Celebrating its recent elevation into the oncology big leagues, French biopharmaceutical company Ipsen has set itself a steep challenge of accelerating its delivery of innovative products.
The Paris-based company wants to move from its current delivery rate of one new molecular entity or meaningful indication every four years to achieving this every single year. At the sharp end of this challenge is Ipsen’s chief scientific officer and executive VP, research and development, Alexandre Lebeaut.
When it comes to what such a meaningful innovation would look like for Ipsen, Alexandre tells PME “it’s something that will be a game-changer in terms of perhaps changing the practice or acceptance of the indication in a big geography”. From a business standpoint this would equate to a drug or indication delivering €20m or more for the company.
Research strategy
Alexandre has been with the company for five years, having previously held clinical development and medical affairs leadership roles with the likes of Sanofi and Novartis. Last year he was promoted to interim head of R&D and in April he moved up to chief scientific officer and executive VP, research and development.
Since he joined the French biopharmaceutical company he has seen it sharpen the focus of its research strategy, homing in even more on neuroscience, rare diseases and, especially, cancer. Last year the firm’s oncology portfolio accounted for 57% of its €1.6bn group sales, bringing in €904.8m with Somatuline (lanreotide) – a treatment for neuroendocrine tumours as well as the growth hormone condition acromegaly – accounting for over half of that.
2016 proved to be a successful year for the company and its cancer drugs, sales of which jumped more than 22% to catapult Ipsen into the ranks of the top 20 biggest oncology companies for the first time.
Oncology is, unsurprisingly, the biggest cost driver for the company at the moment, with Alexandre noting that its investments in the therapy area are “commensurate with the expectations”.
At the start of this year it acquired Merrimack’s oncology business, including Onivyde (liposomal irinotecan), for $575m. Meanwhile, 2016 saw a licensing deal with Cabometyx (cabozantinib) from Californian biotech Exelixis and an agreement with 3B Pharmaceuticals to develop novel oncology radiopharmaceuticals.
Focusing on the future
In terms of its new oncology products, cabozantinib is very much the firm’s focus. Although marketed as the orphan drug Cometriq for thyroid neoplasms, it’s as Cabometyx in renal cell carcinoma (RCC) where the firm views real potential. Approved in Europe as a treatment for advanced RCC, Cabometyx won backing from NICE at its second try after providing the UK cost-effectiveness watchdog with additional patient benefit evidence and agreeing to discount its price through a patient access scheme.
It currently has a second-line licence in Europe, but Ipsen and its development partner Exelixis have their sights set on a first-line indication and have been pursuing the current standard of care – Pfizer’s Sutent (sunitinib).
Phase II results from its CABOSUN trial, in which it was compared with Sutent in previously untreated advanced RCC, were released at this year’s European Society for Medical Oncology (ESMO) congress in Madrid. Speaking to PME there Alexandre said Ipsen was “thrilled” by the data, not least because it provided “validity of our strategy in terms of investing in this area, in particular with Exelixis, our partner, and looking at the correct drugs”. The new trial of previously untreated patients with advanced RCC showed a 52% reduction in the rate of disease progression or death compared to Sutent, with Cabometyx showing median progression-free survival (PFS) of 8.6 months to its rival’s 5.3 months.
“We beat, if you will, the standard of care,” said Alexandre, adding: “We are superior to sunitinib, which has been on the market for 10 years.” The study also showed evidence of a numerical advantage over Sutent in terms of overall survival. However, Alexandre noted: “The study was not powered to detect the statistical difference in terms of OS, so we will not have this information, but we strongly believe the PFS should be a stronger predictor [of] improving overall survival.”
As the ESMO meeting began, Ipsen received the news that European regulators had validated its application for a first-line licence for Cabometyx. While the company waits to hear from the EMA, there is also work underway to explore the use of Ipsen’s tyrosine-kinase inhibitor (TKI) Cabometyx in combination with some of the biggest immuno-oncology treatments. Leading this work is an agreement with Bristol-Myers Squibb to study a combination of Cabometyx and that firm’s blockbuster immuno-oncology drug Opdivo (nivolumab) and an agreement with Roche to combine Cabometyx with Tecentriq (atezolizumab). “We are open to… more collaborations… potentially showing that cabozantinib could be among the best TKIs to be combined with any other immuno-oncology drugs. That would be an ideal scenario,” he said, but as to whether Ipsen has been talking to Merck & Co about its blockbuster immuno-oncology treatment Keytruda (pembrolizumab), he declined to comment.
Partnering
Oncology naturally features prominently in Ipsen’s in-licensing and partnering plans. “We are really looking more aggressively at some clinically-ready assets, as early as phase I, particularly in oncology,” Alexandre explains, adding: “We are very keen to continue to maintain our leadership in neuroendocrine tumours – any therapeutic solutions [there] would be very interesting to us.”
Also on Ipsen’s radar are opportunities in pancreatic cancer, where it’s keen to maintain the momentum gained from Merrimack’s Onivyde. With relatively few companies involved with the notoriously difficult-to-treat cancer, Alexandre hopes Ipsen can grow its pancreatic activities and add further candidates to its portfolio. Much like its work in liver cancer with Cabometyx, being active in pancreatic cancer allows it to compete in less crowded areas, a tacit acknowledgement that, for now, it lacks the sales muscle to go head-to-head with the very biggest players in tumour types like breast or lung. “We try to [focus on] pancreas, liver and bladder cancer, where there are very few opportunities for patients and where we believe Ipsen could be well positioned.
“We cannot afford to pay a billion every year, but we have a mandate, which is to refill the portfolio, particularly with phase I and phase II assets.” For these Ipsen has three main criteria – they have to be a good strategic fit, financially viable and the firm has to have the capabilities needed to integrate the asset.
To prepare for expansion of its oncology activity, the firm has been on a recruitment drive, building on a research staff that currently numbers 350, hiring more oncologists, gaining skills in modelling and simulations, and developing the expertise required in areas such as predictive toxicology and bioinformatics.
Going global
The company’s ambitions in cancer were boosted by last year’s appointment of new CEO David Meek, who joined the firm from Baxalta where he headed up that company’s oncology division.
Meek is Ipsen’s first non-French CEO since the company’s foundation by Dr Henri Beaufour in 1929. In the present day it has global growth in its sights, building on its 2016 performance that saw its US operations become its largest affiliate by revenue.
Alexandre himself is based in Cambridge, Massachusetts, just one of a number of Ipsen’s executives located outside the company’s homeland. It’s just one manifestation of a desire not to be perceived solely as “a French-centric organisation, but more a global presence”, he explains. Supporting this is the company’s split of its R&D operations between hubs in Cambridge, Paris and Oxford.
Summing up the recent changes at Ipsen, Alexandre concludes: “What has changed is speed. The mindset has changed. We are becoming a global biotech company that is focused on innovation in specialty care. That means that speed is an important factor – patients can’t wait [for innovation, and] particularly oncology patients can’t wait.”