Mirati debuts KRAS data
Mirati presented long-awaited data for its KRAS inhibitor MRTX849 this week at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics. Preliminary Phase I/II results showed a 50% response rate in six non-small-cell lung cancer (NSCLC) patients and a 25% response rate in four colorectal cancer (CRC) patients.
These data position early evaluation of MRTX849's efficacy on a par with Amgen's competing KRAS inhibitor AMG510 (ViewPoints: Mirati meets expectations in KRAS showdown).
The two drugs are arguably the industry's most heavily valued oncology pipeline agents, owed in part to the previous assertion that KRAS was an 'undruggable' target and its potential role as a biomarker in multiple cancer types.
Competition in this space is expected to intensify, with Boehringer Ingelheim also presenting early data for its own agent this week - ViewPoints: Boehringer Ingelheim throws – potentially big – hat in KRAS ring.
Another cancer victory for AstraZeneca, but will it count for much?
AstraZeneca's impressive run of form in oncology continued this week with confirmation that its POSEIDON study met one of two co-primary endpoints.
The company said that the combinations of Imfinzi and chemotherapy, and Imfinzi, tremelimumab and chemotherapy both improved progression-free survival (PFS) versus chemotherapy alone in patients with previously untreated metastatic NSCLC. The study will continue with overall survival data expected to read out next year.
The results are notable as this is the first pivotal-stage study in which AstraZeneca's CTLA-4 inhibitor tremelimumab has been shown to be effective, though whether it is a necessary component in future treatment regimens will remain unclear until full data from POSEIDON are presented (and performance of the triple combination is compared to Imfinzi plus chemotherapy) - ViewPoints: POSEIDON offers upside surprise for Imfinzi but not necessarily path to market in 1L NSCLC.
It is also debatable whether late comers to the first-line NSCLC market can pick up anything other than a niche share given the dominance of Merck & Co.'s Keytruda.
One expert shared his views with us…KOL Views Results: Leading oncologist separates I/O contenders from pretenders in battle for NSCLC supremacy
Q3 in brief
Indeed, global sales of Keytruda swelled to $3 billion for the third quarter, Merck reported this week, driven primarily by continued uptake in NSCLC. The company said that eight in 10 previously untreated patients with metastatic disease now receive a Keytruda-based regimen.
Like Merck, both Pfizer and GlaxoSmithKline raised full-year guidance on the back of strong sales in the third quarter, driven in particular by Ibrance (breast cancer) and Shingrix (shingles vaccine), respectively. Bristol-Myers Squibb modestly raised its full year guidance on the back of Q3 results, which were boosted by stronger than expected sales of Eliquis (stroke) and Sprycel (leukaemias). Sanofi beat revenue expectations with notable outperformance seen for its vaccines business and Dupixent (atopic dermatitis)
Amgen also raised its full-year revenue forecast, but saw sales in Q3 decline year-on-year, in part due to biosimilar competition. Gilead Sciences swung to a loss due to expenses relating to the R&D partnership it announced with Galapagos in July. Its third-quarter performance otherwise is likely to prompt further anticipation for M&A or aggressive in-licensing to build out its late-stage pipeline.
Celgene, which remains on-track to become part of Bristol-Myers Squibb by the end of 2019, posted a solid set of results. Pipeline updates relevant to the contingent value rights (CVR) component of Bristol-Myers Squibb’s offer all moved in the right direction.
A week ago Novartis appeared to have put its recent Zolgensma-related woe firmly in the rear view mirror by announcing higher-than-expected Q3 sales of the spinal muscular atrophy (SMA) gene therapy. Confirmation on Wednesday, however, that the FDA has placed a partial hold on a high-dose, intrathecal version of Zolgensma being evaluated in older patients with type 2 SMA is a setback.
To what extent remains unclear at this juncture, though analysts at Stifel described the disclosure as "the latest mishap for the Zolgensma programme," in reference to earlier 'data manipulation issues' raised by the FDA pertaining to preclinical results included as part of Novartis' regulatory application. Analysts at Guggenheim suggested in a note to investors that toxicity concerns leading the partial hold were first identified in March.
There appears to be no threat to intravenous Zolgensma - approved for the treatment of SMA in patients under the age of two - being pulled from the market, though delays to Novartis' development programme for older SMA patients will be seen as a positive for Biogen (which markets Spinraza) and Roche/PTC Therapeutics (which are shortly expected to file the oral treatment risdiplam with regulators).
Biogen appears to be throwing a considerable number of eggs into one basket with its recently announced decision to file aducanumab for the treatment of Alzheimer's disease. Approval of Vumerity, essentially a rebooted version of its blockbuster multiple sclerosis treatment Tecfidera with better gastrointestinal tolerability, should therefore provide Biogen with a lower-risk opportunity to boost near-term revenue.
To what extent physicians will move patients from Tecfidera to Vumerity remains unclear, though a snap-poll we ran during the summer suggested that around a third of Tecfidera users could end up receiving the new agent instead.
Bernstein analysts came out in support of Biogen's strategy to refile aducanumab this week, suggesting that while the data is "not conclusive it is consistent with the science-to-date (or at least not negated by it)."
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