If oncologists and patients who are fighting non-small cell lung cancer could create an optimal cancer fighting therapy, what would be on their list of optimal attributes? That list might include:

  • A drug that would shrink and impede tumors’ growth and reoccurrence. 
  • A targeted therapy that avoids needlessly exposing healthy tissue to powerful cancer fighting drugs.
  • Therapies that minimize adverse effects that arise from the systemic delivery of potent drugs. 
  • A delivery system that is easy, convenient and fast.
  • Lower dosages that save time, money and minimize the physical toll of fighting cancer. 

At Lonza, we recently set out to see if each of these enhancements to fighting non-small cell lung cancer are possible.

One of the earliest questions to address was – are monoclonal antibodies the right treatment to begin with? There are more than a dozen monoclonal antibodies approved for lung indications such as lung cancer with VEGF or EGFR targets, asthma and infections. But all current therapies are systemically delivered.  They are often invasive, expensive and inconvenient for patients as they are delivered in the clinic, put increased time burdens on travel and length of administration. In their current form, monoclonal antibodies don’t meet the optimal attributes desired. But could we develop a monoclonal antibody that is self-administered and locally delivered while maintaining efficacy?

If monoclonal antibodies were a possible answer and the desired attributes were localized delivery and self-administration, could nebulizers be a possible remedy?  The answer was no, as nebulizers presented stability concerns.  However, direct delivery to the lungs is a positive attribute – if it was possible to solve for the respiratory system’s success at preventing the introduction of particles into the lungs. The challenge would be to create a therapy that features molecules with an aerodynamic diameter of between 1-5 microns.  Particles larger than 5 microns are trapped in the mouth and throat, while particles smaller than about 1 micron are exhaled.

We began work with bevacizumab, a monoclonal antibody that inhibits VEGF angiogenesis. It is generally used in combination with chemotherapy and can be a maintenance treatment after chemotherapy is no longer tolerated. But Bevacizumab can cause severe bleeding as a direct result of being systemically delivered, which results in exclusion of a substantial number of potential patients who are at increased risk of bleeding. 

An inhaled bevacizumab drug product could resolve the systemic delivery challenge. Yet, biotherapeutics are very delicate and do not react well to heat or shear exposure (which are often associated with developing inhaled therapies). To develop an inhalable formulation for this program, we suspected that we might need heat and shear to produce droplets and then dry them into a powder.

We employed a spray drying method to enable particle engineering for the inhalation of bevacizumab. It did not damage the biologic, minimized biologic degradation, and used excipients like trehalose to stabilize the formulation. In addition, it allowed for shear exposure to be controlled, heat exposure was limited by evaporative cooling, and the particles were engineered in the critical 1-5 micron range of size. The final product exhibited good aerosol properties; was stable at acceptable ambient temperature for 6 months; and it maintained its anti-VEGF activity. At this stage, all positive outcomes.   

Before going to the clinic, an in vivo efficacy study would give the team the confirmation they needed to continue moving forward. Inhaled bevacizumab was compared to the injected version in combination with the chemotherapy cisplatin in an in vivo study.  The inhaled monoclonal antibodies plus injected chemotherapy did an equivalent job at reducing tumor burden and was, therefore, considered efficacious in vivo. And the inhaled version only needed 10% of the injected dose.  

Lonza now has opened the door to the possibility of better outcomes for patients with non-small cell lung cancer using a spray-dried bevacizumab for inhalation. The monoclonal antibody is delivered through a dry-powder inhaler to patients in lower dosages with fewer side effects. Moreover, the costs are potentially lower, it is a self-administered system that can be used at home, potentially resulting in better compliance and improved outcomes.  Additionally, the probable success of this spray dried inhalation formulation has the potential for positive impacts with other diseases such as asthma, COPD, lung infections and other lung cancers

The spray-dried bevacizumab project illustrates how Lonza brings a unique combination of science, technology, creativity and commitment to its projects. Drawing on 25 years of experience in particle engineering formulation design and encapsulation technologies, the company’s premier particle engineering technology services are tailored to our customers’ molecule target product profiles and delivery devices. Our formulation, analytical and manufacturing teams ensure that development timelines are met and that program risk and complexity is minimized.

In this on-demand talk, Kim Shepard presented Lonza’s approach to formulation and manufacturing of local lung cancer treatments by dry powder inhaler. The presentation discussed two case studies: bevacizumab (a monoclonal antibody) and 5-azacytidine (a small molecule).”

Additional Information and Disclaimer

Lonza Group Ltd has its headquarters in Basel, Switzerland, and is listed on the SIX Swiss Exchange. It has a secondary listing on the Singapore Exchange Securities Trading Limited (“SGX-ST”). Lonza Group Ltd is not subject to the SGX-ST’s continuing listing requirements but remains subject to Rules 217 and 751 of the SGX-ST Listing Manual.

Certain matters discussed in these articles may constitute forward-looking statements. These statements are based on current expectations and estimates of Lonza Group Ltd, although Lonza Group Ltd can give no assurance that these expectations and estimates will be achieved. Investors are cautioned that all forward-looking statements involve risks and uncertainty and are qualified in their entirety. The actual results may differ materially in the future from the forward-looking statements included in these articles due to various factors. Furthermore, except as otherwise required by law, Lonza Group Ltd disclaims any intention or obligation to update the statements contained in these articles.

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