Blog: Gene Therapy and Rare Disease

Written by Bob Smith

Key Points

  • Bob Smith is an accomplished biopharmaceutical executive with over 30 years of experience.
  • He leads Pfizer’s Gene Therapy and Rare Disease portfolio from a strategic development and operational implementation perspective.
  • This blog has been adapted from Mr. Smith’s recorded presentation for the 2022 Symposium.

Pfizer’s Gene Therapy Program
Pfizer aims to be the industry leader in gene therapy and has been investing in the field since 2014 with the view that the technology could be broadly applicable to patients with genetically defined diseases. There are more than 7,000 rare diseases; of those, more than 80% have a genetic etiology and about half of them primarily affect infants and children, unfortunately carrying significant morbidity and early mortality. Gene therapy has the potential to deliver transformational clinical benefits by changing the course of the underlying genetic etiology of the disease. In addition to a broad portfolio of more than 20 preclinical programs, Pfizer has three programs in early clinical development and three programs in phase three development. The company is expanding its gene therapy platform beyond traditional gene addition (using viral-mediated vectors) to more advanced second- and third-generation gene and base editing technologies.

Focused Ultrasound and Gene Therapy
Focused ultrasound may provide solutions to various gene therapy delivery challenges, which include delivering the right dosage of genes into the right tissues and the right cell types within that tissue. The technology has the potential to improve the delivery of viral-mediated gene therapies and enable the use of nanoparticles that encapsulate a gene of interest and deliver it to specific cells within a specific tissue at the right dose. It is exciting that focused ultrasound provides a new and novel way to noninvasively deliver drugs and other pharmaceutical agents precisely to focal points within the body in a very high concentration. The use of focused ultrasound could also decrease systemic side effects and other toxicities involved in traditional gene delivery approaches.

Using focused ultrasound to reversibly open the blood brain barrier could address a significant challenge in delivering gene therapies and other genetic therapies in central nervous system disorders. Focused ultrasound can also enhance the permeability of stroma and other tissues, such as in the pancreas, where it has been difficult to achieve good clinical benefits. In addition, focused ultrasound can enhance the permeability of cell membranes and activate the release of compounds from nanoparticles.

Public-Private Partnerships
Partnerships between medical device manufacturers and academic teams developing new therapeutics are needed to create products of interest to the pharmaceutical industry. Collectively, the field must prioritize which clinical indications would be worthy of partnerships between academic groups, medical device manufacturers, and potential biotech and pharmaceutical companies. Companies like Pfizer are interested in developing drugs that treat certain types of diseases and those that will deliver transformational benefits that change patients’ lives. Pharmaceutical companies invest in new technologies that fit within the company’s long-term, strategic vision. The investment timeline cannot be decades, but it should allow for an appropriate amount of research and clinical development. The new technology must have a sound regulatory strategy and a solid, multi-stage clinical trial plan that is based on strong preclinical data and a positive risk-benefit profile for patients in need. The new product must then be deliverable through the pharmaceutical company’s manufacturing and commercial distribution infrastructures.

Pharmaceutical Company Investments
To mitigate risk for the investing pharmaceutical company, its executives evaluate the cost of failure versus the potential benefit of having a product successfully navigate the research and development continuum and ultimately benefit patients. These executives are also interested in the intangible aspects of a new technology, such as attracting the appropriate level of scientific expertise to build relationships with the key opinion leaders and patient communities that may be impacted by the diseases. Pharmaceutical companies conduct scientific and technical due diligence to determine whether a technology could be complementary or synergistic with its overall therapeutic portfolio. They need a high degree of confidence that they can deliver a product that will benefit patients and the overall health care system.

An accomplished biopharmaceutical executive with over 30 years’ experience, Bob Smith leads Pfizer’s Gene Therapy and Rare Disease portfolio from a strategic development and operational implementation perspective. This blog has been adapted from Mr. Smith’s recorded presentation for the 8th International Symposium on Focused Ultrasound, held in October 2022.