Diurnal Adrenal Franchise Takes Shape With Alkindi Launch
Executive Summary
With the launch in Germany of Alkindi, Diurnal has kickstarted its plan of offering therapies that treat patients with cortisol deficiency diseases from birth right the way through to old age and the market is potentially a very lucrative one.
Very few UK biotechs have taken a product from concept to commercialization under their own steam but Diurnal has managed it, having launched Alkindi (immediate-release hydrocortisone) earlier this month in Germany as replacement therapy for adrenal insufficiency (AI) in infants.
It has been "a long hard slog" for the company which was founded as a spin-out from the University of Sheffield back in 2004, CEO Martin Whitaker told Scrip in an interview. However, Diurnal has moved quickly since getting European marketing authorization for Alkindi in February 2018, with the German launch being announced May 15. (Also see "Seven New Drugs Approved In EU In First Two Months of 2018" - Pink Sheet, 28 Feb, 2018.)
Whitaker said that while the EU approval covers people up to the age of 18, the initial marketing focus will be on patients aged 0-6 years where the unmet need is highest. Diurnal estimates that there are approximately 4,000 patients in Europe under six years old requiring replacement therapy for AI due to congenital adrenal hyperplasia (CAH), primary adrenal failure or hypopituitarism.
In Germany there are about 500 potential patients and was chosen for the first launch, the CEO said, as it is "usually the quickest country out of the blocks for getting a price." That price is about $6,000-$7,000 per annum, which is in line with the only other approved modified hydrocortisone product, Shire's Plenadren, which is approved for adults. Whitaker added that the UK "is not too far behind," with a launch planned in the next month or so, followed by the Netherlands.
Diurnal got approval by using the European Medicines Agency's pediatric-use marketing authorization (PUMA) pathway, an experience that Whitaker said was extremely positive. The company made its initial PUMA application back in 2011 and presented a pediatric investigation plan to the EMA and it took six to nine months to agree on the clinical trial plan, ending with a successful readout in the second half of 2016.
He noted that hydrocortisone has been marketed for 60 years, but no other company had applied for a licence for an immediate-release formulation for use in children. Adrenal insufficiency in children is currently treated by compounding hydrocortisone or crushing/splitting tablets only approved for adults.
Acknowledging that not a lot of companies have taken the PUMA route, Whitaker stressed that there has been a strong drive spearheaded by the EMA to start producing clinical data specifically for children and from a commercial standpoint for small and medium-sized enterprises (SMEs) like Diurnal, the incentives are considerable - 10 years of market and data exclusivity. When it comes to pediatric drugs, the EMA "has grasped the nettle," he added.
As for Diurnal's commercialization plans for Alkindi, it has teamed up with global contract sales organisation Ashfield Healthcare, part of UDG Healthcare, to build infrastructure in the major European territories. Whitaker told Scrip that it was not necessary to have a sales force on the ground from day one, given the wide variety of reimbursement challenges across the continent, so the Ashfield agreement gives the company greater flexibility – in Germany it has two medical liaison staff in place and two reps and he added that the company has an experienced in-house commercial team, working out what data each country needs to reimburse the product.
The company, which raised £11m in a placing in March, has also signed marketing and distribution deals in Israel, as well as in Australia and New Zealand, countries where submissions of Alkindi will be adapted from the data package used by the EMA. Approvals are expected next year and in 2020.
As for the US, Whitaker noted that the filing of Alkindi is expected in late 2018, with potential for FDA approval in 2020. Also across the pond, a Phase III trial is due to start before the end of the year of Chronocort, Diurnal's second product and a cortisol replacement product for adults patients with CAH. Patient recruitment in a European Phase III trial for CAH in adults has now been completed, with top-line results expected before the end of the year.
Analysts are impressed with Diurnal's business model and the team at Hardman & Co issued an investor note recently noting that the firm "has been considered to have unusually low risk because its products are formulation variants of well-established drugs. This has been validated with the European approval of Alkindi [and] the main risk now is that of commercial execution."
They add that with Alkindi and Chronocort, "the aim is to create a long-life adrenal franchise," where patients start with the former and will then move on to the latter for the rest of their lives. Hardman noted that the cortisol replacement market is for conditions that need life-long treatments and has a potential value of $3.5bn.
The rarity of an SME taking a product to market on its own has not escaped the attention of the bigger players in the pharmaceutical world. Whitaker said things are going to plan with one product launched, a second on the way and revenues being generated in not-too-distant future. "The phone has been ringing steadily," he told Scrip, adding that smaller innovative companies that get to market will inevitably attract interest.