Lilly’s ramucirumab comes off the bench with a clutch single

Ramucirumab might not have had a starring role in many analysts’ forecasts for Lilly’s post-patent-cliff recovery plans, but an apparent success in its first phase III study has caused investors to sit up and take note.

The topline data, from a second-line monotherapy trial against gastric cancer, build on momentum from what has been viewed as a positive hit in Alzheimer’s disease with solanezumab – however shaky that result might actually be. With the previously failure-prone Lilly now up 26% since the start of the year it seems that ramucirumab will not remain under the radar for much longer.

The phase III trial, Regard, has hit its primary endpoint of showing a statistically significant improvement in overall survival compared with best supportive care alone, as well as prolonging progression-free survival – a key secondary. The only other monoclonal antibody drug to hit an OS endpoint in gastric cancer is Roche’s Herceptin, which was approved based on less than a two-month improvement.

Bloated

Yesterday’s surge meant that Lilly’s already bloated market cap put on another $2.4bn despite no details having being released about the magnitude of ramucirumab’s survival improvement, which will clearly show whether it is clinically relevant.

As a result there are no clues as to whether the Regard study alone might be used in a regulatory filing – it had initially been designed as a “supportive” trial – or whether submission will also require data from Rainbow, a larger phase III gastric cancer study expected to read out next year. But ISI Group’s Mark Schoenebaum says if the Regard results are strong the FDA will have a “hard time” not approving ramucirumab.

Consensus data compiled by EvaluatePharma estimates a 2015 launch for the drug, with combined sales reaching $326m in 2018, although some analysts are frantically reviewing their forecasts after yesterday’s announcement. The project currently carries a 75% risk-adjusted NPV of $1.3bn.

Leerink Swann said data from Regard showed potential for an accelerated approval and boded well for Rainbow; the bank put the gastric cancer opportunity at $500m to $1bn. Mr Schoenebaum agreed, adding that breast and liver cancers could each represent similarly sized opportunities.

He suggested that ramucirumab had until now sailed under the radar because it had effectively been fast-tracked from phase I into phase III; only interim data were released from Phase II studies, in first-line NSCLC, which showed median PFS of 7.85 months, and renal cell carcinoma (8.3 months).

Avastin points the way

Ramucirumab, previously known under the lab code IMC-1121B, was acquired by Lilly through the takeover of ImClone Systems, which had isolated it using technology from Dyax.

Part of the reason for the latest optimism is the parallel that some have drawn between Lilly's antibody and Roche’s blockbuster Avastin; while Avastin is a monoclonal antibody against the VEGF ligand, ramucirumab blocks the VEGF receptor itself.

However, Avastin missed statistical significance in its first-line phase III gastric cancer study, Avagast, despite showing a numerical OS improvement. Leerink Swann and ISI agree that in a study the size of Regard a two-month improvement in OS would be both statistically significant and clinically meaningful.

Clinicaltrials.gov lists six current phase III studies for ramucirumab in oncology indications, and these are due to be completed over the coming years, with 2013 seeing data in gastric, hepatocellular and colorectal cancers. Ramucirumab is definitely not yet a star player – such an accolade would depend on success in additional cancers and on its use in the first-line setting increasing.

But the positive surprise the project has just delivered positions it to play an important supporting role.

Phase III trials of ramucirumab
Study Detail Trial ID
Regard 355 gastric cancer patients, second line, single agent NCT00917384
Rainbow 665 gastric cancer patients, second line, addition to paclitaxel NCT01170663
Reach 544 hepatocellular carcinoma patients, second line, single agent NCT01140347
 – 1,050 colorectal cancer patients, second line, addition to FOLFIRI NCT01183780
 – 1,242 NSCLC patients, second line, addition to docetaxel NCT01168973
 – 1,144 breast cancer patients, first line, addition to docetaxel NCT00703326

To contact the writer of this story email Jacob Plieth in London at jacobp@epvantage.com

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