NEW YORK (GenomeWeb) – Out of 42 cancer drug indications that the NHS has said it will reconsider whether or not to continue providing to patients in England, approximately a dozen therapy indications are for molecularly defined patient populations.
Many of these personalized cancer therapies carry a high price tag. Under the evaluation process, in order to keep the drugs in the fund, drugmakers will have to meet a cost and clinical efficacy threshold. NHS will also offer drugmakers the chance to provide their treatments at a discount to meet the cost threshold.
Last week, the NHS England announced that it will reevaluate the drugs available through its Cancer Drugs Fund (CDF) – a program launched in 2011 to make cancer drugs available to patients that normally wouldn't be available through the health system. Many of the drugs on the list did not pass muster under the National Institute for Health and Care Excellence's (NICE) cost-effectiveness analysis or were indicated for rare cancers that fall outside of NICE's scope.
According to the NHS, it spends £1.3 billion ($2.04 billion) on cancer drugs each year through its regular fund. The CDF was launched to provide additional resources for cancer drugs on top of the existing budget. In the time that the CDF has been available, the fund has provided treatments to more than 55,000 patients, or around 2,000 patients every month.
Earlier this year, the NHS decided to bump up CDF's budget by 40 percent to £280 million. But now, the health service wants to ensure that these additional funds are judiciously spent on drugs that yield the best results for patients and that the fund stays around in future years, the NHS has said.
NHS consulted stakeholders on its proposed CDF assessment process before deciding to move ahead with its plan. CDF Chair Peter Clark, who is also an oncologist, said in a statement that the reevaluation is necessary to "make sure that the [fund] delivers drugs which offer good clinical benefit at reasonable prices so the CDF can treat the largest number of patients." He added that the reevaluation is "absolutely the right thing to do for patients."
Among the drugs slated for reevaluation are a number of therapies that are indicated for a molecularly defined subset of patients, such as Genentech's new HER2-targeted breast cancer drugs – Perjeta (pertuzumab) in the first-line metastatic setting and Kadcyla (trastuzumab emtansine) in second-line or later stages of metastatic disease – and Pfizer's Xalkori (crizotinib) for second-line ALK-positive metastatic non-small cell lung cancer. Also on the list are a number of the newer leukemia drugs, particularly those indicated for Philadelphia chromosome-positive variety.
The NHS is also evaluating whether to provide through the CDF a handful of new personalized cancer drug indications, such as Gilead's Zydelig (idelalisib) in first-line chronic lymphocytic leukemia for high-risk patients who have a 17 p deletion or a TP53 mutation; Amgen's Vectibix (panitumumab) in second- and third-line colorectal cancer with RAS wild-type tumors; and Plexxikon/Genentech's Zelboraf (vemurafenib) as a last option for hairy cell leukemia patients with BRAF V600 mutations.
An NHS spokesperson explained to GenomeWeb in an email that the CDF panel, which includes oncologists, pharmacists, and patient representatives, will establish a single threshold for all the drugs slated for reevaluation. Whether a drug meets that threshold will be determined based on a combined score that factors in the cost-effectiveness of the treatment, as well as the clinical effectiveness.
Generally, NICE tends to recommend that NHS fund drugs that don't exceed an incremental cost-effectiveness ratio of £30,000 per quality-adjusted life year. However, according to the NHS spokesperson, the cost/clinical-effectiveness threshold for the drugs reevaluated under the CDF will remain confidential between the drugmakers and the CDF panel.
"All pharmaceutical companies which have a drug on the reevaluation list will be invited to collate any new evidence which they feel will support the assessment of their drug with a view to remaining on the CDF list, and will be invited to present their case at the meeting of the CDF panel in December," the NHS spokesperson said. "There will be an opportunity for companies to offer a reduced price for drugs that are reevaluated."
The clinical-effectiveness factors the panel will consider will include a drug's impact on patients' progression-free survival, overall survival, quality of life, and toxicity, as well as whether it addresses an unmet need. The panel will consider cost by assessing whether budget impact models support the median per-patient cost for a drug submitted by the sponsor. These two scores will be combined to yield a final score for each drug.
"Each medicine and its indication will then be ranked and a 'cut-off point' will be applied, below which the indication will be at risk of being removed from the CDF," a spokesperson from Genentech's parent firm Roche told GenomeWeb over email. "Each company will then have the opportunity to offer a commercial scheme. If the proposition raises the combined score past the cut-off point, the indication will remain available through the CDF."
Many of the drugs on CDF's reevaluation list are personalized cancer therapies sold by Genentech that, in principle, are thought to add value to the care of patients. Still, while these drugs have shown to benefit molecularly-defined patient populations, these treatments are pricey. As such, drugs like Kadcyla and Perjeta were not found cost-effective by NICE and not funded by NHS through its regular process.
In the case of Perjeta, for example, NICE said that at a price of £2,395 per 420 mg vial, the clinical evidence on the drug did not convincingly show that it could extend patients' lives to warrant a positive recommendation. NICE similarly rejected the ALK inhibitor Xalkori due to its high price – the NICE committee estimated an incremental cost-effectiveness ratio of £96,000 per QALY gained for the drug – and lack of evidence showing the treatment improves overall survival.
Although Perjeta and Xalkori have been available to patients through the CDF under the reevaluation process, the government will not take into account "wider considerations of value or cost savings to the NHS," the Roche spokesperson said. "The methodology being employed will only take into account the median cost for the drug, which will be calculated using the cost of a vial of medicine and the duration of treatment."
The CDF panel will meet in December to evaluate the evidence on a drug and decide whether it remains on the list or is removed. The panel's decisions will be published at the beginning of next year.
If the panel finds that a drug on the reevaluation list does not meet its threshold and decides as a result to stop funding it, patients already on the treatment can continue to receive it. If a doctor believes that a patient could benefit from a drug that's not on the list, the patient can apply to CDF to make an exception. Also, if a drug on the CDF is the only option for patients with a certain kind of cancer, they will continue to have access to it through the fund.
"As the CDF has a limited time left, and a new long-term system for assessing the value of cancer medicines is desperately needed in England, Roche hopes that there will soon be opportunities to learn from and improve upon the CDF assessment process," the Roche spokesperson said. "We are keen to work with the government, NHS England, and NICE to arrive at sustainable long-term approaches to evaluating the benefit of cancer medicines, including targeted medicines with smaller patient populations."