The star of Abbvie Inc.'s multibillion-dollar acquisition of Stemcentrx Inc., rovalpituzumab tesirine (Rova-T), is officially dead after an interim analysis of the phase III Meru study found it failing to help people with advanced small-cell lung cancer (SCLC) live any longer than a placebo. Abbvie is terminating all further R&D of the disappointing asset.

The decision follows a $4.1 billion impairment charge it booked last year after another phase trial of Rova-T ended in a similar way. Company shares (NYSE:ABBV), appearing to have long ago adjusted to low expectations for the candidate, ended the day about where they began, at $66.22, down 28.2% year to date.

At the outset of the Meru trial, Abbvie had sought to enroll 740 people to test Rova-T as a maintenance therapy for advanced SCLC following first-line, platinum-based chemotherapy. But in a preplanned interim analysis, investigators found no survival benefit vs. placebo, leading an independent data monitoring committee to recommend stopping the trial.

High hopes

In April 2016, at the time of his team's $5.8 billion buyout of Stemcentrx, Abbvie CEO Richard Gonzalez hailed it as "a unique platform in solid tumor therapeutics," with Rova-T, an antibody-drug conjugate that had recently delivered "compelling" overall response rates and represented "a multibillion-dollar peak revenue opportunity." (See BioWorld, April 29, 2016.)

Excitement about the ADC turned on its ability to leverage the protein DLL3 – expressed in more than 80% of SCLC patient tumors but not healthy tissue – to target cancerous cells with a DNA-damaging pyrrolobenzodiazepine dimer toxin. But not only did the ADC fail to produce convincing benefits for DLL3-expressing SCLC patients in a third-line study, Trinity, it also failed to help those whose SCLC featured high expression of DLL3 in the second-line setting during another phase III study, Tahoe. (See BioWorld, March 23, 2018.)

The value of remaining assets from the Stemcentrx acquisition is unclear. Eight phase I programs originating at the company remain listed in Abbvie's publicly disclosed pipeline according to Cortellis, including SC-002, once positioned as a next-gen version of Rova-T with the potential to treat SCLC and neuroendocrine tumors. Other assets from the Stemcentrx cabinet include Pfizer Inc.-partnered PTK7 tyrosine kinase receptor modulator cofetuzumab pelidotin. Abbvie is also thought to be developing Stemcentrx-sourced ABBV-181, a humanized recombinant IgG1 mAb targeting PD-1, for the potential I.V. treatment of solid tumors.

Talent from Stemcentrx also continues to suffuse the North Chicago-based company, as evidenced by 23 former Stemcentrx employees with skills spanning nearly every aspect of clinical development listing their current employer as Abbvie on the profession networking site Linkedin.

But while Abbvie says its team will continue R&D for other therapies in the company's oncology portfolio, a representative declined an invitation for those familiar with the program to speak to lessons learned from the Rova-T adventure. Meanwhile, alongside '002 and '181, four additional programs for SCLC remain in its pipeline. Among them is the PARP-1 and -2 inhibitor veliparib, which has been tested in various combinations with some success. Phase II trials in the indication were the latest to wrap up.

The bigger picture

Regardless of how those programs turn out, individuals with advanced SCLC are in a much better position than they once were following the FDA's March approval of Genentech Inc.'s Tecentriq (atezolizumab), in combination with carboplatin and etoposide, for the first-line treatment of adult patients with extensive-stage SCLC. That development marked the first time in more than two decades a treatment has been shown to improve how long patients with the disease live, according to the National Cancer Institute. Periodic screenings of men and women at high risk of developing lung cancer because of their smoking history could also make a positive impact, an NCI-funded study found.

Despite the setback in SCLC, attentions to Abbvie's fortunes are likely to focus on other areas far beyond the indication, such as the company's proposed $63 billion acquisition of Allergan plc and its other ongoing efforts to reduce its dependence on Humira (adalimumab), including the sale of its psoriasis drug Skyrizi (risankizumab) and new rheumatoid arthritis therapy, Rinvoq (upadacitinib). With more than 300 trials currently underway and additional studies no doubt being planned, its team should have no trouble keeping busy despite having one less program to advance. (See BioWorld, June 26, 2019 and Aug. 19, 2019.)

No Comments