ILAP: Improving access to innovative oncology treatments

In November 2022, the Medicines and Healthcare products Regulatory Agency (MHRA) Innovation Passport was awarded to Boehringer Ingelheim’s investigational BI 907828 in de-differentiated liposarcoma (DDLPS), a rare and aggressive oncology indication for which there has been no new first-line treatment in over forty years.

In this Q&A, Dr Christoph Zehendner, Medical Director for Boehringer Ingelheim UK and Ireland speaks to EPR about the significance of the Innovation Passport and Innovative Licensing and Access Pathway (ILAP), in helping to address the limited treatment options for rare cancers.

The Innovation Passport designation is the first step in the ILAP. It aims to accelerate how quickly patients can gain access to innovative medicines.

What other treatments have undergone novel approval processes?

The ILAP pathway was launched in January 2021 supporting innovative approaches to the safe, timely and efficient development of medicines to improve patient access. Our investigational treatment BI 907828 is the first asset from Boehringer Ingelheim for which ILAP was awarded.

What was significant about Boehringer Ingelheim receiving this ILAP designation?

We have defined a number of investigational therapies that are following an accelerated development path. People affected by the ultra-rare form of soft tissue sarcoma, de-differentiated liposarcoma (DDLPS), have had no new first-line treatment options for over 45 years.

The Innovation Passport designation recently awarded to BI 907828 represents the first step in the ILAP, which aims to accelerate the time medicines reach patients to improve access to innovative treatments where there is a significant unmet need.

What makes BI 907828 or MDM2-p53 antagonists more broadly promising candidates for cancers such as liposarcoma?

BI 907828 blocks the interaction between two proteins known as MDM2 and P53. This can lead to direct action on tumour cells and activate the body’s own immune response against the cancer. High levels of MDM2 are a feature of many cancers.

For example, more than 90 percent of all de-differentiated liposarcoma cases will show this. Other cancer types may also show this albeit to a lesser extent. Our investigational treatment has the potential to be relevant in several of these MDM2 driven cancer types.

Can you provide an update on ongoing studies?

An update on Phase I data on BI 907828 in advanced solid tumours was recently presented at the European Society for Medical Oncology (ESMO) Annual Meeting. We reported safety and efficacy data from 107 treated patients, including 39 patients with de-differentiated liposarcoma.

In terms of efficacy, we recorded disease stabilisation (ie, tumours did not grow much relative to when patients joined the study) in 84 percent of patients (79 out of 94) and in 89 percent of de-differentiated liposarcoma patients (32 out of 36) that could be evaluated.

We also saw some clinically meaningful tumour shrinkage in 13 percent of patients overall (12 out of 94) and in 14 percent of de-differentiated liposarcoma patients (5 out of 36) that could be assessed.

The preliminary median progression-free survival for all DDLPS patients was 8.1 months. This is very encouraging in this heavily pre-treated patient population and hard to treat disease.

Our global Brightline-1 Phase II/III trial of BI 907828 compared to current standard of care doxorubicin for de-differentiated liposarcoma (not previously treated with other drugs) is ongoing. We hope to complete enrolment in 2023.

How can working closely with regulatory authorities support development of treatments in areas of unmet need? 

It provides an opportunity to engage with regulators early to expedite the availability of a promising medicine to patients in an area of high unmet need.

We look forward to the next stage, working with the MHRA, National Institute for Health and Care Excellence (NICE) and their partners to develop our roadmap to licence.

What are the key challenges for drug developers in the oncology field, particularly in rare diseases?

A key challenge is being able to identify and recruit enough patients to be able to conduct randomised controlled trials in rare oncology disease indications. Often this is also dependent on correct diagnosis of these patients and identification of rare genomic abnormalities that drive these cancers.

What have been the most significant developments in oncology over the past few years? 

Targeted therapies are increasingly becoming the standard of care for many oncology indications. These are aimed at disease causing processes within specific cancer types and provide a more effective and personalised treatment approach for patients.

Immunotherapies primarily as checkpoint inhibitors but also as T cell engagers or CAR-T therapies, which harnesses the power of the immune system, have become available as standard treatment in various cancer indications.

About the author

Dr Christoph Zehendner is the Medical Director for Boehringer Ingelheim UK and Ireland. He is responsible for driving innovation across areas of high unmet patient need, while also developing sustainable healthcare partnerships. Christoph has previously held various Therapeutic Area Leadership roles in Respiratory, Oncology and most recently Interstitial Lung Disease at Medical Affairs in Boehringer Ingelheim Germany. Christoph holds a specialisation in Molecular Medicine (Habilitation).