Market access roundup: UK HTA shakeups as Brexit fears deepen

With a Brexit deal still out of sight, there have been intensified warnings in the UK about potential disruptions to medicine supplies that could follow a no-deal scenario.

One government minister has said that a no-deal Brexit could disrupt medicines supplies to the UK for at least six months because of delays as they are shipped across the channel, instead of the previously estimated six weeks.

The website Hospital Pharmacy Europe reported that manufacturers may have to rethink logistics arrangements to avoid the delays when medicines are shipped via crossings at Dover and Folkestone.

It cited a letter from MP Stephen Hammond, sent this month, written in response to questions from the House of Lords EU Home Affairs Sub-Committee about access to medical supplies if no deal is reached by 29th March.

Delays could affect “critical” prescription-only and pharmacy drugs, and UK manufacturers, Hammond warned in the letter.

Flying medicines in by air freight is one option under consideration to avoid delays and maintain the supply, but Hammond gave no further information about which medicines would be prioritised.

In the letter he said the Department of Health and Social Care is exploring this option, but said arrangements with air freight companies are commercially confidential.

Meanwhile, Ipsen CEO David Meek warned that US, European, Japanese and Chinese patients could get novel medicines ahead of patients in the UK after Brexit.

Meek told pharmaphorum that the country is likely to slip down the company’s list of priorities when it comes to filing new drugs for approval with regulators.

He said: “(Today) we prioritise the FDA and the EMA and then we do the next markets, for example the PMDA in Japan. China’s FDA has made some announcements about global trials and global drug development, and being the second largest market today China’s FDA would certainly move up in the queue.

“Then you have the other markets such as Swissmedic, Health Canada, Australia – the UK would fall into that basket.”

The warnings emerged as the UK government rushes emergency legislation through Parliament to ensure medicines regulation continues in the increasingly likely event of a no-deal Brexit.

The UK’s Medicines and Healthcare Regulatory Agency (MHRA) looks set to take on the responsibilities of the European Medicines Agency (EMA) after that date, and is working through a set of proposals on how to manage functions such as assessing safety and efficacy of drugs.

The plans include targeting certain products to review after a positive opinion from Europe’s Committee for Medicinal Products for Human Use (CHMP), and three new assessment procedures for products containing new active substances and biosimilars.

Meanwhile, NICE is turning its eye to collaborations outside of Europe. The UK’s cost-effectiveness regulator announced this month that it had joined with the Canadian Agency for Drugs and Technologies in Health (CADTH), in a joint scheme that aims to help drug developers gather cost-effectiveness data during the clinical trial process.

The two health technology assessment (HTA) agencies have many methodologies in common and value the opportunity for early engagement with companies targeting the English and Canadian markets.

The paid-for advice will help those companies prepare for future health technology assessments by answering their questions and providing key insight on their clinical and health economic development plans.

This parallel advice service features a joint summary, highlighting areas of synergy from the two agencies, and two separate advice reports from NICE and CADTH.

Priority Reviews boost AbbVie and Roche

It’s not exactly uncommon for the Food and Drug Administration (FDA) to grant a drug Priority Review status, but such news still acts as a positive sign of a drug’s potential.

So the announcement this month that AbbVie’s rheumatoid arthritis (RA) JAK inhibitor upadacitinib has been granted the status by the US regulator suggests that the company is one step closer to stepping out from the shadow of Humira.

Trial data has suggested that upadacitinib, a JAK1-selective inhibitor, is more effective at treating RA than Humira. Some analysts predict sales could eventually reach $3 billion a year or more.

Humira is the biggest selling drug in the world, but may not hold that position for much longer in the face of growing biosimilar competition – thus AbbVie has been keen to diversify its portfolio.

Nevertheless, upadacitinib will face two main JAK inhibitor competitors – Eli Lilly’s Olumiant and Pfizer’s Xeljanz. Despite excitement surrounding the class, though, these treatments all face a complex, competitive market – especially with a number of low-cost biosimilars of injectable biologics on their way.

But the advantages of convenient oral administration with JAK inhibitors may override cost considerations that would otherwise favour biosimilar uptake.

Still, AbbVie will be keeping a close eye on news that Pfizer is moving patients to a lower dose of Xeljanz in a clinical study, after a safety signal emerged in the trial of patients at high risk of cardiovascular events.

AbbVie said it anticipates a regulatory decision on upadacitinib from the FDA in Q3 2019. The drug is also under review by the European Medicines Agency for the treatment of adult patients with moderate to severe rheumatoid arthritis.

Roche also benefited from two Priority Reviews this month – for personalised lung cancer medicine entrectinib and lymphoma treatment polatuzumab vedotin.

Entrectinib is a selective tyrosine kinase inhibitor being developed for non-small cell lung cancer (NSCLC) patients whose tumours carry NTRK fusions or ROS1 fusions.

The drug has also been granted Breakthrough Therapy Designation by the FDA, priority medicines (PRIME) designation by the EMA and Sakigake designation by the Japanese health authorities.

Roche added entrectinib to its pipeline when it acquired oncology biotech Ignyta for $1.7 billion in 2017, boosting its position in the extremely competitive lung cancer field.

Meanwhile, the Swiss firm’s polatuzumab vedotin has been granted priority review for the treatment of people with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL)  in combination with bendamustine plus Rituxan (rituximab).

Medicare coverage for CAR-T on the horizon

Medicare could soon cover CAR-T therapies under new proposals from the US’ Centers for Medicare & Medicaid Services (CMS), which aim to also gather real-world evidence to eventually inform expanded coverage.

Currently, local Medicare Administrative Contractors have discretion over whether to pay for CAR-T treatments.

The proposed National Coverage Determination would require Medicare to cover the therapy nationwide when it is offered in a CMS-approved registry or clinical study, in which patients are monitored for at least two years post-treatment.

Although this means that access would initially still be limited, evidence from the registries and studies would help CMS identify the types of patients that benefit from CAR-T therapy, informing future decisions about the types of cases in which Medicare would cover the treatment with no registry or trial requirement.