Bristol-Myers Squibb (BMY) and Eli Lilly (LLY) announced Thursday that they had settled their dispute over rights to necitumumab, formerly known as IMC-11F8, an antibody which must rank as one of the most squabbled over in recent times.
As a potential Erbitux follow-on, a product that itself is important to both partners, the desire to share in the action around any improved version is understandable. Still, phase III trials have only just started, in lung cancer, and necitumumab has a long way to go before BMS and Lilly know whether they are backing a winner.
Fully human
Unlike Erbitux, which is part human, part mouse, necitumumab is a fully human IgG1 monoclonal antibody, although they both target epithelial growth factor receptor, or EGFR. Theoretically this could mean it is safer, for example with fewer hypersensitivity side effects such as skin rash, and need dosing less frequently. The companies will also be hoping to prove it is better at fighting tumours.
The compound was originated by ImClone, which was bought by Lilly in 2008. The acquisition was struck largely for access to Erbitux, which is sold in Europe by Merck KGaA (MKGAY.PK) and by BMS in the US.
Back in 2006, Merck tried to argue that its deal over Erbitux included the rights to develop and commercialise any follow-on products, IMC-11F8 in particular, outside the US, but an arbitrator ruled in ImClone’s favor.
The takeover battle for ImClone a couple of years later, which was triggered by a bid from BMS and eventually won by Eli Lilly, meant disagreements over rights to necitumumab resurfaced. BMS asserted it had full rights in the US, under the terms of the Erbitux deal; ImClone disagreed.
Arguably, access to this compound was a big motivator that prompted BMS to try to take control of ImClone in the first place (Wrangles over Erbitux follow-on central to ImClone takeover, September 12, 2008). It would clearly want control of any future competition to one of its biggest selling products.
Equal share
As EP Vantage discussed at the time, the terms of the BMS-ImClone deal indicated that rights in the US, Canada and Japan should be split 50:50, and this is exactly what was announced yesterday.
Both companies will share in the cost of developing and potentially commercializing necitumumab in the US, Canada and Japan, whilst Lilly maintains exclusive rights to necitumumab in all other markets.
Pivotal trials have already started. The first, called Inspire, is in nonsquamous lung cancer, pitting the drug in combination with the chemotherapy agents cisplatin and Lilly’s Alimta against chemotherapy alone, with overall survival as the primary endpoint. It is aiming to enrol 947 patients with advanced lung cancer and could be complete by early 2012.
The second trial, which has yet to start and will be called Squire, will recruit patients with advanced squamous lung cancer. Necitumumab plus cisplatin and gemcitabine will be pitted against the two chemotherapies alone, again seeking to recruit 947 patients with overall survival as the primary endpoint, and possible completion in mid-2012.
Pivotal trials in colorectal cancer, where Erbitux is entrenched, are set to start soon, according to the companies, although Cowen analysts recently wrote that a phase III study in colon cancer had been discontinued, but no record of this can be seen on clinicaltrials.gov.
Hurdles
It is interesting that the companies have chosen to pursue lung cancer as their primary indication, given that Erbitux, and to a certain extent its main anti-EGFR rival Vectibix, have struggled to generate convincing data in this setting.
Merck failed to win approval for the drug in Europe late last year, with regulators remaining unconvinced about the drug’s efficacy in this cancer. BMS and Lilly will be well aware of the need for necitumumab to generate results that significantly outstrip Erbitux if they are to win approval.
Additionally, Morgan Stanley analysts also point out that comparative effectiveness assessments will be happening by the time it reaches the market, which could be another barrier to face.
Risk burden
Either way, it will probably be some time before analysts start attributing significant value to this compound.
Although some analysts have pencilled in sales forecasts - EvaluatePharma consensus has sales of $44 million by 2014 under Eli Lilly – the product’s value will be very hard to estimate accurately until it can be held up against Erbitux, as the companies will no doubt try to market the drug as a “better than."
Still, getting this compound to market, and selling it once it's there, could well be a long and arduous road. At a time when companies of all sizes are increasingly keen to share risk, both companies could come to appreciate having another party to bear the burden of this project.
