Cash money: US cures hopeless cases of cancer

The history of the emergence of CAR-T clearly illustrates how scientific progress goes and what personal factors drive it. CAR-T therapy owes its appearance to the many hundreds of scientists who have worked for many decades.

The idea of ​​using the immune system in the fight against cancer dates back to the 19th century, when in 1891, an American surgeon William Coley introduced specially developed bacteria cultures to several patients with inoperable tumors, which led to an immune response and a reduction in the size of tumors. Kohl's works were ignored, and he himself was proclaimed a charlatan. It took 102 of the year to create the first line of genetically modified T cells in Israel in 1993. In the USA, the scientist Carl Joon was engaged in the possibilities of T-cell modification exclusively in the framework of basic research. But in 1996, ovarian cancer was discovered in his 41-year-old wife. Karl tried to develop a medicine for his wife, but did not have time. Carl Juna's wife passed away in 2001. In those years, it was extremely difficult to attract funding for such projects — in 1999, there was an infamous death of a relatively healthy 18-year-old volunteer patient as a result of gene therapy. After the procedure, his kidneys, lungs and brain simultaneously failed.

For a decade, Carl June led the development within the research institute and, according to him, was not once ready to surrender. The climax was the rescue of the first patient, Emily Whitehead, in 2011. According to Juna, if Emily had died, the entire CAR-T direction would have gone into oblivion with her. Emily Whitehead also experienced severe side effects - a multi-day fever, the so-called "cytokine storm." Patients can be on the verge of life and death for about a week, but already now there is an understanding of how this condition can be controlled. In a clinical study conducted by the company Novartis using Karl Joon's technology, this typical response to the introduction of CAR-T cells was experienced in the order of 78% of patients, but thanks to the developed complex of therapeutic countermeasures, the drug Kymriah received unanimous approval of FDA experts and was admitted to clinical practice.

It becomes obvious that the direction will take a worthy place in the line of existing methods of influencing cancer processes: hormone therapy, targeted chemotherapy and immunotherapy.

Therapy CAR—T: the price of healing

After the approval of the first gene therapy based on the CAR-T technology, the main topic of discussion was the price. The old model of the pharmaceutical business in the field of oncology suggested long courses of drugs for a wide range of patients for many years or for life. Gene therapy methods, as a rule, are directed to very narrow groups of patients and are used once. Therefore, it becomes difficult for pharmaceutical companies to return their investments. Obviously, in connection with the change of treatment paradigm, a new pricing model and optimization of production and logistics technologies are required.

Recently, the company Novartis announced a price - $ 475 000 for one procedure. The price was significantly lower than expected (in Europe, the first approved gene therapy costs more than $ 1 million per patient), but, of course, could not avoid criticism. According to the representative Novartis, approaches to pricing, based on clinical value, confirm that the price of $ 600 000-750 000 is cost-effective for the state, because alternative therapies in children - bone marrow or stem cell transplantation - collectively leads to costs reaching $ 800 000 in the first year of treatment.

As a result, Novartis proposed a simple solution: for all patients who are covered by state insurance, the company will receive full payment for the procedure only if it is successful. In addition, representatives of the company assure that they are working on special programs of access to treatment for patients without state insurance. As far as the market is ready to introduce a new procedure, it is not yet obvious that the industry is awaiting sales figures in the first quarters. According to analysts, the sales volume could reach a peak of up to $ 2 billion in the US market or about 4 000 patients per year.

How much did CAR-T technology investors earn?

Simultaneously with the approval of the first gene therapy in the USA, one of the largest pharmaceutical companies Gilead with a market capitalization of over $ 100 billion announced the acquisition of the company KITE Pharma with technology CAR-T for $ 11,9 billion drug approval KITE Pharma expected in the coming months. Gilead agreed to buy the company at a price of $ 180 per share with a relatively modest premium to the market at 29%, but it is worth noting that just 3 a year ago the company's IPO in the amount of $ 128 million was considered exceptionally successful at a price of 10 $ 17. Accordingly, for participants in an IPO who waited for a successful exit, the return on investment was more than 100% per annum.

But the largest sole beneficiary was the CEO of the company Ari Belldegran. He is currently working as a professor at the University of California and, according to The Hollywood Reporter, is one of the best urologists in Hollywood. In parallel with clinical practice, he founded a number of companies, including those with successful exits.

Real estate sales KITE Pharma brought Professor Belldegran about $ 700 million as the largest shareholder and head of the company. According to the latest estimates of Forbes Israel (before the transaction), his fortune was already estimated at $ 1 billion. Belldegran will share success with his colleagues, for example, the company's chief operating officer Cynthia Buttita will receive $ 120 million, and as a result R & D company The deal will receive about $ 100 million.

In total now about 40 biotech companies are engaged in developments in the field of CAR-T. Of these, three leading companies: KITE, Juno and Novartis, and new players add heat to the competition.

Фото: Depositphotos

Beginning of the digital medicine era

Genetic engineering and the "management" of the genome are gradually becoming the mainstream of high-tech medicine. It is curious, however, to note that the Nobel Committee, contrary to expectations, this year did not award the prize to scientists for the sensational technology of editing the genome Crispr, and noted their colleagues, who investigated molecular mechanisms biological rhythms. Indeed, after many years of research, scientists are increasingly inclined to believe that the most common ailments can be adjusted precisely by a healthy lifestyle.

So at the beginning of this year, the book was published in collaboration with Elizabeth Blackburn, the Nobel winner of 2009 of the year, who discovered telomerase and the role of telomeres as a “biological clock of aging”. The book is called “The effect of telomeres: a revolutionary approach to the extension of youth, health and life” (The Telomere Effect: A Revolutionary Approach to Living Younger, Healthier, Longer). Many readers expected new discoveries in the field of molecular biology and stories about anti-aging “genetic” injections. In the book, the scientist quickly moves from the discussion of telomerase to practical recommendations for extending life: quality sleep, exercise and a healthy diet. She also recommends driving away negative emotions and unpleasant neighborhoods. It is hard not to agree with these tips of the Nobel laureate.

In connection with these "discoveries" in the world began to develop thousands of convenient applications to track the state of the body. But they all took place in the category “improving overall well-being” (wellness), prices were minimal and typical for mobile applications. In this form, this sector was not of interest to the pharmaceutical market. In 2015, the development of digital medicine was supported by the US Government Food and Drug Administration (FDA). The regulator has released a new instruction on medical mobile applications, which allowed start-ups to enter multi-billion dollar markets, including public and private insurance. Since then, it has become possible to prove the clinical value of mobile applications and receive reimbursement for them from insurance companies. Thanks to this support, the market volume has grown significantly. This year a record will be set in terms of the volume of venture capital investments in the Digital Health - estimated by the management company Rock health, investment in the first three quarters has already exceeded $ 4,7 billion.

14 September of this year in the United States was approved the first mobile application Reset for clinical reasons. The application aims to combat the disorder caused by the use of psychoactive substances: alcohol, cocaine, marijuana and others. As part of a clinical study, it was reliably shown that the use of the application increased the ability of patients to refrain from using substances in 40.3% cases against 17.6% with current standards of treatment. This application will be “downloaded” exclusively by prescription.

We discussed the prospects of this area with a member of our advisory board Edom Godber, a top manager in the past. GlaxoSmithKline And company PatientsLikeMe, one of the most successful projects in the field Digital Health. In his opinion, approval Reset opens a new page in the field of medicine. Digital medicine can potentially be applied to the largest therapeutic areas: type 2 diabetes, obesity, hypertension, attention deficit hyperactivity disorder, depression, and even Alzheimer's disease. All these diseases are associated with our behavior and lifestyle and form multi-billion markets, where today there are often ineffective drugs.

Thus, this year new records are expected to be set in terms of investment in Life Sciences and Digital Health USA. This is due to the fact that gene therapy, RNA interference, digital medicine and many other technologies reach the stage of maturity and open up new horizons for curing previously hopeless cases of cancer and genetically caused diseases, as well as for preventing and combating chronic illnesses.