Estimated generic prices of cancer medicines deemed cost-ineffective in England: a cost estimation analysis

The recommended dose of imatinib is 400 mg/day for the adjuvant treatment of adult patients following resection of GIST. Length of treatment in the clinical trial supporting this indication was 36 months (see section 5.1). Using published figures of the epidemiology of cancers for which the chosen medicines are indicated, we estimated the annual volume of demand in terms of tonnes of API that would be required to treat all incident cases. We estimated the incidence of all cancers for which the four chosen drugs are indicated, including multiple myeloma, chronic myeloid leukaemia, acute lymphoblastic leukaemia, renal cell carcinoma and non-small cell lung cancer.

Patent coverage and global prices

When female rats were dosed 14 days prior to mating and through to gestational day 6, there was no effect on mating or on number of pregnant females. At a dose of 60 mg/kg, female rats had significant post-implantation foetal loss and a reduced number of live foetuses. • adult patients with unresectable dermatofibrosarcoma protuberans (DFSP) and adult patients with recurrent and/or metastatic DFSP who are not eligible for surgery. • the treatment of adult patients with Kit (CD117)-positive unresectable and/or metastatic malignant gastrointestinal stromal tumours (GIST).

Imatinib for the treatment of unresectable and/or metastatic gastro-intestinal stromal tumours

This sparked a nationwide conversation on cancer drug prices and value. Switching from the branded form of imatinib (Glivec, Gleevec in the USA, Novartis) to a generic version to manage chronic myeloid leukaemia (CML) can lead to huge cost savings without compromising patient outcomes or safety, the results of a UK analysis suggest. One example is imatinib (Gleevec, Novartis), used for the treatment of chronic myeloid leukemia (CML). At present, the cost per 400-mg tablet is $0.22 in India; the cost-based generic estimate that Barber and colleagues calculated is $1.04. This contrasts with current price per tablet of $57.53 in Spain, $84.36 in the United Kingdom, and $247.74 in the United States (at Veterans Affairs prices, which are discounted).

• The lowest available generic price globally was £688.96 per month, assuming off-label use, and £851.65 on-label, for Indian products (figure 6).
• While this price is significantly below than that in other countries (figure 7), it is ninefold the estimated generic price of £10 per month.
• As in adult patients, imatinib was rapidly absorbed after oral administration in paediatric patients in both phase I and phase II studies.
• In patients with hepatic dysfunction (mild, moderate or severe), peripheral blood counts and liver enzymes should be carefully monitored (see sections 4.2, 4.8 and 5.2).
• Except in newly diagnosed chronic phase CML, there are no controlled trials demonstrating a clinical benefit, such as improvement in disease-related symptoms or increased survival.
• Because most generic drugs are made in India, the cost of the active pharmaceutical ingredient was calculated on the basis of the Indian price of the drug.
• The effect of prior gastrointestinal surgery on drug absorption has not been investigated.
• Therefore, caution should be exercised in patients with cardiac dysfunction.

Your cancer type

Some children and adolescents taking imatinib may have slower than normal growth. You may not be able to become pregnant or get someone pregnant after treatment with this drug. Talk to your doctor before starting treatment if you think you may want to have a baby in the future. It is important not to become pregnant or get someone pregnant while you’re having treatment and for a few months afterwards. Tell your healthcare team if you are finding it difficult to control your weight.

Taking your tablets

Until recently, the closest simile was Copaxone (glatiramer acetate), indicated for multiple sclerosis. Like Gleevec, Copaxone had undergone a dramatic rise in price since its launch; from just over $8,000 in 1996 to approximately $90,000 by 2015. The first generic in 2015 had limited impact on the price of glatiramer acetate.

Generic Imatinib Cuts Costs Without Affecting CML Outcomes

The age of these patients ranged from 8 to 18 years and imatinib was given in both adjuvant and metastatic settings at doses ranging from 300 to 800 mg daily. The majority of paediatric patients treated for GIST lacked data confirming c-kit or PDGFR mutations which may have led to mixed clinical outcomes. In this study 65% of the patients achieved a major cytogenetic response that was complete in 53% (confirmed 43%) of patients (Table 3).

Is Gleevec available as a generic

• Check whether cytopenia is related to leukaemia (marrow aspirate or biopsy).
• Occurrences of severe fluid retention (pleural effusion, oedema, pulmonary oedema, ascites, superficial oedema) have been reported in approximately 2.5% of newly diagnosed CML patients taking imatinib.
• Our estimates assumed full access to all interventions indicated before use of drugs, including surgery, radiotherapy and chemotherapy.
• If cytopenia is unrelated to leukaemia, reduce dose of imatinib to 260 mg/m2.
• This is to help lower your risk of getting COVID-19 while having cancer treatment and until your immune system recovers from treatment.
• The recommended dose of imatinib is 800 mg/day for adult patients with DFSP.
• This includes vitamins, herbal supplements and over the counter remedies.

She says Enhertu would give her extra time with her family – and possibly keep her alive until another new treatment comes along. Claire Rowney, chief executive of charity Breast Cancer Now, says it is « deeply unjust that patients are currently caught in a stand-off between NICE and the pharmaceutical companies”. Jeannie is one of about 1,000 people who can’t access a treatment that could extend their lives because it has not been approved for funding on the NHS in England, Wales and Northern Ireland.

Health Challenges

Another cancer drug for incurable blood cancer myeloma has been rejected too. Shelagh McKinlay, from the charity Myeloma UK, says the bar to get treatments approved “has been raised impossibly high”. He is concerned the severity modifier could make it harder to launch future cancer drugs.

How does the cost of Gleevec 400 mg compare with Gleevec 100 mg?

• « We need to get this information out so that people are negotiating from a position of strength.
• The pharmacokinetics of imatinib have been evaluated over a dosage range of 25 to 1,000 mg.
• In the study in patients with unresectable and/or metastatic GIST, grade 3 and 4 anaemia was reported in 5.4% and 0.7% of patients, respectively, and may have been related to gastrointestinal or intra-tumoural bleeding in at least some of these patients.
• Co-author Dr Nicola Kaciubskyj, also at Norfolk and Norwich University Hospital, explained that there were a range of generic versions available from different suppliers « each obviously ranging in cost savings, but we’ve gone for the cheapest option ».
• To examine disease control and tolerability following the switch, the researchers identified CML patients who were being treated at their hospital in January 2017.
• But if you have health insurance, you’ll need to talk with your insurance provider to learn the actual cost you’ll pay for Gleevec.

Incidence data and assumptions used to calculate eligible population estimates are presented in table 3 for the global population, and in table 4 for the UK population. The recommended dose for bortezomib is 1.3 mg/m2 for a body surface area of 1.8 m2, taken twice a week for two consecutive weeks, followed by a resting week, in a 3-week cycle. This is equivalent to a per-patient yearly API requirement of 159 mg. Even first-to-market biosimilars have seen greater discounts than generic imatinib. Though perhaps disappointing, price discounts for the few biosimilars that are on the market in the U.S. range from 15% to 38%. When first approved, Gleevec ushered in a new era of targeted oncology drugs.

The Curious Case Of Gleevec Pricing

Currently available published data are summarised in section 5.1 but no recommendation on a posology can be made. The estimated price for dasatinib, assuming a dose of 100 mg daily, was £122.95 GBP per year, or £9.43 GBP per month. The lowest available price was from the originator company in Brazil, costing £769.03 per month (figure 2). Chemical structures are shown in figures 3 and 4, with references for these in online supplementary appendix B. API export data sufficient to allow calculation of generic price estimates were only available for dasatinib and gefitinib (table 1). For bortezomib and everolimus, the lowest priced product globally was used for comparisons with UK prices.

Coping with side effects

3 On a patient-year basis, cardiac events including congestive heart failure were more commonly observed in patients with transformed CML than in patients with chronic CML. In thyroidectomy patients receiving levothyroxine, the plasma exposure to levothyroxine may be decreased when imatinib is co-administered (see section 4.4). However, the mechanism of the observed interaction is presently unknown. • the adjuvant treatment of adult patients who are at significant risk of relapse following resection of Kit (CD117)-positive GIST. Patients who have a low or very low risk of recurrence should not receive adjuvant treatment. • adult patients with advanced hypereosinophilic syndrome (HES) and/or chronic eosinophilic leukaemia (CEL) with FIP1L1-PDGFRα rearrangement.

What is the cost of Gleevec with insurance?

Forty-three CML patients were identified, of whom 15 (35%) were female. They had been taking imatinib for a median of 6 years before switching to the generic version. The patient’s medical records were then reviewed up to August 2019 for novel adverse effects, alongside laboratory reports to assess disease status. Charlotte Martin nevertheless added that adverse effects « do impact on quality of life and patients who report changes or problems should have the opportunity to discuss these with their medical team and receive adequate support ». The team highlights that switching to generic imatinib « did not lead to any change in disease control » and the new formulations « were generally well tolerated ». « We were surprised to find several companies consistently raising the prices, » Dr Hill said.

Strengths and limitations of this study

The recommended dose for everolimus is 10 mg daily, equivalent to a per-patient yearly API requirement of 3.7 g. The lowest available generic price globally was £688.96 per month, assuming off-label use, and £851.65 on-label, for Indian products (figure 6). Objectives The aim of this study was to estimate lowest possible treatment costs for four novel cancer drugs, hypothesising that generic manufacturing could significantly reduce treatment costs. This showed that 23% experienced adverse effects on switching imatinib, including recurrence of cramp, transient skin rash, subconjunctival haemorrhage and gastrointestinal upset.

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme (/yellowcard) or search for MHRA Yellow Card in Google play or Apple App store. Patients should be advised that they may experience undesirable effects such as dizziness, blurred vision or somnolence during treatment with imatinib. Therefore, caution should be recommended when driving a car or operating machinery. Because of known increased risks of bleeding in conjunction with the use of imatinib (e.g. haemorrhage), patients who require anticoagulation should receive low-molecular-weight or standard heparin, instead of coumarin derivatives such as warfarin.

Treatment for other conditions

Avoid close contact with people who have recently had live vaccines taken by mouth (oral vaccines) such as the oral typhoid vaccine. Sometimes people who have had the live shingles vaccine can get a shingles type rash. If you are having tests or treatment for anything else, always mention your cancer treatment. Don’t breastfeed during this treatment because the drug may come through into your breast milk.

However, the British Generic Manufacturers Association (BGMA) pointed out that hospital prices for these drugs are negotiated separately through a rigorous tendering system and are much lower than those quoted by the researchers. In the 2-year rat carcinogenicity study administration of imatinib at 15, 30 and 60 mg/kg/day resulted in a statistically significant reduction in the longevity of males at 60 mg/kg/day and females at ≥ 30 mg/kg/day. Histopathological examination of decedents revealed cardiomyopathy (both sexes), chronic progressive nephropathy (females) and preputial gland papilloma as principal causes of death or reasons for sacrifice. Target organs for neoplastic changes were the kidneys, urinary bladder, urethra, preputial and clitoral gland, small intestine, parathyroid glands, adrenal glands and non- glandular stomach. Imatinib was teratogenic in rats when administered during organogenesis at doses ≥ 100 mg/kg, approximately equal to the maximum clinical dose of 800 mg/day, based on body surface area. Teratogenic effects included exencephaly or encephalocele, absent/reduced frontal and absent parietal bones.

• Pretreatment with multiple doses of rifampicin 600 mg followed by a single 400 mg dose of imatinib resulted in decrease in Cmax and AUC(0-∞ ) by at least 54% and 74%, of the respective values without rifampicin treatment.
• That was five and a half years ago – now the cancer has spread to her liver.
• One example is imatinib (Gleevec, Novartis), used for the treatment of chronic myeloid leukemia (CML).
• The adverse effects were mild and the majority were transient, the team reports.
• The researchers say that, when imatinib was approved for clinical use in CML under the Glivec brand, it « transformed » outcomes in terms of progression-free and overall survival.

Importation of Indian generics would represent a UK price decrease of 74% for bortezomib and 71% for everolimus. No generic versions of dasatinib were identified in the countries surveyed. Generic gefitinib was found to be available only in India, for £90 per month. While this price is significantly below than that in other countries (figure 7), it is ninefold the estimated generic price of £10 per month. The current generic price of gefitinib in India is roughly equal, per year, to the median per annum income.

Dr Hill and colleagues documented huge price increases for many generic cancer drugs commonly used in the United Kingdom from September 2011 to September 2016. The team used three databases – Drug Tarriff, British National Formulary, and Prescription Cost Analysis ― noting, « we think this a reliable indicator that the UK pays. » Imatinib and its metabolites are not excreted via the kidney to a significant extent. Patients with mild and moderate impairment of renal function appear to have a higher plasma exposure than patients with normal renal function. The increase is approximately 1.5- to 2-fold, corresponding to a 1.5-fold elevation of plasma AGP, to which imatinib binds strongly. The free drug clearance of imatinib is probably similar between patients with renal impairment and those with normal renal function, since renal excretion represents only a minor elimination pathway for imatinib (see sections 4.2 and 4.4).

There are a number of different tyrosine kinases and blocking them stops the cancer cells growing. « Showing that certain cancers could be treated for very low prices could transform the future of people with cancers in very-low-income regorafenib price philippines countries, where there are usually few or no treatment options, » Barber commented. It could allow for large-scale treatment programs, such as the ones implemented for the treatment of HIV and AIDS in many low-income countries.

Your doctor may give you anti diarrhoea medicine to take home with you after treatment. Tiredness and weakness (fatigue) can happen during and after treatment. Don’t push yourself, rest when you start to feel tired and ask others for help. Or you may have lots of tiny red spots or bruises on your arms or legs (known as petechiae).

Treatment resulted in worsening of normally suppressed malarial infections in these animals. Multiple dose toxicity studies revealed mild to moderate haematological changes in rats, dogs and monkeys, accompanied by bone marrow changes in rats and dogs. Based on the recovery of compound(s) after an oral 14C-labelled dose of imatinib, approximately 81% of the dose was recovered within 7 days in faeces (68% of dose) and urine (13% of dose). Unchanged imatinib accounted for 25% of the dose (5% urine, 20% faeces), the remainder being metabolites.

And because generics have the same active ingredients as brand-name drugs, they don’t need to be studied again. The cost per month of Gleevec if you have insurance depends on your individual plan benefits. For example, you could have a set copay or need to pay a percentage of the cost each time you get the prescription filled. It’s a prescription drug used to treat certain kinds of blood cancers, such as leukemia, in adults and some children. It’s also used to treat a kind of skin cancer and a kind of gastrointestinal cancer in adults. Members of your household who are aged 5 years or over are also able to have the COVID-19 vaccine.