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Results through competitive collaboration: Breakthrough in Gene Therapy

By  |  September 1, 2017, 03:08pm


Proverbs 24:5 (ESV): A wise man is full of strength, and a man of knowledge enhances his might.

August 30, 2017, will be held in high regard for decades to come, as on this day two major pharmaceutical companies, Novartis, and Roche, distributed independent public announcements after years of competitive collaboration. Indeed, capitalistic competition has led to a stupendous breakthrough treatment for certain pediatric and young adult patients with a form of acute lymphoblastic leukemia (ALL). Plus, breakthrough treatment will be available for these patients if they develop a dangerous side effect, namely Cytokine Release Syndrome (CRS). ALL is a cancer of the bone marrow and blood where the body makes abnormal lymphocytes, and CRS is a serious side effect as a response to the necessary treatment of ALL, causing high fever and flu-like symptoms.

The FDA approved Kymriah (tisagenlecleucel) from Novartis, and Actemra (tocilizumab) from Roche, to treat ALL and CRS, respectively. Kymriah is a humanized CD19-directed chimeric antigen receptor T cell (CAR-T) cell therapy. This is different than small molecule or biologic therapies, as this treatment is, truly, personalized medicine. The treatment is manufactured for each patient, individually, using his or her own cells. The process takes T cells from the patient and is reprogrammed in the laboratory to create a type of fighter-target T cell that hunts the patient’s cancer cells. A side effect of this T cell re-entry is activation and proliferation of CAR-T cells; this is the definition of CRS. Administration of Actemra to treat CAR-T-cell-induced CRS results in complete resolution of the side effect within two weeks, after only one or two doses of Actemra. Fantastic!

These approvals mark the first time in FDA and US history that gene therapy has been approved and made available in the United States.

The story of this competitive collaboration is filled with frustration and glory, flat-out perseverance and focused-agility. In 2012, the Pharma world noticed Emma Whitehead.

Novartis and the Children’s Hospital of Philadelphia (CHOP) had collaborated to provide an experimental treatment for her leukemia. She suffered from CRS, which nearly killed her (shock and multi-organ failure). Another experimental treatment was given to Emma to treat the CRS.  She survived and thrived!

Fast-forward; in 2014 Roche personnel were in discussions with the FDA about Actemra, based on data generated by Novartis and Kite Pharmaceuticals, both working on CAR T-cell therapies. The FDA based the approval of Actemra on pooled efficacy analysis data from the clinical trials of Novartis and Kite Pharmaceuticals. Both companies used Actemra to treat patients presenting with CRS. In the ensuing years, up to the announcement, collaboration among the pharmaceutical companies and the FDA lead to successful regulatory submission filings.

“Kymriah is a first-of-its-kind treatment approach that fills an important unmet need for children and young adults with this serious disease,” said Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research (CBER). “Not only does Kymriah provide these patients with a new treatment option where very limited options existed, but a treatment option that has shown promising remission and survival rates in clinical trials.”

Dr. Carl June at University of Pennsylvania, who pioneered CAR T-cell therapy for the treatment of acute leukemia, noted that Actemra saved Emma’s life: “It was literally one of those Lazarus conditions….”

Congratulations to the hundreds of people taking part to make this milestone a reality. Laboratory research and clinical teams, hospital personnel, patients willing to participate in clinical trials, regulatory personnel, and a multitude of other key persons are precise examples of collaboration.

God Bless to All!