Lenalidomide is an important medicine used for the treatment of multiple myeloma - a type of bone marrow cancer that is not curable and typically requires long-term, ongoing treatment. Lenalidomide, however, is perhaps most infamous for its high price tag.
The medicine has often been referred to as a "cash cow" in the media and has been highlighted in a report by the World Health Organization on problematic cancer medicine pricing strategies used by pharmaceutical companies. Lenalidomide's pricing in the United States has even been the subject of a congressional probe.
The most egregious case of price gauging for lenalidomide, however, may have occurred in South Africa when, in 2016, the cost of lenalidomide jumped by over a thousand percent overnight.
"That can't be possible," is what Salomé Meyer, organiser and advocate for the Cancer Alliance (a south African NGO), first said when she learnt of lenalidomide's massive price increase. In South Africa, price increases of registered medicines are strictly regulated and large increases for registered medicines are unheard of.
Meyer first heard about it by chance. While out walking her dog one evening, she bumped into the son of a friend undergoing treatment for multiple myeloma. He informed Meyer that the monthly cost of his mother's medicine, lenalidomide, had jumped from around R5 000 to over R70 000 per month. Like most people in South Africa, she was unable to afford lenalidomide at its new higher price.
Meyer immediately began investigating why the medicine's price had increased so much and what could be done to address it (disclosure: the author previously worked with Meyer in investigating cancer medicine price drivers, including for lenalidomide).
He informed Meyer that the monthly cost of his mother's medicine, lenalidomide, had jumped from around R5 000 to over R70 000 per month.
Meyer soon learnt that the culprit behind the price increase was, in fact, 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 in 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.
Sun Pharma bags USFDA okay for generic lenalidomide capsules @SunPharma_Live,@US_FDA #sunpharma #sunpharmanews #USFDA #lenalidomideCapsules #RevlimidCapsules #Celgene https://t.co/ovJLZDTifK
-- Medical Dialogues (@medicaldialogs) February 11, 2023
Before Revlimid was registered in South Africa, multiple myeloma patients in the country, with the assistance of their treating physicians, could use an avenue for importing unregistered drugs into the country - known as Section 21 authorisations - to import generic products. Using this avenue, 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 South Africa in 2016, Section 21 authorisations allowing importation of generic lenalidomide were halted and multiple myeloma patients learnt that they would now be required to use the far more expensive, branded product. In short, since there was now a registered product on the market in South Africa, the medicines regulator would no longer allow the importation of unregistered products using the Section 21 mechanism.
As an ongoing, long-term treatment, the cost of Revlimid was simply unaffordable for most. Even for those fortunate enough to have comprehensive private medical insurance, the annual cost of Revlimid typically exceeded what private medical schemes were willing to pay - leaving patients to foot a large portion, if not the bulk, of treatment costs.
For those seeking multiple myeloma treatment from the public sector, the important medicine was simply unmentioned and unavailable, with its price being considerably out of reach for the Department of Health.
After Revlimid was registered in South Africa, two separate processes began happening simultaneously to secure access to more affordable generic products unregistered in the country.
One process was legal, the other was not.
Both saved lives.
As an ongoing, long-term treatment, the cost of Revlimid was simply unaffordable for most. Even for those fortunate enough to have comprehensive private medical insurance, the annual cost of Revlimid typically exceeded what private medical schemes were willing to pay.
Using the legal system to facilitate access to generics
Meyer, together with clinical haematologist Dr Mike du Toit, connected with the law firm Webber Wentzel to discuss options to improve lenalidomide accessibility in early 2017. Weber Wentzel offered to provide pro-bono legal support to Meyer and du Toit in appealing the decision made by the then Medicine Control Council (MCC), which is now the South African Health Products Regulatory Authority (SAHPRA), to stop allowing the use of Section 21 authorisations for importation of generic lenalidomide following the registration of Revlimid.
At the current high price of lenalidomide (a cancer treatment) in South Africa, the gov't can't afford to buy it and the private sector is unwilling to cover its full cost. Options? Pay out of pocket, or go without. https://t.co/VWEWMlbVqB @FixPatentLaw #MyCancerYourProfits pic.twitter.com/bZU9Pip1CD
-- Initiative for Medicines, Access & Knowledge (@IMAKglobal) July 15, 2019
After multiple rounds of back and forth, the medicines regulatory authority agreed to allow the continuation of Section 21 authorisations for generic lenalidomide importation.
The catch, however, was that only patients who had accessed generic lenalidomide via Section 21 approvals prior to the registration of Revlimid could use this avenue to access generic products. For other patients, the much more expensive Revlimid was still the only option.
While limiting the use of 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 to access generics
As previously reported in the Mail&Guardian, the unaffordable price of Revlimid led some people in South Africa to use creative pathways to access more affordable versions of the medicine.
Through their own research and word-of-mouth information sharing, multiple myeloma patients quickly learned that generic lenalidomide could be bought in India for a fraction of the price charged for Revlimid in South Africa and that these medicines could sometimes be brought surreptitiously into the country by post or plane.
According to du Toit, one patient even went as far as importing lenalidomide's active pharmaceutical ingredient from India, which he then used to make pills for his personal use.
"It's extraordinary the lengths that patients will go to and the ingenuity that they will employ in terms of having the medication they are told or perceive they need," says du Toit.
For patients facing a life-threatening condition, circumventing legal pathways to access lenalidomide and using unregistered medicines was worth the risk.
While the resourcefulness of these patients is impressive, Meyer argues that 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," says Meyer.
Using patents to block generics
Lenalidomide has historically been an extremely profitable product for the pharmaceutical company Celgene and a key driver of its growth.
Lenalidomide is a derivative, or amended form, of the older medicine thalidomide, which was 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 in recent decades, 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 United States. 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 United States, multiple generic pharmaceutical companies seeking a slice of the lenalidomide market have challenged the validity of Celgene/BMS's patents on the drug. Several generic companies 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 are now facing a lawsuit in the U.S. 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 South Africa in 2016, the alliance identified two key barriers to the use of generics in the country - no generic lenalidomide products were yet registered in the country and patents applied for and granted in the country could prevent the marketing of generics even after they were registered.
When Celgene's Revlimid was registered in 2016, several generic companies had already submitted or were in the process of submitting applications for registration of its lenalidomide products. Cancer Alliance pursued its registration status with the MCC repeatedly, urging the regulatory authority to expedite its 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 that ongoing patent monopolies did not impede the use of generics following 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 South Africa and their dubious claims of inventiveness. The organisations called on government to issue a compulsory license (as done in Russia) to ensure that the patents would not block generic use following registration.
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In the end, Celgene/BMS, aware of the local and global advocacy underway around the medicine, did not take legal action to assert its patents to block the use of lenalidomide generics in South Africa following their registration.
A query sent to Cipla about whether the company has a marketing agreement in place with BMS related to the sale of lenalidomide in South Africa (as seen in other countries) was not answered by the time of publication.
Generic competition reduces cost
Following 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 is now sold for between R8 000 and R10 000 per month. Key Oncologics now sells 25mg Revlimid for R46 901 per month (excluding dispensing fees).
And, in the public sector, Cipla is now 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 that are not bought on tender.)
In the private sector, a month's supply of 25mg generic lenalidomide tablets is now sold for between R8 000 and R10 000 per month.
The low price offered to the public sector by Cipla has allowed for lenalidomide's inclusion on South Africa's essential medicines list (EML) - meaning that it should now be available to all patients that need the treatment. Although the updated EML indicates that thalidomide may continue to be used through 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 to Spotlight that, until the next tender is undertaken, "provinces and treatment centres can make the decision to buy out lenalidomide".
The updated EML says that lenalidomide should be used as a first-line treatment for multiple myeloma, in place of 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 to use, and it's more effective."
Disclosure: Tomlinson previously worked with the Cancer Alliance and served on the steering committee of the Fix the Patent Laws campaign. SECTION27 and the Treatment Action Campaign are members of the Fix the Patent Laws campaign. Spotlight is published by SECTION27 and the Treatment Action Campaign, but is editorially independent - an independence that the editors guard jealously. Spotlight is a member of the South African Press Council.
