Scrip: industry news and insights
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Sanofi will make key regulatory submissions in 2018 aimed at bringing its immuno-oncology portfolio up to speed; the company's head of oncology development Joanne Lager tells Scrip about the company's PD-1 strategy and promising early-stage R&D candidates.
Sanofi is not a top player in the IO market, having fallen behind the likes of Merck & Co. Inc., Bristol-Myers Squibb Co. and Roche, which have taken the lead with their approved checkpoint inhibitors for various cancer types. Still, the drug maker – better known for its diabetes portfolio – is betting heavily on the IO space and expects its pipeline to make advances in 2018.
JOANNE LAGER, HEAD OF ONCOLOGY DEVELOPMENT AT SANOFI
"Our oncology pipeline has increased in recent years; it has become an area of higher focus for us within the company and something we are talking more about," Lager said in a recent interview. "We have reemerged as an oncology company and a company with potential strengths in the immuno-oncology area." The hiring of Yong-Jun Liu in 2016 as Sanofi's head of research, with his expertise in immunology and oncology, reinvigorated the company's early pipeline, Lager said.
Sanofi's oncology pipeline will see two major product filings this year.
The company's oncology strategy is heavily reliant on its in-house programmed cell death protein 1 (PD-1) inhibitor cemiplimab, which it expects to file with regulators in Europe in the first half of this year and for which it will complete a rolling BLA application to the US FDA in the coming months. Cemiplimab, developed through a partnership with Regeneron, will be the backbone of Sanofi's emerging immuno-oncology pipeline. The company is targeting a skin cancer indication for cemiplimab's first filing, but the product is in late-stage development for other diseases, including the highly competitive non-small cell lung cancer market (NSCLC).
Sanofi's other key development compound, isatuximab, an anti-CD38 compound currently in pivotal trials for multiple myeloma, is expected to be submitted to regulators in the fourth quarter of 2018 for relapsed/refractory disease.
Getting In The PD-1 Game
Looking at the IO field, Lager said transforming growth factor beta (TGF-β) therapies and cluster differentiation 38 (CD38) antibodies had emerged as important options for patients with resistance to PD-1 therapy, as potential combination partners with strong rationales. "We are happy now to have drugs against those three targets within our portfolio," she said.
To be able to pursue its combination strategy in IO, Sanofi first needs to get its PD-1 inhibitor approved. Lager said cemiplimab was selected to be similar to the PD-1 drugs on the market, such as Merck's Keytruda (pembrolizumab). However, "we are looking to differentiate cemiplimab through our development approach," she noted.
One of Sanofi's methods with cemiplimab is to find treatment areas that have not already been exploited by checkpoint inhibitors. Its lead indication for the PD-1 antibody is metastatic cutaneous squamous cell carcinoma (cSCC). None of the current marketed PD-1 or program death-ligand 1 (PD-L1) products is approved for this indication, and the development pipeline includes only Phase I and Phase II programs. There is no immediate IO competition for late-stage cemiplimab in this disease.
"We have prioritized moving forwards with cemiplimab in indications where there are opportunities for us to be the first, and where we can bring checkpoint inhibitors to new groups of patients," Lager said, adding that there was strong evidence patients with cSCC tumors could benefit from checkpoint inhibition.
"Probably it is an underestimated disease because there isn't great epidemiology to understand how many patients have it, and there is really no good therapy for patients with advanced disease," Lager said.
As well as cSCC, Sanofi has Phase III programs ongoing for cemiplimab in cervical cancer – another area where there is limited competition from other PD-1/PD-L1 developers – and NSCLC.
NSCLC is a very competitive space for IO drug developers and does not fit with Sanofi's strategy of targeting cancer indications where there is limited exploration with checkpoint inhibitors. Lager said this indication was more of a test case for cemiplimab. "Part of the reason we are moving forward with the three Phase III trials in lung cancer is really to be able to establish [cemiplimab] as an option in the NSCLC space so that we can sell combinations in the future," she said.
Sanofi is evaluating several other indications for cemiplimab and "will continue to look for opportunities where the competition is not so active," Lager added. The company expects to launch the PD-1 therapy in cSCC in the US by the end of 2018.
|cSCC||Rolling BLA application|
|Cervical cancer||Phase III|
|Basel cell carcinoma||Phase II|
|Brain cancer||Phase I/II|
|Prostate cancer||Phase I/II|
|Hematologic cancer||Phase I|
|Renal cell carcinoma||Phase I|
|Solid tumors||Phase I|
Combinations Are Key
Sanofi also plans to make a first regulatory submission for isatuximab, an anti-CD38 antibody, in multiple myeloma by the end on the year. "With this drug, we are also exploring combinations with checkpoint inhibitors and are launching trials in multiple myeloma and eight solid tumor indications with those combinations," Lager highlighted.
Sanofi expects cancer combinations to drive its future IO portfolio, a strategy being used by all the big oncology players. As well as having combination trials planned for its internal pipeline, the big pharma will continue to seek deals with other developers. "There are advantages to being able to do things within our own pipeline but we are also looking at external collaborations," Lager said.
Quick Decisions On Novel Concepts
Lager said the biggest challenge for Sanofi's oncology business was the stiff competition in cancer drug development and whether the company could bring forward novel technologies with the potential to be first-in-class or best-in-class. For many of its drug candidates this is achievable, Lager said.
"Can we get to proof-of-concept faster so that we can have an advantage in terms of timing to get our drugs to market first?" Lager said this was one of the key tasks for Sanofi's IO pipeline. "We want to provide new options to patients that really provide significant benefit over what is currently available," she said.
Examples of earlier-stage oncology candidates in Sanofi's pipeline that it hopes will help it meet these challenges include its selective estrogen receptor degrader (SERD) candidate and antibody-drug conjugate platform. Sanofi's SERD asset recently entered first human studies for the treatment of breast cancer. "We have preclinical data that is supportive to this being a best-in-class option. We are using biomarkers and imaging techniques to accelerate dose escalation so that we can get to proof-of-concept faster," Lager noted.
Lager added, "We are excited about our portfolio in oncology and it is a major focus at Sanofi to accelerate launches and decisions for the early portfolio, so that we can make quick decisions about further studies and investments."
Sanofi's early oncology pipeline includes assets with various modes of action and Lager highlighted two new drugs due to enter the clinic this year. The first is a T-cell engager bi-specific antibody targeting CD 123, which is expressed on myeloid leukemia; this asset will enter the clinic in the first half of this year. The second is an immune-stimulatory mRNA drug that can be given by intratumoral injection, and works by turning the tumor into its own vaccine to stimulate an immune response. It will enter the clinic in the second half of 2018.
In total, Sanofi expects six pre-clinical oncology programs to enter Phase I in 2018.
In late 2017, during an R&D and innovation day, Sanofi noted that 65% of its pipeline programs were for first-in-class therapies. Also, 50% of its R&D candidates are biologics and vaccines, 22% are novel technologies and the remaining programs are small molecules.
The French firm's six key development areas are immunology, multiple sclerosis and neurology, oncology, rare diseases, diabetes and cardiovascular, and infectious diseases.
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