Boehringer Ingelheim, Inventiva Collaborate to Find New Idiopathic Pulmonary Fibrosis Treatments

by | June 6, 2016

Boehringer Ingelheimlogo Germany based Boehringer Ingelheim and France based Inventiva have announced a new multi-year research and drug discovery collaboration and licensing agreement.

Under the agreement, Inventiva and Boehringer Ingelheim teams will work on validation of a new therapeutic concept to discover new medicines for treating idiopathic pulmonary fibrosis (IPF) and other fibrotic diseases. The partnership will combine Inventiva’s deep knowledge and proprietary technologies in the transcriptional regulation and fibrosis fields with Boehringer Ingelheim’s discovery, clinical development experience and development capabilities of new therapeutic agents.

“We are very proud to enter into this collaboration with Boehringer Ingelheim, a company well-reputed for its excellent research and development skills in the field of fibrosis, and particularly Idiopathic Pulmonary Fibrosis,” said Inventiva’s co-founder and CSO Pierre Broqua. “We plan, alongside developing our own pipeline, on pursuing our strategy of establishing collaborative research partnerships with the world’s biggest pharmaceutical companies. This new partnership further testifies to Inventiva’s expertise and contributes to strengthening our position as a leading and innovative actor in the field of fibrosis.”

Clive R. Wood, Boehringer Ingelheim’s senior corporate vice president of Discovery Research, said the company looks forward to working with Inventiva’s team to develop breakthrough IPF therapies.

“We are impressed by Inventiva’s research and drug discovery competencies and deep knowledge of the field. We firmly believe that joining forces with Inventiva will enable us to foster translation of an aspirational new therapeutic concept into eagerly awaited new therapies for patients,” Wood said.

IPF is a rare, debilitating, and fatal disorder in which lungs become progressively scarred over time. As a result, patients with IPF experience shortness of breath, cough, and have difficulty participating in everyday physical activities.

Current treatments for IPF include oxygen therapy, pulmonary rehabilitation, and lung transplant. The most common interstitial lung disease worldwide, IPF affects an estimated three million people and poses a major public health threat.

The IPF median survival rate is two to three years after diagnosis; 70% to 80% of patients die within five years of diagnosis. To date, the cause of IPF is unidentified and, despite recent progress, treatment is limited.

Boehringer Ingelheim says its collaboration with Inventiva exemplifies the company’s increasing focus on external innovation and will build on its track record in IPF drug development. For example Boehringer Ingelheim has successfully developed nintedanib (OFEV) , a small molecule tyrosine kinase inhibitor, which has been approved and marketed globally for treating IPF in adults. The company will be the collaboration partner responsible for clinical development and commercialization of potential new drug candidates.

OFEV blocks multiple pathways that may be involved in the scarring of lung tissue. Its safety and effectiveness were established in three clinical trials of 1,231 patients with IPF. The decline in forced vital capacity — the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible — was significantly reduced in patients receiving OFEV compared to patients receiving placebo

Boehringer Ingelheim says OFEV reduces the risk of acute IPF exacerbations, and in the INPULSIS-2 trial published in the New England Journal of Medicine, risk of first acute IPF exacerbation over 52 weeks was significantly reduced in patients receiving OFEV compared with placebo; in the INPULSIS-1 trial, there was no difference between the treatment groups.

INPULSIS-1 and -2, involved 1,061 people with IPF, and met the primary endpoint: reduction in the annual rate of decline in forced vital capacity (FVC) over 52 weeks. In these trials, nintedanib reduced the annual rate of FVC decline compared to placebo by 48% in INPULSIS-1 and by 55% in INPULSIS-2.

Boehringer Ingelheim explains that in the pooled analysis of the INPULSIS trials, a lower risk of first acute IPF exacerbation was observed in patients receiving OFEV compared with placebo, and that OFEV slows IPF progression with an approximately 50% reduction in decline of lung function measured across a broad range of IPF patient types. This included patients with early disease (minimal lung function impairment), limited radiographic scarring (no honeycombing) on high resolution computed tomography (HRCT), and those with emphysema. Side effects with OFEV can be effectively managed in most patients. Diarrhea was the most frequently reported side effect.

The company said OFEV targets growth factor receptors, which are involved in the mechanisms by which pulmonary fibrosis occurs. Most importantly, the drug inhibits platelet-derived growth factor receptor (PDGFR); fibroblast growth factor receptor (FGFR); and vascular endothelial growth factor receptor (VEGFR).

It is believed that OFEV reduces disease progression in IPF and slows the decline in lung function by blocking the signaling pathways that are involved in fibrotic processes, citing scientific study references.

The US Food and Drug Administration approved OFEV for treatment of IPF in October 2014, after granting the drug fast track, priority review, orphan product, and breakthrough designations. The European Commission (EC) approved nintedanib for treatment of IPF in January 2015, following an expedited review and positive CHMP opinion. Nintedanib is also marketed in the EU under the brand name OFEV.

Klaus Dugi, chief medical officer of Boehringer Ingelheim, said approval in the EU is a big step toward meeting unmet needs in IPF.

“Patients suffering from this chronic, debilitating disease can now be offered a new treatment option that has been shown to have a clinically meaningful effect on their disease,” Dugi said. “This approval is another milestone in Boehringer Ingelheim’s ongoing efforts with regard to innovation in rare diseases in general and our continuing research for the benefit of patients affected by such a dreadful disease as IPF in particular.”

Health Canada approved OFEV/nintedanib to treat IPF in adults in July 2015.

Under the new collaboration agreement with Boehringer Ingelheim, Inventiva will receive an upfront payment and will be eligible to receive research funding, potential research projects; development, regulatory and commercial milestone payments of up to €170 million; and tiered royalties on net sales of the products that result from the partnership. Full financial details remain undisclosed.

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