Roche Considers Moving Two Drugs Into Phase III, Drops Early-Stage Alzheimer’s Compound In Strong 3rd Quarter
This article was originally published in The Pink Sheet Daily
Executive Summary
Roche is moving into Phase III with a Lucentis successor, lampalizumab, in ophthalmology, but has dropped development of a Phase I BACE inhibitor for Alzheimer’s disease, the company announced during a third-quarter earnings update, which highlighted pipeline tweaks amid comparatively strong product sales.
Roche Pharma AG highlighted some of its most promising treatments in oncology, immunology and ophthalmology when updating markets on its strong third-quarter sales performance on Oct. 17 and provided tidbits on some early assets outside its oncology expertise.
The world's largest maker of cancer drugs generated an 8% rise in third-quarter sales year-on-year, with sales of 34.9 billion CHF ($38.7 billion) in the first nine months of 2013. Growth was driven by its HER2 breast-cancer franchise (Herceptin, and two new compounds, Kadcyla and Perjeta); Avastin (bevacizumab ) and Actemra (tocilizumab) oncology products, with demand particularly strong in the U.S and China. The group now has 65 new molecular entities in its pipeline, with around two-thirds of its late-stage compounds being developed with a companion diagnostic.
Extolling its pipeline of follow-on cancer drugs – with Kadcyla (ado-trastuzumab emtansine) and fellow new medicine Perjeta (pertuzumab) continuing their strong launches (CHF156 million and CHF186 million, respectively from launch through Sept. 30, 2013) – Roche management also used the analysts’ conference call to again stress the advances being made outside the company’s oncology specialty field. Chief priorities outside of oncology include neuroscience, inflammation and ophthalmology (Also see "Roche Points To Pipeline Depth Beyond Oncology" - Pink Sheet, 15 Oct, 2013.) and (Also see "Roche’s Master Plan: Perjeta Gains Early Breast Cancer Approval, Late-Stage Kadcyla Data" - Pink Sheet, 30 Sep, 2013.).
Demand for eye drug Lucentis (ranibizumab) rose strongly in the latest quarter due to solid uptake in diabetic macular edema following FDA approval in this indication in August 2012 (Also see "Genentech Says Lucentis DME Product Will Ship Shortly" - Pink Sheet, 10 Aug, 2012.). Sales of Lucentis – the only anti-vascular endothelial growth factor (VEGF) medicine approved for DME in the U.S. – rose 13% year-on-year in the latest three months, while its share in wet age-related macular degeneration stayed stable after the FDA’s decision to update its label in early February 2013 to include a less frequent dosing regimen in wet AMD, Roche said.
Within ophthalmology, the company voiced particular excitement about lampalizumab, a human monoclonal antibody that inhibits complement factor D. Roche is considering designs for Phase III testing for the drug in geographic atrophy. “There is no effective treatment available to slow the progression of the disease today,” said Daniel O’Day, who heads Roche’s pharma division. “Geographic atrophy represents an approximate market opportunity to wet MD (macular degeneration), so the Lucentis marketplace. And we have the potential here I think to be the first compound to really show a difference in reducing the progression rate of that disease,” he said.
The drug is being tested with a biomarker that distinguishes patients who respond well to it. Phase II data showed a doubling of treatment effect in patient groups differentiated by the biomarker; specifics will be presented at the American Academy of Ophthalmology in November.
O’Day also underscored prospects for etrolizumab following “very encouraging Phase II results”. It has been moved into Phase III trials for ulcerative colitis and Crohn's disease, with recruitment of 3,000 patients planned to start in the first half of 2014. That late-stage program will evaluate the potential also for a companion diagnostic in that setting. The trial’s high number of patients is necessary “to make sure that you have an adequate safety database on these types of products in this area,” he said.
Roche is also on the verge of moving an ALK-inhibitor, alectinib, into pivotal Phase III trials for non-small cell lung cancer, based on promising Phase I data. The drug has received FDA breakthrough designation and is also pending approval in Japan.
Drops BACE Inhibitor, Anti-EGFL7 Oncology Drug
There was some negative news in that Roche has terminated testing in its BACE inhibitor after “safety signals” were seen in Phase I studies, but O’Day declined to give details. Bernstein analyst Tim Andersen said the move has implications for U.S.-based Merck & Co. Inc. and follows Eli Lilly & Co.’s decision in June 2013 to shut down a clinical trial of its BACE inhibitor in Alzheimer’s disease for similar reasons (Also see "Lilly Ends Trial Of BACE Inhibitor For Alzheimer’s, But Says Class-Wide Safety Effect Unlikely" - Pink Sheet, 14 Jun, 2013.).
This class of drugs appears to be vulnerable to off-target effects, but research so far has not produced evidence of a class-wide effect that would seem to doom all members, noted neuroscience consultant Harry Tracy, president of NI Research in Cardiff, CA. In this case, “the Phase I trial was just doing what it was supposed to do,” he said, adding that “It will be interesting to find out what went wrong for the Roche compound, but I don’t see anything here that says anything about competing programs other than mandating very close monitoring for a range of safety signals.
“Merck’s decision to enter (and thus far at least) continue Phase II/III for [it’s BACE inhibitor] MK-8931 can be assumed to be in the context of laser-like scrutiny,” he said, given that company’s propensity for being hyper-obsessional about off-target effects; Tracy is not involved in research on the drug or others in the class.
Still, Roche’s overall message was one of supreme confidence in its pipeline – a fact underscored on Oct. 14 by news it is investing $880 million in its expanding its biologics production facilities over the next five years, creating 500 new jobs, as Roche prepares for rising demand.
Despite the optimism, the company is guiding for full year growth similar to that of 2012, about 4%. Sales were up about 6% in the first nine months of 2013 and 8% in the third quarter, but the company’s estimate for the full year remains conservative, due to some one-off effects, including release in the third quarter of about CHF184, set aside for 340b discounts under the U.S. government program that requires manufacturers to offer steep discounts on certain drugs sold to “safety net” hospitals that serve a high proportion of indigent patients.
The Patient Protection And Affordable Care Act of 2010 expanded the discounts to more categories of care providers, but left specifics up to the HHS. Roche had set aside reserves while the details were being worked out; HHS issued a final rule in July exempting orphan disease indications from the mandatory discounts, so Roche will be able to keep the amount it estimated it would have had to discount for the orphan disease applications of affected drugs (Also see "340B Final Rule Keeps Orphan Drug Exclusion Narrow, Counter To Manufacturers’ Request" - Pink Sheet, 22 Jul, 2013.).
Wendy Diller contributed reporting to this article.