ImmunoGen buoyed by T-DM1 surprise
Positive findings for Roche’s Herceptin follow-on, trastuzumab-DM1, has restored confidence in the value of developer ImmunoGen. Investors pushed shares in the Massachusetts group up 27% on Thursday to a nine-year high of $11.80 following news that the antibody-drug conjugate had extended progression-free survival in patients enrolled in its first randomised trial compared to Herceptin plus chemotherapy.
Success in this first-line setting erases much of the disappointment from the failure to try and file for accelerated US approval in a later-line setting based on a single-arm trial demonstrating tumour shrinkage (Roche and ImmunoGen sent reeling by FDA roadblock, August 27, 2010). The surprisingly positive data from a relatively small trial now raises expectations for similarly stellar results from ongoing pivotal trials, while highlighting ImmunoGen as an M&A target once more.
The companies had already released first line data from the trial showing tumour shrinkage and a reduction in side effects from chemotherapy. Achieving improvements in progression free survival, however, was seen by observers as a surprise as the population of 137 patients was thought too small to demonstrate statistical significance.
As such hopes have now been raised for outperforming established drugs in both first and second line settings. The Emilia trial expected to report topline data in early 2012 tests T-DM1 against Xeloda and Tykerb in second line treatment of metastatic or locally advanced HER2-positive breast cancer, with primary endpoints of both overall and progression free survival. Roche is expected to file for US regulatory approval in the middle of 2012.
Meanwhile, the first-line setting may wait a little longer. The three-arm Marianne trial against Herceptin plus paclitaxel or docetaxel expects to report data in 2014 and file in 2015.
ImmunoGen's share price gain is certainly merited when considering the huge potential of T-DM1. The product's net present value of $1.24bn, according to 'EvaluatePharmas NPV Analyzer, is still 50% higher than the company's market capitalisation, even after yesterday's share price surge.
In a January 28 note, analysts from Canaccord wrote that because the phase II first-line trial was not expected to report data until the third quarter of 2011, interest would likely be low until well after the key period around the June ASCO conference. However, release of the topline data now raises the possibility that these results could be included in those sessions, generating further interest in the medical and investor community in T-DM1, ImmunoGen and its antibody-drug conjugate technology.
In a note published today analysts from RBC cautioned that a higher mortality rate in the T-DM1 arm in the phase II trial could result in disappointment on overall survival endpoints, on which regulators have been increasingly been asking for significant improvements.
However, the RBC analysts also note that because T-DM1 is planned to replace the current standard of care, progression free survival coupled with a better safety profile, may be sufficient. T-DM1, which increases the selectivity of trastuzumab to tumour cells thereby reducing its effects on healthy tissues, is expected to be less toxic and reduce the number of side effects suffered by breast cancer patients.
By way of comparison, Avastin was recently withdrawn in breast cancer because it brought additional risks with only modest and questionable improvements in progression free survival (Roche fighting Avastin's corner as support officially withdrawn in breast cancer, December 17, 2010).
For partner Roche, that strategy of replacing the standard of care is an important one. Although the company’s intellectual property estate on its biggest selling products is relatively well protected compared to its big pharma peers, a biosimilar to Herceptin could be one of the first 'copies' of an antibody to reach the western markets - some analysts predict an entry around 2015 in Europe and by 2019 in the US.
Hence the importance, to both Roche and ImmunoGen, of yesterday's positive first-line phase II data which point to T-DM1 emerging as a genuine successor to Herceptin.
|First-line phase II||NCT00679341|