It is more than 18 months since a US FDA advisory panel strongly backed the resumption of work on a once promising class of pain drugs – anti-nerve growth factor antibodies – but despite this the handful of relevant projects remain stuck in limbo.
However, Lilly’s quiet disclosure of the potential terms of a deal with Pfizer over tanezumab, the most advanced of these antibodies, hints that this might be about to change. At some point next year the FDA will rule on the adequacy of Pfizer’s additional preclinical data, and a positive decision might reinvigorate the class.
This is not to say that anti-nerve growth factor MAbs will again attract the blockbuster valuations they once boasted. At one stage several were the subject of lucrative licensing deals, but this optimism was cut short when in 2010 the US FDA halted work on the entire class after reports of bone and joint destruction in the tanezumab programme.
The FDA advisory panel offered renewed hope last year, when it voted 21-0 in favour of companies restarting work in arthritis, and 20-1 in other painful conditions (Therapeutic focus – Return of anti-NGF class gets FDA panel's backing, March 13, 2012). But last December the agency slapped a new clinical hold on the class – this time on fears of peripheral nervous system effects seen in animal studies.
Now hope springs again. Pfizer says the clinical hold on tanezumab was lifted at last in July, although development remains stalled pending a final analysis of preclinical data.
It is based on this hope that Lilly struck. The group did not make a formal announcement – presumably because the deal’s terms will only kick in if the FDA’s response to the data is satisfactory – but in a regulatory filing it outlined the tie-up’s potential financial terms.
Assuming Lilly and Pfizer continue the deal after the FDA ruling, the former has agreed to pay $200m up front, followed by up to $350m and $1.23bn in development and sales-based milestones respectively. Development costs will be shared equally, and tanezumab will be commercialised jointly for osteoarthritis, chronic low-back pain and cancer pain.
The alliance could be seen as yet another example of Lilly throwing large amounts of cash at an extremely risky asset, though this view should be tempered by the fact that the tie-up is effectively contingent on an FDA green light. If the deal were included in the current year it would feature as one of the most lucrative so far, both in terms of up-front fee and overall value.
Nerve growth factor has been found to be elevated in patients with acute and long-term pain, and its blockade was thus thought to hold promise in treating chronic pain – particularly in osteoarthritis, which is not responsive to conventional pain-killers.
But the pipeline is thin, and in addition to tanezumab numbers at most four other clinical projects, whose developers will no doubt pay close attention to Pfizer’s progress. Johnson & Johnson is the only company actively running a study – fulranumab is in a 94-patient phase II trial in cancer pain, and the company tells EP Vantage that it remains in talks with the FDA over other indications, which remain on hold.
Should a bounce from the long delay be imminent Lilly might find itself in pole position, though the group’s investors might well ask themselves why Pfizer did not just retain tanezumab for itself. The fact that the world’s biggest pharma company was willing to give up a large chunk of the asset should temper some of the enthusiasm.
|Anti-nerve growth factor MAbs: a thin pipeline|
|Tanezumab||Pfizer/Lilly||Phase III||All studies completed or terminated.|
|Fulranumab (AMG 403)||Amgen/J&J/Takeda||Phase II||Cancer pain trial (NCT00929188) recruiting.|
|ABT-110||AbbVie||Phase I||One study completed.|
|Fasinumab (REGN475)||Sanofi/Regeneron||Suspended - phase II||All studies completed or terminated.|
|MEDI-578||AstraZeneca||Abandoned - phase I||Osteoarthritis of the knee trial terminated.|
|CRB 0089||Rottapharm||Preclinical||"Exploratory development" for OA pain and chronic pain.|
(This story was amended to clarify the status of the hold on tanezumab and fulranumab.)