April will begin with decisions from the FDA on the approvability of smaller novel drugs – and there is a fairly large chance that the first two projects to go before the agency, from Evoke and Intelgenx, will get knocked back. Towards the end of the month there could be better news for biopharma, with more substantial products earmarked for verdicts.
Evoke’s hopes of starting April on a high note were effectively dashed in early March when the FDA sent the group a multi-disciplinary review letter regarding its Gimoti NDA filing. The project is an intranasal formulation of metoclopramide that Evoke has developed to treat diabetic gastroparesis in women, in whom the company argues that the active ingredient is most effective.
The regulator raised concerns about chemistry, a lack of adequate clinical data to support sex-based efficacy differences, and clinical pharmacology. The company submitted its response to the letter by March 14 and met with the FDA on March 21, but the lack of any subsequent update makes approval by the April 1 PDUFA date seem highly unlikely.
Also due on the first day of the month is a decision on Intelgenx's Rizaport, which has had a long and tortuous path in its quest for FDA approval. The coming PDUFA date represents the third time the regulator will pass judgment on the migraine project, an oral soluble film formulation of the triptan Maxalt. Intelgenx received a complete response letter to Rizaport's first NDA back in 2013. It took the company until 2017 to resubmit its application, but this was then subject to an incomplete response letter. At this stage marketing partner Redhill Biopharma pulled the plug and Intelgenx pushed on alone in the US, completing a bioequivalence study and resubmitting once again. After years of bungling the process, shareholders will hope the Canadian company has finally got it right.
Next up will be Adma Biologics, which has also had its fair share of issues. The company is hoping for a green light for its lead immune globulin project, RI-001, a speciality polyclonal IVIG designed to prevent infections in patients with primary immune deficiency disease. Adma spent much of 2018 correcting faults at its manufacturing facility and approval of RI-001 would be validation of that work. The company is also awaiting approval to reintroduce Bivigam, an IVIG indicated to treat primary humoral immunodeficiency.
|Notable April first-time approval decisions|
|Project||Company||PDUFA date||Product NPV ($m)|
|Gimoti||Evoke Pharma||April 1||362|
|Rizaport||Intelgenx Technologies||April 1 (3rd review)||-|
|RI-002||Adma Biologics||April 2||183|
|risankizumab/Skyrizi||Abbvie/Boehringer Ingelheim||April 25||6,699|
|HTX-011||Heron Therapeutics||April 30||525|
|Contepo||Nabriva Therapeutics||April 30||22|
|dolutegravir & lamivudine||Glaxosmithkline||April (unconfirmed)||1,130|
The latter part of April will see verdicts on projects with bigger forecasts attached. The most notable is Abbvie’s psoriasis treatment risankizumab, which represents one of the biggest potential launches of 2019. The sellside has pencilled in sales of $2.4bn by 2024 and the omens for approval are good: the anti-IL-23 antibody got a positive opinion from European regulators in February and a green light in Japan in March; in these regions the drug has been branded Skyrizi. The product was developed in collaboration with Boehringer Ingelheim so not all of the economics will flow to Abbvie, but risankizumab represents one of the US pharma giant’s brightest pipeline hopes.
Heron will be hoping that demand for non-opioid-based pain relief will prompt the FDA to green light HTX-011 towards the end of the month. The project is an extended-release formulation of bupivacaine combined with the anti-inflammatory meloxicam. The FDA granted HTX-011 priority review and did not require an advisory committee to review the filing, all of which bodes well for approval in a post-operative pain setting. The sellside is predicting sales of $572m by 2024, according to EvaluatePharma’s consensus, a lofty target that arguably presents Heron with as big a challenge as getting to market in the first place.
Also later in April, Nabriva will learn whether Contepo has passed regulatory muster; the intravenous antibiotic has been filed as a treatment of complicated-urinary tract infections including acute pyelonephritis. Generically known as fosfomycin, the antibiotic belongs to the epoxide class; in Europe, IV fosfomycin has been available generically for many years but has never been licensed in the US. A much bigger opportunity for Nabriva awaits in the form of a second antibiotic called lefamulin, on which an FDA decision is due in August.
A decision is also likely to emerge next month on Glaxosmithkline/Viiv’s second two-drug HIV regimen, dolutegravir & lamivudine. The project represents the companies’ attempt to lower the medicine burden for patients with HIV, and data have shown that certain patients can experience similar virus suppression with only two drugs, rather than the three-drug regimens commonly used. However, there have been concerns about the emergence of resistance. A positive CHMP decision was received late last year.
Finally, Novartis's gene therapy candidate Zolgensma has been included in April’s analysis – the PDUFA date is thought to be in early May, but it is not inconceivable that the FDA will wave the project through earlier. Designed to treat children with spinal muscular atrophy, a degenerative disease that is frequently fatal, its launch is highly anticipated and is expected to drastically change the prospects for sufferers. A green light is widely expected, with the main question being the price at which Novartis will launch. The pharma giant has controversially claimed that a price tag of up to $5m would be justified, and while few expect it to be that high, Zolgensma is highly likely to be the most expensive drug the world has ever seen.
|Supplementary approvals for April|
|Keytruda||Merck & Co||Supplementary approval for first-line NSCLC, PD-L1 ≥1% without EGFR or ALK mutations||April 11|
|Praluent||Sanofi/Regeneron||Supplementary approval to include Odyssey Outcomes survival data||April 29|
Finally two notable supplementary approvals are slated for next month. Merck & Co will hear the FDA’s verdict on Keytruda monotherapy in a broad first-line lung cancer setting, in patients whose tumours express PD-L1 ≥1%. The decision was delayed by three months to allow Merck to submit more data, but the emphatic results generated by Keynote-42 study, on which the filing is based, make approval look highly likely.
And Sanofi and Regeneron will learn whether their marketing teams can start pushing the cardiovascular outcome data generated by Praluent in the Odyssey Outcomes study, an event that would put the anti-PCSK9 antibody on a level footing with Amgen’s Repatha.