Brave New Therapeutics: The Virus that Cures, the Drug that Lives
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During the summer of 2006, I was witness to a rare sight one sunny New York Sunday afternoon. A long stretch of 8th Avenue was shut off in midtown Manhattan due to the filming of Will Smith’s next sci-fi epic. “I Am Legend” would open almost 18 month later and achieve blockbuster status for Warner Bros. both in the US and International Box Office.
The film begins with a clip of Dr. Alice Krippin who genetically engineers the measles virus as a cure for cancer. This Krippin Virus, or KV, at first appears to be effective with no side-effects, but over time, the virus starts to mutate, turning its mamalian hosts into rabid zombie-like dark seekers.
The Virus That Cures
Last week, a startup called Homology Medicines raised an impressive $127 million by claiming to treat genetic diseases using viruses that efficiently repairing human genes, all on their own.
Indeed, the past few years have been a boon for startups focused on CRISPR/Cas 9 gene editing or what is also commonly known as Gene Therapy 2.0. CRISPRS has frequently be likened to simply cutting and pasting DNA like scissors. The scissors in this case are nucleases; protein enzymes that are capable of cleaving that pesky phosphodiester bond between monomers of nucleic acids, where we are concerned, of the deoxyribo variety.
Homology however, plans to edit genes without adding a nuclease, and therefore without breaking the continuity of the DNA strand, which typically increases the chances of toxicity. Instead, the DNA is delivered by a viral vector that closely matches a homologous gene (hence the name Homology), thus essential performing the surgery without a scalpel.
Now before we start getting all Hollywood, it is important to mention that the seventeen patented viruses currently experimented on at Homology Medicines are what are known as adeno-associated viruses (AAVs). These small viruses can easily infect humans as well as some other primate species and are usually quite targeted in that some may even infect specific organs. Think of them as non-lethal smart bombs since AAVs are not currently known to cause any actual diseases in their hosts with their virility limited to a very mild immune response, which lends further support to their apparent lack of pathogenicity.
In fact, the ultimate Holy Grail of personalized or precision medicine would be to combine the power of CRISPR with the simplicity of these relatively newer gene-therapy methods, whereby the editing could be efficiently carried off with only a homologous AAV via a simple single injections into the body.
The Living Drug
Shifting from the lab and onto the prescription pad, last week also so a “historic action” when the US FDA approved a new drug, Kymriah, as a landmark cancer drug that uses genetically modified immune cells from patients to attack their own cancer.
Kymriah is the world’s first “living drug” since the treatment (also known as CAR-T cell therapy) involves removing T cells from the patient immune system and then genetically modifying the cells in the laboratory to attack and kill leukemia cells.
The historic approval bodes well for rival companies Kite Pharma and Juno Therapeutics, which are also developing CAR-T therapies. Kite Pharma, which is awaiting FDA approval for its CAR-T therapy to treat a form of blood cancer in adults, was also last week bought out by Gilead in a record deal worth $11.9 billion.
Kymriah (which to me sounds like a portmanteau of Kim and Mariah) is now approved to treat children and young adults up to age 25 that suffer from a form of Acute Lymphoblastic Leukemia (ALL) who typically do not respond to standard treatment or have suffered relapses. ALL is the most common blood and bone marrow childhood cancer in the United States, with just over 3,000 patients who are 20 and younger diagnosed each year according to the National Cancer Institute. Current treatment options include chemotherapy and stem-cell transplants, but about 600 pediatric and young adult patients with the disease relapse each year, and many remain incurable.
Thankfully, during clinical trials Kymriah produced remission within three months in 83% of the 63 pediatric and young adult patients who had failed to respond to standard treatments or had suffered relapses. At six months, 89% of patients who received the therapy were still living, and at 12 months, 79% had survived. The treatment does carry risks, however, including a dangerous overreaction by the immune system known as cytokine-release syndrome. As a result, the FDA is requiring strong warnings. In addition, the treatment will be initially available only at 32 hospitals and clinics that have been specially trained in administering the therapy.
With innovation in therapeutics, so too comes innovation in pricing. Novartis, which developed Kymriah, has priced the one-time treatment at $475,000 per positive response. This means that patients who do not respond to Kymriah within a month would not be charged. To its credit, Novartis is also taking additional steps to make sure everyone who needs the drug can afford it.
My innovative funding mechanism? Perhaps Novartis could partner with Warner Bros. to produce I Am Legend II and I Am Legend III, since the first version of the film grossed a cool $585 million world wide almost a decade ago (today thats equal to around $680 million) which neatly covers about half of all ALL patients in the USA. We would naturally need a trilogy to cover all 3000 plus patients plus satisfy our intense love of the Fresh Prince.
