Biosimilar Breast Cancer Drug Gets WHO Seal Of Approval – Agency Aims To Increase Worldwide Access To Life-Saving Treatment

The World Health Organization (WHO) has given its quality seal of approval to a biologically similar formulation of the breast cancer drug  – trastuzumab – in a move the agency says could help make the costly, life-saving treatment more affordable and available to women globally.

Breast cancer is the most common form of cancer in women. Some 2.1 million women contracted breast cancer in 2018. 630,000 of them died from the disease, many because of late diagnosis and lack of access to affordable treatment, WHO said in a press release announcing the move.

Trastuzumab – a monoclonal antibody – was included in the WHO Essential Medicines List in 2015 as an essential treatment for the estimated 20% of breast cancer tumors that test positive for the protein human epidermal growth factor receptor 2 (HER2), which promotes the growth of cancer cells. In such tumors, the drug has shown high efficacy in curing early stage breast cancer and in some cases more advanced forms of the disease, WHO says.

Trastuzumab, which was originally produced under the brand name Herceptin® by Roche Pharmaceuticals, is among a number of biotherapeutics, or pharmaceutical products, derived from biological and living sources, which have become increasingly important in cancer treatment. “Biosimilar” formulations of biological health products are the equivalent of generic formulations of synthetic drugs.

Cancer patient received a drug infusion

The newly pre-qualified product is produced by the Dutch-based firm Samsung Bioepis; it was the first is the first trastuzumab product to be assessed by WHO and found comparable to the originator product in terms of efficacy, safety and quality, the global health agency said.

The WHO Prequalification process is a seal of good quality that makes a drug company’s product eligible for bulk procurement by United Nations agencies. But in the case of drugs for cancer and other non-communicable diseases, there are almost no UN-based donor programmes for procurement and supply to low-income countries.

Even so, the WHO label will signal to national governments that the product is quality-approved by WHO. Such a signal can eventually help pave the way for more bulk purchases of  cheaper, but quality-approved biosimilar cancer drugs by national health systems, thereby reducing prices, said a WHO scientist in an interview with Health Policy Watch.

“Historically, the WHO Prequalifiation process was used to pave the way for procurement of products for HIV, TB and malaria [by donors and UN agencies]. Then, it was expanded to some reproductive health drugs and to diagnostic devices, and then to drugs for other neglected diseases.  Now, cancer has become part of the process.  Although we don’t have a big procurement of cancer drugs from a UN agency, this signals that cancer treatment is an integral part of Universal Health Coverage, and should be part of a national benefits package,” the scientist said.

Integration of such drugs into the WHO Prequalification process could help drive down costs of treatment by about 60-70% of the prevailing prices: “but lets see how the market reacts,” the scientist said. Currently, annual treatment costs for the brand name product range from about US$ 10,000 in South Africa to about US$ 19,000 in Australia and US $29,000 in the USA, according to an informal WHO survey of published consumer list prices in the marketplace.  Biosimilars sold in India and Italy cost around US$ 4,000.

“WHO prequalification of biosimilar trastuzumab is good news for women everywhere,” says Dr Tedros Adhanom Ghebreyesus, WHO Director-General in the press release. “Women in many cultures suffer from gender disparity when it comes to accessing health services. In poor countries, there is the added burden of a lack of access to treatment for many, and the high cost of medicines. Effective, affordable breast cancer treatment should be a right for all women, not the privilege of a few.”

Biotherapeutic medicines, which are produced from biological sources such as cells rather than synthesized chemicals, are important treatments for some cancers and other non-communicable diseases. Like generic medicines, biosimilars can be much less expensive versions of innovator biotherapeutics while keeping the same effectiveness. They are usually manufactured by other companies once the patent on the original product has expired.

WHO’s International Agency for Research on Cancer estimates that by 2040 the number of diagnosed breast cancers will reach 3.1 million, with the greatest increase in low- and middle-income countries.

A recent study of breast cancer in sub-Saharan Africa found that of 1325 women surveyed in three countries, cancer treatment had not been initiated within one year of diagnosis for 227 (17%) women and for 185 (14%) women with stage I-III disease. Self-reported treatment barriers confirmed treatment costs as a major contributor to not receiving treatment.

“We need to act now and try to avoid more preventable deaths,” said Mariângela Simão, WHO Assistant Director General for Medicines and Health Products. “The availability of biosimilars has decreased prices, making even innovative treatments more affordable and hopefully available to more people.”

James Love of Knowledge Ecology International, which has advocated for reducing cancer drug prices as an important element of increasing drug access, welcomed the WHO move but said that more needed to be done to fund the WHO Prequalification process more fully so that it could conduct more such reviews, and more rapidly.

“The PreQual process has always been very important to patients, particularly those living in countries with limited capacity to provide safety and efficacy regulation,” Love said in a statement to Health Policy Watch. “The limitations on this process have largely been financial, finding donors or other ways to pay for the necessary reviews. It’s a stain on the WHO and its members that the agency has never been able to marshal the resources that are needed to expand the program into the many areas where it is needed, and certainly drugs for cancer and biologic drugs are among those areas where PQ is really needed.  The Samsung trastuzmab decision is a welcome step, and one hopes that someday the WHO will have the resources to do what is needed.”

However reducing the price of cancer drugs such as trastuzumab will not, alone, ensure that women get cancer treatment in low or even middle income countries, WHO officials also stress. Use of the drug firstly requires a well functioning health system that can provide early diagnosis of cancer tumors, followed by appropriate surgery, chemotherapy and/or radiation treatment, as preconditions for optimal use of biological drug therapies.

“It’s not a test and treat pill,” underlined the WHO scientist in the Health Policy Watch interview. “Its part of a combined regimen, and fairly complex. These are not easy drugs to delvier, and the largest gains are generally for women with early diagnosed breast cancer of HER2+.   Still, this signals how WHO is trying to project cancer drugs as something for which we should increase the uptake.

Gene-based therapies such as CAR-T are among the other new biologic “specialty treatments” that have been developed to treat other rare forms of cancer, and currently they come with even higher price tags attached.  Examples of other biotherapeutics products, include therapeutic vaccines, blood, blood components, cells, gene therapies, tissues and other materials. They are used to treat chronic diseases such as diabetes, Crohn’s disease and other autoimmune conditions, including lupus, and various forms of rheumatoid arthritis.

WHO Prequalification is a service provided by the agency to assess the quality, safety and efficacy of products that address global public health priorities. Products that receive WHO’s seal, are then listed on the Prequalification web site as eligible for procurement, giving purchasing agencies a range of quality-assured diagnostics, medicines and vaccines from which to choose. Every year, billions of dollars’ worth of medicines and other health products are purchased by international procurement agencies for distribution in low-income countries, based on WHO recommendations. Many low-income countries also use WHO’s lists of prequalified products to guide their selection of medicines, vaccines and technologies for national procurement.

In July 2018, WHO launched a pilot project expanding the scope of prequalification to two biotherapeutic medicines, including rituximab used to treat certain leukemias and lymphomas, along with trastuzumab, as a step towards making some of the most expensive treatments for cancer more widely available in low- and middle-income countries. About six other companies have begun producting trastuzumab over the past five years, driving down prices of the original product, but the Dutch product is the first to be prequalified as part of the pilot.

Image Credits: Linda Bartlett/National Cancer Institute.