Photofrin:  A Promising Drug with a Rocky History

Renee LeClerc

January 28, 2002

 

Julia Levy is a Canadian research Scientist with a vision to help cancer patients by improving chemotherapy drug delivery systems.  More than 20 years ago Dr. Levy became involved in the development of Photodynamic Therapy (PDT).  Photodynamic drugs are a group of drugs that can be injected into the body of a patient with cancer.  These drugs take advantage of angiogenesis (abnormal growth of blood vessels around malignant tumors) by concentrating in these areas of abnormal vessel growth.  Photodynamic drugs are able to cross the semi-permeable membranes of many types of cancer cells.  However, the drug is not activated until the tumor is exposed to the red light of a laser beam.  When the drug is activated free oxygen molecules (O2- instead of the commonly found O2) are created.  These charged oxygen molecules react within the cancer cells to cause cell death.

 

In 1981, Levy co-founded QTL Photodynamic Therapeutics Inc.  For 5 years Levy and her small team of researchers searched for a photodynamic drug therapy that could be produced for a reasonable price and be marketed within Canada.  Their efforts were unsuccessful until 1986,when Dr. Levy gave a talk in Waterloo, Ontario about the research being done at QTL.  It was at that conference that Dr. Levy met a group of disgruntled, and frustrated medical doctors.  They were talking about a new photodynamic drug known as Photofrin.  Photofrin (a photodynamic drug developed in the United States) was proving very successful in treating cancer patients before their disease had metastasized.  Unfortunately, Johnson & Johnson, the American

Biotechnology Company producing Photofrin had decided that it was not turning a profit fast enough and were going to shut the Photofrin research down. 

 

When Levy returned to her offices in Vancouver she called the executive of QTL together.  They discussed the fate of Photofrin.  It was decided that QTL would raise the hundreds of thousands of dollars needed to buy the rights to Photofrin from Johnson & Johnson.  In 1993, QTL’s gamble paid off and the Canadian government approved the use of Photofrin for the treatment of esophageal, bladder, cervical, stomach, skin and lung cancer.  The approval was a great triumph for the medical community but Photofrin, like many promising drugs, almost didn’t make it to market.  QTL was Photofrin’s last savior but it had experienced a very rough history.

 

Dr. Thomas Dougherty in Buffalo, New York through a sheer coincidence developed the forerunners of Photofrin, in 1972.  Dr. Dougherty had been searching for drugs that would produce oxygen in cancer cells.  He would test different drugs on cells in vitro and then stain them with a light activated stain to count the number of surviving cells. One day a research assistant advised him not to use a particular stain, as it would kill live cells when light activated.  This off handed suggestion gave Dr. Dougherty an idea. 

 

He began work on what would become known at Photofrin.  By 1978, Dr. Dougherty had carried out the first human trials of Photofrin on women with advanced breast cancer.  The cancer tumors responded very well to the drug but most of the patients died anyway due to the advanced nature of their disease.  He published a paper on his findings but was challenged by the FDA (Food and Drug Administration in the United States).  Dougherty had not applied to the FDA for approval to do his research.  The FDA demanded that Dougherty stop his trials and his research.  This was the first time that Photofrin looked as though is might die.

 

By early 1980 Dougherty had convinced the FDA that Photofrin was a promising drug and he was given a second chance.  He was required to redo his clinical/human trials again at great expense.  To fund the research he teamed up with Ciba-Geigy Biotechnology group.  When Ciba-Geigy discovered that they would not be able to patent the new drug (patents are a major way to make money in the biotech industry) they dropped Photofrin.  For the second time in less than 3 years it looked like the end for Photofrin.

 

Dougherty would not give up so easily.  He found a way to patent Photofrin under his own name.  He and a veterinarian colleague, who had been using Photofrin to treat animals with cancer, went to work producing the drug in an old liquor store.   The cost of producing the drug was enormous.  In 1983 Dougherty produced a second paper this time peeking the interest of Johnson & Johnson.  Johnson & Johnson supported the Photofrin research until 1986 when Linda Levy’s company again saved Photofrin from sure death and brought it to the world market.

 

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1) Photofrin experienced a very turbulent “life”, from the off-handed remark in Dr. Dougherty’s lab in 1972 to its approval, 22 years later, in Canada in 1993.  It spent most of its “life” struggling in the United States at the hands of the FDA and the big biotechnology firms there.  Do you believe that Photofrin would have taken the same amount of time (22 years) to get approved if it was discovered and researched in Canada?  Why or why not.

 

2) What would you have done if you were in Dr. Dougherty’s shoes?  Dr. Levy’s?  Would you do anything differently?

 

3) What would you do if you were the president of a huge biotechnology firm and a promising new drug therapy was not making its money back?  Would you risk losing your job to support a drug that could save thousands of lives but lose millions of dollars? Explain your reasons for the choice you would make.

 

4) We are familiar with the story of the apple falling on Newton’s head and the discovery of gravity.  We know that penicillin was accidentally discovered when mold contaminated a petri dish of bacteria in the lab of Alexander Fleming.  Now we have learned that Photofrin was “born” from an offhanded remark made to Thomas Dougherty.  Do you think that many scientific discoveries are made from these types of coincidental events?  Why or why not.

 

 

Curriculum Fit:  Biology 30 - Unit 3:  Cells, Chromosomes and DNA

                                                Topic 1:  purpose of cell division before reproduction

                                                -this story can be used to discuss the STS connection for                                                      understanding cell division as starting point to cancer                                                          research

 

Resources

 

Author unknown (Feb. 1999).  1999 honorary degree recipient.  Simon Fraser News, 14(3)

 

Cauchon, D.  (November 24, 1999).  High price, high hopes for cancer drug.  USA Today.

 

Conacher, D. (1999).  More Canada Firsts.  Toronto:  M&S.

 

The Governor General of Canada.  Order of Canada:  Julia Levy, Retrieved January, 2002, from http://www.gg.ca/cgi-bin/oc_details.pl?lang=e&rec_id=7080

 

Inventive Women (2000).  Dr. Julia Levy, Retrieved January, 2002, from http://inventivewomen.com/library/library_julialevy_bc.html

 

Science.ca.  Julia Levy.  Retrieved January, 2002, from http://www.science.ca/scientists/scientistprofile.php?pID=12

 

Shell, B.  (1997).  Great Canadian Scientists.  Victoria, B.C.:  Polestar Book Publisher.

 

Williams, L.  Into the Light:  The Story of One drug and America’s Drug Approval Process.  Retrieved January, 2002, from http://www.kip.jcomm.ohio-state.edu/into_the_light.htm

 

Yount, L. (1999).  A to Z of Women in Science and Math.  New York, NY:  Facts on File.