Lenalidomide is an important medicine in the treatment of multiple myeloma but it’s probably most infamous for its high price tag, notes MedicalBrief.
So high is the cost for the drug, that it has been the subject of a congressional probe in the US and, now, has been highlighted in a report by the World Health Organisation on problematic cancer medicine pricing strategies used by pharmaceutical companies.
The most egregious case of price gauging for lenalidomide, however, may have occurred in South Africa when, in 2016, the cost jumped by more than 1 000% percent overnight, writes Catherine Tomlinson in Spotlight.
“That’s impossible,” is what Salomé Meyer, organiser and advocate for the NGO Cancer Alliance first said when she heard about the massive increase.
She’d heard about it by chance, through the son of a friend undergoing treatment for multiple myeloma: he said his mother’s medicine, lenalidomide, had jumped from around R5 000 to more than R70 000 per month. She was unable to afford the new price.
Meyer immediately began investigating. She learned that the reason for the increase was the registration of Celgene’s (now wholly owned by Bristol Myers Squibb [BMS]) branded lenalidomide product, Revlimid, in South Africa.
Revlimid, which had already attracted attention globally for its excessive pricing, was introduced to South Africa by Key Oncologics in 2016 at a list price of R73 500 for a month’s supply of 25mg tablets, or R882 000 per year.
Before Revlimid was registered in SA, multiple myeloma patients here, with the assistance of their treating physicians, could use an avenue for importing unregistered drugs into the country – known as Section 21 authorisations – for bringing in generic products.
This way, multiple myeloma patients had been importing generic lenalidomide for a fraction of the price charged by Key Oncologics for Revlimid.
But when Revlimid was registered in SA in 2016, Section 21 authorisations allowing importation of generic lenalidomide were halted and myeloma patients discovered they would now have to use the far more expensive, branded product. And, since there was now a registered product available on the market, the medicines regulator would no longer allow the importation of unregistered products using the Section 21 mechanism.
As an ongoing, long-term treatment, Revlimid’s cost was unaffordable for most. Even for those with comprehensive private medical insurance, Revlimid’s annual cost typically exceeded what private medical schemes would pay – leaving patients footing a large portion, if not the bulk, of treatment costs.
For those seeking multiple myeloma treatment from the public sector, the important medicine was unmentioned and unavailable, the price being considerably out of reach for the Department of Health.
After Revlimid was registered here, two separate processes began happening simultaneously to secure access to more affordable generic products unregistered in the country. One process was legal, the other not. Both saved lives.
Legal system to facilitate access to generics
Meyer and clinical haematologist Dr Mike du Toit contacted legal firm Webber Wentzel to discuss options to improve lenalidomide accessibility in early 2017. Weber Wentzel offered to provide pro-bono legal support to them in appealing the decision by the then Medicine Control Council (MCC), now the South African Health Products Regulatory Authority (Sahpra), to prohibit Section 21 authorisations for importation of generic lenalidomide after the registration of Revlimid.
After multiple rounds of back and forth, the regulatory authority agreed to allow the continuation of Section 21 authorisations for generic lenalidomide importation.
The catch was that only patients who had accessed generic lenalidomide via Section 21 approvals before the registration of Revlimid could use this avenue to access generic products. For other patients, the pricier Revlimid was still the only option.
While limiting Section 21 authorisations to formerly treated patients was disappointing to Meyer and Du Toit, the MCC’s decision enabled patients formerly treated with generic lenalidomide to remain on treatment. It also strengthened the existing precedent that the registration of a branded medicine should not interrupt the use of generic products via Section 21 approvals when branded medicine is priced out of reach for those already using generics.
Alternative avenues pursued for generics
The unaffordability of Revlimid led some South Africans to use creative pathways to get more affordable versions of the medicine.
Through their own research and word-of-mouth, they quickly learned that generic lenalidomide could be bought in India for a fraction of the price charged for Revlimid in SA, and could sometimes be brought surreptitiously into the country by post or plane.
Du Toit said one patient even imported lenalidomide’s active pharmaceutical ingredient from India, which he then used to make pills for his personal use.
While their resourcefulness is impressive, Meyer said they should never have been forced to take such risks (both the legal risks and the health risks associated with taking a medicine not yet determined to be safe by Sahpra) to access affordable prices for lenalidomide. “The cost of manufacturing lenalidomide is minuscule,” Meyer says.
Using patents to block generics
Lenalidomide has historically been an extremely profitable product for pharmaceutical company Celgene and a key driver of its growth.
It’s a derivative of the older medicine thalidomide, first marketed in the 1950s. While thalidomide has a dark history of resulting in severe birth defects when marketed to pregnant women during the 1950s and 1960s, the medicine’s reputation has been rehabilitated, with its effectiveness in treating multiple myeloma becoming apparent.
To secure and extend its monopoly over lenalidomide, Celgene has pursued a “thicket” of patents around multiple aspects of the medicine and its uses. In 2017, I-MAK, a public interest organisation seeking to address drivers of inequity in the patent system, identified 76 pending and granted patents pursued by Celgene on lenalidomide in the US.
In South Africa, the Cancer Alliance has identified 32 patent applications filed by Celgene on lenalidomide.
Celgene was bought by Bristol Meyers Squibb (BMS) in 2019, which also acquired the company’s patents.
In the US, multiple generic pharmaceutical companies seeking a slice of the lenalidomide market have challenged the validity of Celgene/BMS’s patents on the drug. Several later dropped their patent challenges after signing “pay-for-delay” agreements with Celgene/BMS, which delayed the introduction of generics or allowed for limited-volume introductions.
BMS, Celgene and multiple generic companies now face a lawsuit in the US charging them with anti-competitive practices that undermined generic lenalidomide competition in the country.
Advocating for generic access
When the Cancer Alliance started working on improving access to affordable lenalidomide in SA in 2016, it identified two key barriers: no generic lenalidomide products were yet registered here, and patents applied for and granted in the country could prevent the marketing of generics even after registration.
When Celgene’s Revlimid was registered in 2016, several generic companies had already submitted or were submitting applications for registration of its lenalidomide products. Cancer Alliance pursued its registration status with the MCC repeatedly, urging the regulatory authority to expedite authorisation.
In 2020, five generic companies received authorisation to market their generic lenalidomide products in South Africa: Cipla, Adcock, Forrester, Dr Reddy’s and Eurolab.
To ensure ongoing patent monopolies did not impede the use of generics after registration, the Cancer Alliance and member groups of the Fix the Patent Laws campaign spent several years raising awareness about the problematic patents granted on lenalidomide in SA and their dubious claims of inventiveness. The organisations called on government to issue a compulsory licence (as done in Russia) to ensure the patents would not block generic use after registration.
In the end, Celgene/BMS, aware of the local and global advocacy around the medicine, took no legal action to assert its patents to block lenalidomide generic use in South Africa after registration.
A query to Cipla about whether the company has a marketing agreement in place with BMS related to lenalidomide sales in SA (as seen in other countries) was not answered by the time of publication.
Generic competition reduces cost
After the registration of generics in 2020, competition ushered in substantially reduced prices. In the private sector, a month’s supply of 25mg generic lenalidomide tablets now costs between R8 000 and R10 000 per month. Key Oncologics sells 25mg Revlimid for R46 901 per month (excluding dispensing fees).
And, in the public sector, Cipla is selling 25mg lenalidomide at a buy-out price of R1 150 per month. (A buy-out price refers to a price quoted and offered to the public sector for medicines bought on tender.)
The low price offered to the public sector by Cipla has allowed for lenalidomide’s inclusion on SA’s essential medicines list (EML) – meaning it should now be available to all patients needing it. The updated EML indicates thalidomide may still be used until July 2024 as it will continue to be procured under the current tender.
Khadija Jamaloodien, director of the National Department of Health’s Affordable Medicines Unit, however, clarified that, until the next tender is undertaken, “provinces and treatment centres can make the decision to buy out lenalidomide”.
The updated EML says should be used as a first-line treatment for multiple myeloma, replacing the older product thalidomide.
“Lenalidomide is more effective against myeloma than thalidomide,” Du Toit told Spotlight. “It has the same side-effects, but they’re not as prevalent. So, it’s easier to use, it’s safer, and more effective.”
See more from MedicalBriefs archives:
Plea for SA to approve generic of costly cancer drug Revlimid
Registration of Cipla’s landmark oncology drug
NGOs want drug pricing transparency, slate govt over ‘pharma friendly’ policies
SA cancer rates set to double by 2030, actuaries predict
MSD: The lifesaving case for reforming South Africa’s medicine laws