12.01

2018
Breakthrough Immuno-oncology therapies – are they living up to the ‘hype’?
Written by Dr Niamh O’Reilly

 

Immuno-oncology therapies are increasingly being hailed as the fourth pillar of cancer treatment alongside surgery, chemotherapy and radiation therapy. Described as the ‘holy grail’ bringing about a ‘new era’ in cancer treatment, in the coming years a deluge of these therapies will move from the ideal treatment setting of clinical trials to enter the marketplace for use in clinical practice. One could argue that only then will we see beyond the ‘hype’ to more fully understand the potential of these therapies to impact patients’ lives.

Understanding immuno-oncology

Immunotherapies are designed to harness the natural tumour killing mechanisms of the patient’s immune system, thus improving the targeted killing of cancer cells. Unlike some other cancer drugs, these therapies tend to be suitable for only a sub-section of patients who can be identified using biomarkers. However, developing and manufacturing immuno-oncology therapies is costly and therefore the end products are expensive. For example, one recently approved checkpoint inhibitor priced at $51.79 USD per milligram can run over $1 million USD per patient per year.1 Another highly anticipated immune system activating therapy (CAR T-cell therapy) has been launched with a price tag of $475,000 USD per treatment.2 Healthcare systems worldwide are expected to fund these therapies but first they must understand the clinical benefits and cost effectiveness. In the case of cancer therapies this means seeking proof as to whether these therapies extend patients’ lives and/or improve their quality of life.

Investigating therapy value

These therapies have been developed following years of innovative research, yet they are often brought to market before there is sufficient evidence that they extend or improve patient’s quality of life. Overall survival remains the most compelling primary endpoint in oncology studies, however achieving this can take several years.3 In the case of potentially lifesaving therapies there is increased urgency and often the ‘hype’ puts pressure on governments to approve and fund these drugs by relying on surrogate endpoints.4 Of course, no payer wants to refuse to fund a drug due to the high cost and as yet uncertain clinical value only to find out the therapy could have saved many lives. However, the flipside is a potentially unfavourable benefit:risk ratio which does little to improve the patient’s prognosis.

Indeed, a recent study of oncology therapies approved by the European Medicines Agency (EMA) found that between 2009-2013 most oncology drugs entered the market without conclusive evidence of benefit to survival or quality of life.5 Furthermore, after a minimum of 3.3 years follow up, only 35 out of 68 cancer indications approved by the EMA had shown a survival or quality of life gain over existing treatments or placebo. For the remaining 33, uncertainty remains over whether the drugs extend survival or improve quality of life.

As oncology research continues to advance, more targeted and personalised therapies will become available and it will inevitably become increasingly difficult for governments to fund these therapies.6 Therefore, governments and payers may need to negotiate new funding mechanisms such as “conditional” funding deals.4 These deals require commitment from companies to provide post-marketing proof that their therapies are performing better than current treatment options and causing minimal toxicity while extending and/or improving patients’ quality of life. This could facilitate manageable funding of expensive therapies to ensure ongoing affordable access to those patients who will truly benefit.

CRC’s experienced Medical Affairs team are well equipped to demonstrate and communicate the value of innovative oncology therapies and develop effective engagement and market access strategies tailored to a client’s needs.

 

Definitions

CAR T-cell therapy:
Treatment that attempts to boost the natural ability of T-cells to fight cancer. T-cells are a type of white blood cell and part of the immune system. Researchers take T-cells from the tumour, isolate the T-cells that are most active against the patient’s cancer or modify the genes in them to make them better able to find and destroy cancer cells. Researchers then grow large batches of these T-cells in the lab and they are injected back into the patient.7

Check-point inhibitor therapy:
Therapy that blocks certain proteins made by specific types of immune cells such as T-cells and some cancer cells. These proteins help keep immune responses in check and can keep T-cells from killing cancer cells. When these proteins are blocked, the “brakes” on the immune system are released and T-cells are able to kill cancer cells better. Examples of checkpoint proteins found on T-cells or cancer cells include PD-1/PD-L1 and CTLA-4/B7-1/B7-2.8

Overall survival (OS):
The length of time from either the date of diagnosis or the start of treatment for a disease, such as cancer, that patients diagnosed with the disease are still alive. In a clinical trial, measuring the OS is one way to see how well a new treatment works. OS has long been regarded by the oncology community at large, as well as drug regulatory bodies such as the U.S. Food and Drug Administration (FDA), as the gold standard for demonstrating clinical benefit.9

Progression free survival:
The length of time during and after the treatment of a disease, such as cancer, that patient’s live with the disease without it getting worse. In a clinical trial, measuring the progression-free survival is one way to see how well a new treatment works.10

 

References

 

  1. Radio interview with Dr Leonard Saltz, Chief of Gastrointestinal Oncology at Memorial Sloan Kettering Cancer Centre. 2015. High Price of Cancer Treatment Drugs Is ‘Unsustainable,’ Doctor Says. Available at: https://www.npr.org/2015/06/01/411271175/high-price-of-cancer-treatment-drugs-is-unsustainable-doctor-says
  2. Mukherjee S., 2017. Is $475,000 Too High a Price for Novartis’s ‘Historic’ Cancer Gene Therapy? Fortune. Available at: http://fortune.com/2017/08/31/novartis-kymriah-car-t-cms-price/
  3. Available at: http://www.appliedclinicaltrialsonline.com/developing-new-clinical-endpoints-immuno-oncology-studies
  4. Cohen D., 2017. Cancer drugs: high price, uncertain value. The BMJ
  5. Davis C., et al, 2017. Availability of evidence of benefits on overall survival and quality of life of cancer drugs approved by European Medicines Agency: retrospective cohort study of drug approvals 2009-13. The BMJ
  6. Ward A. 2015. Healthcare: Counting the cost of cancer. Financial Times. Available at: https://www.ft.com/content/5e0b1f54-9ca0-11e4-a730-00144feabdc0
  7. National Cancer Institute. USA Department of Health. Immunotherapy to treat cancer. Available at: https://www.cancer.gov/aboutcancer/treatment/ types/immunotherapy
  8. National Cancer Institute. USA Department of Health. Immunotherapy to treat cancer Available at: https://www.cancer.gov/aboutcancer/treatment /types/immunotherapy
  9. National Cancer Institute. USA Department of Health. Immunotherapy to treat cancer Available at: https://www.cancer.gov/publications/dictionaries/cancerterms?cdrid=655245
  10. National Cancer Institute. USA Department of Health. Immunotherapy to treat cancer Available at: https://www.cancer.gov/publications/dictionaries/cancer-terms?cdrid=44782