As Biosimilars Close In, Innovator Biologic Developers Forge New Strategies

As brand-name biologics that have achieved strong sales begin to age, and as biosimilar developers grow closer to gaining approval for and launching their products, innovator biologic developers are taking on new strategies to defend their profits and market share.

One such developer is Regeneron, which this month released positive phase 3 study data from its PANORAMA trial of its blockbuster brand-name aflibercept, Eylea, in patients with moderate to severe nonproliferative diabetic retinopathy (NPDR).

The study found that, in patients with NPDR who did not receive the study drug, 15% had a 2-step improvement or greater on the Diabetic Retinopathy Severity Scale (DRSS) compared with 65% and 80% of patients who received aflibercept every 16 weeks or every 8 weeks, respectively.

Patients who received aflibercept also had fewer vision-threatening events than those in the control group, with 10% and 11% of patients treated with the study drug every 16 and 8 weeks, respectively, having such an event versus 41% of patients in the control group.

Regeneron reports that it has submitted a supplemental Biologics License Application (BLA) for the drug in diabetic retinopathy, and it expects an FDA decision in May 2019.

Meanwhile, Alteogen, Coherus, and Momenta are all developing biosimilars of aflibercept.

A drug maker taking a different approach to mitigating the effects of biosimilar competition, Alexion also had positive phase 3 data to report for an innovator drug in recent days. Alexion’s C5 complement inhibitor, ravulizumab, recently approved under the brand name Ultomiris, is Alexion’s follow-up to eculizumab, sold as Soliris and targeted by multiple biosimilar developers.

The data from the ULTOMIRIS aHUS-311 study conducted in 56 adults report on ravulizumab used to treat complement inhibitor—naïve patients with atypical hemolytic uremic syndrome (aHUS), an ultra-rare disease characterized by inflammation and the formation of blood clots in small blood vessels throughout the body, leading to irreversible organ damage and premature death.

The drug, says Alexion, met its primary endpoint; in the first 26 weeks of treatment, 53.6% of patients (95% CI, 39.6%-67.5%) demonstrated a complete thrombotic microangiopathy response, defined by hematologic normalization and improved kidney function for at least 28 consecutive days.

Alexion noted in its fourth-quarter 2018 earnings call that it is moving forward with regulatory filings for a ravulizumab indication in aHUS, and it continues to seek to transition patients already taking eculizumab onto the newer ravulizumab. Alexion’s chief commercial officer, Bryan Goff, said that the company is hoping for a 70% conversion from eculizumab to ravulizumab within the next 2 years ahead of biosimilar market entry.

A third strategy is one piloted by Roche and its Genentech division, which recently announced submission of a supplemental BLA for its ado-trastuzumab emtansine, an antibody-drug conjugate sold as Kadcyla, for the treatment of patients with HER2-positive early breast cancer with residual disease after neoadjuvant treatment. The drug, a so-called “biobetter” of the originator trastuzumab, Herceptin, combines trastuzumab with the chemotherapy agent DM1.

The supplemental BLA for ado-trastuzumab emtansine relies on data from the phase 3 KATHERINE study that showed that the conjugate significantly reduced the risk of invasive breast cancer recurrence or death from any cause by 50% compared to the originator trastuzumab alone. At 3 years, 88.3% of patients treated with the conjugate did not have a recurrence, compared with 77.0% of patients treated with trastuzumab.

An expanded label for the biobetter could help Roche and Genentech to defend against competition for trastuzumab as more biosimilars gain approval in Europe and the United States.