new data showing that the drug might have a place treating one of the world’s most common skin disorders.

Tarrytown, NY-based Regeneron (NASDAQ: REGN) and partner Sanofi today are releasing positive results from a mid-stage trial testing their antibody drug hopeful, dupilumab, in patients with moderate to severe forms of atopic dermatitis—a skin condition commonly called eczema, which is characterized by intensely itchy red, scaly skin lesions (results from some earlier trials are also being published today in the New England Journal of Medicine). The data continue to fuel support for dupilumab, which has already showed promise as a treatment for allergic asthma. The two companies expect to kick off late-stage studies in atopic dermatitis in the U.S. and Europe later this year, according to Gianluca Pirozzi, the global project head for dupilumab at Sanofi.

Dupilumab is designed to work by blocking the signaling of the cytokines interleukin 4 and interleukin 13. Cytokines are signaling molecules that aid cell to cell communication in immune responses and stimulate the movement of cells towards sites of inflammation, infection, and trauma. The big idea here is that IL-4 and IL-13 may be key drivers of, potentially, a variety of allergic diseases—like eczema, certain forms of asthma, and nasal polyposis—opening up what could be big returns for the two companies if the drug can continue to produce good results. Last year, Regeneron, which discovered dupliumab with its in-house antibody technology, supported that idea with a mid-stage study in allergic asthma—in the 104-patient study, the drug was able to largely keep patients’ asthma from worsening, while improving their lung function.

Now, dupilumab appears to have potential in another market—atopic dermatitis. Pirozzi says that about 1 to 3 percent of the worldwide population has the disease, and roughly a third of those people have the moderate to severe forms of it. Patients are initially typically prescribed a variety of topical corticosteroid creams or phototherapy to control their eczema. While those treatments can be effective for many people, about 15 to 20 percent of those with more severe forms of the disease don’t respond, according to Pirozzi. Those patients often have to turn to broad immunosuppressive treatments, such as cyclosporine—which can only be used for a short time because of safety risks (and when those drugs are removed, the lesions return). This is where Regeneron and Sanofi are hoping to position dupilumab.

“The advantage here is for the first time you have a drug that can not only effectively solve the disease, but also can be given for a sustained effect over time,” Pirozzi says.

It’s still early, but the two companies are taking a step towards proving that today. They enrolled 380 patients with eczema that couldn’t be controlled by topical treatments and gave them either weekly, bi-weekly, or monthly injections of dupilumab at a high (300 mg), medium (200 mg), or low (100 mg) dose, or a placebo, and tracked their results for 16 weeks. The study’s main goal was to significantly reduce patients’ symptoms, as measured by a mean change on what’s called the Eczema Area and Severity Index (EASI)—a clinically-validated, composite score used to measure the prevalence and severity of patients’ eczema lesions—compared to placebo. Investigators also looked at whether dupilumab could help wipe out the lesions altogether, and if it helped alleviate itching.

Regeneron and Sanofi are saying today that dupilumab hit all of its marks, with the higher doses scoring better than the lower ones. Patients on weekly 300 mg doses of dupilumab, for instance, saw their EASI scores drop by 74 percent over the course of treatment; those on the lowest 100 mg, monthly dose saw their scores drop by 45 percent. By comparison, scores for patients getting the placebo treatment dropped by an average of 18 percent.

The two companies are also saying that between 12 and 33 percent of the patients treated with dupilumab had their lesions either completely or almost completely cleared, as measured by an investigator’s global assessment (IGA) scale, compared to 2 percent of the patients in the placebo group (they didn’t specify any further). On average, those patients started the trial with a 3.5 on the scale, which essentially means they had moderate or severe eczema lesions, according to Pirozzi.

“That’s a pretty impressive result given that even cyclosporine in the short term barely reaches these levels,” he says.

Regeneron and Sanofi also reported that patients taking dupilumab had anywhere from a 16.5 percent to 47 percent reduction in their itching, compared to 5 percent on average in placebo.

There is, of course, still a long way to the finish line for Regeneron and Sanofi. The two have to recreate these results in bigger, longer late-stage studies (likely at least a year long with more than 1,000 patients combined), and see them hold up, and also make sure no big safety issues crop up along the way—like serious infusion site reactions, always a potential problem with injectable biologic drugs. While infusion reactions, along with colds, were some of the most common side effects seen so far, Pirozzi says the majority of the reactions have been mild to moderate and tend to go away after a few hours. None were severe.

“That’s something that we’ll certainly monitor very closely,” he says.

Pirozzi notes that the main goal of a Phase 3 study in Europe will be a mean change in EASI score while in the U.S., the primary endpoint will be a change in IGA. The secondary goal for both will be to reduce patients’ itching. Pirozzi is confident dupilumab will make it through intact.

“Honestly I think the only thing that could be a problem would be an unexpected safety issue coming up in the Phase 3 that we haven’t seen so far,” he says.

Dupilumab is one of several drugs that are part of Regeneron’s big partnership deal with Sanofi, which also includes two late-stage antibodies—cholesterol-lowering drug alirocumab, and rheumatoid arthritis prospect sarilumab—and a few other candidates in earlier testing. Regeneron gets $160 million in R&D funding per year through the collaboration and splits the profits from the drugs that come out of the deal with Sanofi 50/50 in the U.S., and on a sliding scale internationally.

Sanofi, meanwhile, has also been accumulating more and more shares in Regeneron over the years. Sanofi held about 16 percent of Regeneron in January; it now owns 22.5 percent of the stock, and is allowed to hold up to 30 percent. Sanofi has publicly shot down the prospect of a takeover several times, however.