Few UK "Promising Innovative Medicine" Holders Seek Joint MHRA/NICE Advice – Rawlins

MHRA chief says too few drug makers granted PIM designation on the basis of early clinical data are making use of joint consultations with the agency and the cost-effectiveness watchdog NICE.

Drug companies granted "promising innovative medicine" designations in the UK on the basis of early clinical data are encouraged to seek joint scientific consultations with the Medicines and Healthcare Products Regulatory Agency (MHRA) and cost effectiveness-oriented National Institute for Health and Care Excellence. But too few are taking advantage of that opportunity, MHRA Chairman Michael Rawlins says, and instead seem to be seeking advice from the European Medicines Agency.

He assumes that in doing so, drug makers are taking a broader European approach.

“It’s with relative rarity that companies at present ask for joint MHRA and NICE scientific advice to help with their drug’s progression. I’d like them to come more often and encourage them to do so,” he said in a recent interview (see related story, (Also see "MHRA’s Rawlins Plans British Version Of FDA’s Reg Science Centers" - Pink Sheet, 24 Aug, 2015.).

The MHRA’s Early Access to Medicines Scheme (EAMS) makes medicines available before marketing authorization for life-threatening or seriously debilitating conditions with a clear unmet need. As one component of the scheme, companies can initially apply for the Promising Innovative Medicine designation on the basis of early clinical data, akin to the US breakthrough designation. At a later stage, the MHRA will consider the evidence and can issue an EAMS scientific opinion to support prescriptions of yet-unlicensed and off-label medicines.

The UK's process complements EMA’s Adaptive Pathways project which encourages greater dialogue between regulators, industry, health professionals and other stakeholders at an earlier stage of drug development. European countries have taken a keen interest in the US various schemes for speeding access to new medicines, such as the breakthrough designation (Also see "U.K. Early Access Scheme Now Open To All Comers, But Smaller Firms May Be Scared" - Pink Sheet, 1 May, 2014.).

While it is too soon to draw any lessons from these initiatives, Rawlins said the early signs were good: "We find that it is possible to deal with a PIM and an EAMS application simultaneously. So far we've had eight PIMs and three EAMS scientific opinions. It seems to be working fairly well."

Merck & Co. Inc.’s PD-1 inhibitor Keytruda (pembrolizumab) when used for melanoma became the first medicine to be made available through the Early Access Medicines Scheme after a positive opinion issued in March by the MHRA after the therapy was shown to slow the progression of metastatic melanoma, a condition where other treatments currently have poor results (Also see "European Notebook: U.K. Early Access Scheme Starts; New HTA Body In Portugal; Doctors Oppose French Health Bill" - Pink Sheet, 23 Mar, 2015.). “Around 400 patients have now received this drug as a consequence” in the UK, Rawlins said.

The first therapy to ever receive PIM designation was US group Northwest Biotherapeutics Inc. for its cell therapy anti-cancer vaccine DCVax-L in September 2014, marking its first step in the early access scheme. Rawlins declined to identify other PIM holders and or EAMS winners for corporate confidentiality reasons.

The two UK regulators have identified an EAMS issue concerning drug availability which they are now discussing.

“The problem with EAMS, in a sense, is that it provides the drug to the patient without charge from the manufacturer. Unfortunately, once the product gets marketing authorization, it is no longer in the EAMS scheme and so there’s a time gap between the marketing authorization and NICE giving its advice to the National Health Service, so that’s the kind of gap we’re thinking about trying to sort out." Rawlins did not outline how the regulators might address that interim gap in product availability.

MHRA And NICE Cooperation On Children's Therapy Guidelines

Cooperation between MHRA and NICE has been especially useful in the area of clinical guidelines, not least because such rules aren’t limited to authorized products, Rawlins also commented.

“Sometimes in clinical guidelines NICE needs to recommend the use of off-label products particularly where we’re talking about children, so NICE often interacts with the MHRA to find out if there’s been any experience, or if the MHRA is aware of particular problems of using products in children that have only been licensed for use in adults. I think there’s only one or two products licensed for use for malignant disease in children. The treatment of acute leukemia, for example, which is very effective and curative, is almost entirely done with off-label usage. That’s another story, but we have close interactions with NICE over this, and it’s important that we do when it comes to safety,” Rawlins said.

[Editor's note: This story was also published in Scrip Regulatory Affairs. "The Pink Sheet" brings selected complementary coverage from our sister publications to subscribers.]