AbbVie's $10B cancer drug Rova-T panned at ASCO

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CHICAGO--AbbVie ($ABBV) got a chance on Sunday to start explaining just why it was inspired to pay a whopping $5.8 billion upfront--with $4 billion reserved for milestones--for Stemcentrx and its overnight cancer drug sensation Rova-T. But their first slice of data proved to be a major disappointment, sending shares down by 5% in Monday morning trading.

The results are still preliminary, but investigators spotlighted results at the ASCO Annual Meeting 2016, which showed that 11 out of 60 (18%) evaluable patients getting Rova-T (rovalpituzumab tesirine) experienced tumor shrinkage, and 41 (68%) achieved a clinical benefit, clearing the minimum bar for stable disease. 

The treatment is an antibody-drug conjugate. Researchers at the biotech unicorn developed an antibody that targets the protein DLL3 which is frequently found on the surface of SCLC tumor cells. And they linked it to a DNA-damaging agent that could be dropped on target, hitting a pathway that plays a big role in maintaining stem cells. 

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Significantly, it was those patients with the highest levels of DLL3 in tumors that demonstrated the best response--with 10 of 26 patients (39%) responding to the therapy. The median overall survival rate was 5.8 months with 32% of the patients alive after a year of treatment. And half of the 12 third-line patients experienced tumor shrinkage.

If the data hold up in pivotal studies, Rova-T could become the first targeted drug ever approved for small cell lung cancer, one of the most lethal cancers to beat. But AbbVie’s decision to pay a blockbuster price for Rova-T triggered some head-shaking among industry observers looking over the results. Matthew Herper at Forbes took a look at the data--including a 5.8-month median survival rate against a 4.7-month historical average--and concluded that “many on Wall Street are likely to find that 1-month survival benefit disappointing.”

“If the deal hadn't happened, would we be saying 'Wow, these are $5.8B (possibly $10B) results!'” tweeted biotech investor Brad Loncar.  “No.”

Geoff Meacham at Barclays also wasn't impressed, especially if you compare Rova-T with a rival combo from Bristol-Myers Squibb ($BMY). 

"Investors are likely to be underwhelmed by the profile thus far for Rova-T following the presentation of the Phase 1 data, which showed good ORRs but only a modest incremental median overall survival (OS) benefit," he offered in a note. "We believe that the recent resilience in ABBV shares following the institution of the ’135 patent IPR and ASR program was largely supported by optimism about Rova-T. While both of the SCLC data sets are early and have wide confidence intervals, we think investors will likely see Bristol's Opdivo/Yervoy combo as the initial winner in SCLC even though the panel noted a place for both approaches." 

Stemcentrx used a 7-year wind-up in stealth mode to quietly explore the role of DLL3 under the eye of Scott Dylla, the chief scientific officer and company co-founder, with CEO Brian Slingerland. Now, though, the team will be working in the public spotlight with close attention from Wall Street, which will want to size up the drug’s market potential, along with the rest of the biotech’s pipeline. And they plan to move fast.

Slingerland tells me that the first pivotal study in third-line SCLC will enroll about 150 patients, and they’ll look for data that can be filed in a BLA next year. The Stemcentrx team, which remains in charge of the work, will also shoot for a breakthrough drug designation with priority review status.

Gary Gordon, the vice president for oncology at AbbVie, also isn’t fazed by the initial backlash over the preliminary data this weekend. 

“I think it’s pretty exciting,” he tells me, with clear evidence of a “dramatic” tumor response among some very sick patients with advanced cases, some of of whom have been on the drug for awhile. The frontline study, says Gordon, will start in the next 6 to 7 months and the team is also lining up an immunotherapy for a combination approach to cancer.

David Carbone, a professor at Ohio State who’s been involved in the ongoing research work, explains that the DLL3 molecule is a Notch ligand found in two thirds of all small cell lung cancer cases. When overexpressed, it activates ASCL1, which is a main driver of small cell lung cancer.

Grappling onto DLL3 allows precise delivery of pyrrolobenzodiazepine dimer, a potent agent which damages DNA, directly into the cancer cells, he adds. 

There have been few advances for SCLC over the years, says Carbone, who still relies on the same chemo used when he started out treating patients 25 years ago. Now, immunotherapies and Rova-T are finally promising to change those standards. 

“If it pans out,” he adds, “it could become a standard treatment for the disease.”

For AbbVie, Rova-T almost immediately became a top exhibit in its case that the company has the pipeline to deliver enough goods to one day replace Humira after it loses patent protection. Following the Pharmacyclics buyout, Rova-T offered fresh evidence of the company’s willingness to spend big to become a major player in oncology.

Founders Fund, Fidelity, Capital Group, Sequoia Capital and Artis Ventures attracted a blaze of attention after providing a $250 million round to the low-profile Stemcentrx that valued the company at a whopping $5 billion. 

“Although these results are preliminary, rovalpituzumab tesirine seems to be the first targeted therapy to show efficacy in small cell lung cancer, and we may have identified DLL3 as the first predictive biomarker in this disease,’ noted Charles Rudin, the lead researcher and chief of Thoracic Oncology Service at Memorial Sloan Kettering Cancer Center in New York.

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