10 Potential Drug Approvals To Look Out For In 2016
This article was originally published in Scrip
2015 was a busy year for both the US FDA and the EMA, with both agencies reporting a substantial uptick in the numbers of novel products they approved, but what product approval decisions are due in 2016?
Here Scrip looks at 10 of the more interesting approval decisions to look out for in 2016, in rough order of when they are expected. It is perhaps telling that each of the 10 applications is due to be decided upon first in the US, and so the list is in approximate order of their Prescription Drug User Fee Act (PDUFA) action dates (where known). However, it should be noted that last year many oncology drugs were approved well ahead of their PDUFA dates, a trend that could well continue.
You can view the list in two ways: in a timeline format below, or as plain text further down.
BioMarin's Kyndrisa (drisapersen) and Sarepta's eteplirsen for muscular dystrophy
US approval decision: January 2016
EU approval decision due: drisapersen Q3 2016
US approval decision due: eteplirsen February 2016
EU approval decision due: eteplirsen not yet filed
Regulatory decisions are finally expected for two investigational treatments for the orphan disease Duchenne muscular dystrophy (DMD) this year. The FDA has just given its negative verdict on BioMarin's drisapersen which came as no surprise following an FDA panel in November that was highly skeptical of the company's data for the product, both for efficacy and safety. In its Complete Response Letter, the agency said it wants another Phase III trial, kicking drisapersen into the long grass. Its future will likely depend on how the EU's CHMP responds to the product (a decision is due in the first half), and on how Sarepta's rival product eteplirsen fares at its own panel meeting on Jan. 22. Eteplirsen has a PDUFA action date of Feb. 26. Both drugs are seeking the approval to treat patients with DMD amenable to exon 51 skipping. Duchenne is the most common fatal genetic disorder diagnosed in childhood – affecting about 1 in every 3,500 live male births, with about 20,000 new cases diagnosed globally each year. Also eteplirsen and drisapersen both won the FDA's rare pediatric disease designation, which means they are eligible for a priority review voucher (PRV) on approval. Sarepta has yet to file eteplirsen in the EU.
Eli Lilly's ixekizumab for psoriasis
US approval decision due: first quarter 2016
EU approval decision due: second half 2016
If the regulators are willing, Lilly's offering in the new anti-IL17 class is set to challenge Novartis's frontrunner Cosentyx (secukinumab) which reached the market last year for moderate to severe plaque psoriasis (the first of a number of potential anti-inflammatory conditions). Together these products are pushing back the treatment frontiers in this disease, raising the bar for their followers. So much so that AstraZeneca transferred its IL17 product brodalumab to Valeant after its partner Amgen pulled out of their co-development deal after suicidal ideation adverse events came to light during clinical trials. Ixekizumab and secukinumab may be snapping at the heels of the current standard of care Johnson & Johnson's Stelara (ustekinumab), which superseded the older anti-TNFs in moderate to severe psoriasis, but other products are on the way: a number of anti-IL23 agents are in late-stage development by Boehringer Ingelheim, Merck & Co and J&J.
Datamonitor 7MM sales forecast 2023 $297m
Clovis Oncology's rociletinib for NSCLC
US approval decision due: March 2016
EU approval decision due: mid-2016
Clovis shocked investors in November when it released response rate data for rociletinib in non-small-cell lung cancer (NSCLC) that were lower than the firm had previously reported. What's more, the data submitted to the FDA could delay any approval, with the PDUFA action date likely being pushed past the currently scheduled Mar. 30. The rolling filing was for the treatment of patients with mutant epidermal growth factor receptor (EGFR) non-small cell lung cancer who have been previously treated with an EGFR-targeted therapy and have the EGFR T790M mutation as detected by an FDA approved test. Analysts had hoped that the product would sail to market, like AstraZeneca's similar product Tagrisso (osimertinib) did in the same indication, in November, well ahead of its PDUFA action date of Feb. 6, 2016. Now they expect a decision in the middle of the year at the earliest; with a worst-case scenario being that the FDA requires data from the TIGER-3 trial which would push approval back until 2017. Clovis can at least take some comfort in the progress of its other offering rucaparib. Its NDA submission timeline has been brought forward to Q2 2016, and the company is eyeing a potential US launch for advanced ovarian cancer by the end of 2016.
Teva's Cinqair (reslizumab) for asthma
US approval decision due: March 2016
EU approval decision due: second half 2016
This is Teva's answer to GlaxoSmithKline's newly approval Nucala (mepolizumab), which last year became the first product licensed in this new class of anti-IL-5 products for severe asthma with an eosinophilic phenotype – a very difficult to treat population, which makes up about 3% of the 25 million people with asthma in the US. Teva is seeking to market iv reslizumab to reduce exacerbation, relieve symptoms and improve lung function in adults and adolescents 12 years or above with asthma with elevated blood eosinophils who are inadequately controlled on inhaled corticosteroids. And it looks set for approval in at least some patients: the FDA's Pulmonary-Allergy Drugs Advisory Committee on Dec. 9 lent its support to reslizumab as a treatment for adults with severe asthma, but said there were not enough data about whether the drug is safe and effective in adolescents 12-17 years. However, a similar verdict from the same committee for Nucala was ignored by the FDA which later approved Nucala for patients 12 years or older – might it do the same for Cinqair?
Datamonitor 7MM sales forecast 2024: $815m
AbbVie/Roche's venetoclax for chronic lymphocytic leukemia
US approval decision due: April 2016
EU approval decision due: November 2016 – May 2017
AbbVie and Roche's B-cell lymphoma-2 (BCL-2) inhibitor has been filed for US and EU approval on the basis of Phase II data in which a clinically meaningful proportion of relapsed, refractory and previously untreated CLL patients with a 17p deletion achieved an objective response. Another Breakthrough Therapy designate, Venetoclax selectively inhibits the BCL-2 protein, which prevents apoptosis in some cells, including lymphocytes. It is thought the drug's mechanism "may help restore the natural process that allows these leukemic cells to self-destruct," representing a new way to treat CLL patients with a 17p deletion – a group with few effective treatment options. Up to 10% of newly diagnosed CLL patients each year have a 17p deletion, and about 30% to 50% of relapsed and refractory CLL patients have a 17p deletion.
The product will have to muscle into an increasingly crowded field, however. AbbVie's own Bruton's tyrosine kinase inhibitor Imbruvica (ibrutinib) and Gilead's PI3K delta inhibitor Zydelig (idelalisib) are other options available and analysts say the key question, if approved, is where this product will fit into the therapeutic sequence. Then again, there is also the option to combine it with Imbruvica, further bolstering AbbVie's oncology portfolio.
AbbVie's NDA was granted a priority review, meaning that its approval should come in the last week of April. An EU decision is expected between November 2016 and May 2017.
Acadia's Nuplazid (pimavanserin) for Parkinson's disease
US approval decision due: end of April 2016
EU approval decision due: not yet filed
Nuplazid's development has been characterized by delay after delay, but September finally saw Acadia file an NDA for Parkinson's disease psychosis after new CEO Steve Davis took the helm. If approved, Nuplazid (pimavanserin) would represent a new and distinctly different pharmacological approach to treating psychosis and would be the first drug approved in the US for psychosis associated with Parkinson's disease. In a Phase III clinical trial, Parkinson's patients treated with the selective serotonin inverse agonist (SSIA) that preferentially targets 5-HT2A receptors had twice the improvement in psychosis as individuals who received a placebo. Patients benefited from the drug without side effects associated with antipsychotic medicines that often are prescribed off-label to people with Parkinson's disease psychosis. Nuplazid has Breakthrough Therapy designation and priority review status, with a PDUFA data of May 1 (which falls on a Sunday, so the decision is expected the Friday before). An MAA filing is planned between March and June this year. About 40% of Parkinson's patients experience psychosis characterized by hallucinations and delusions.
BMT worldwide sales forecast $487.5m in 2025
Portola's andexanet alfa for coagulation reversal
US approval decision due: August 2016
EU approval decision due: not yet filed
Filed in the US in November, this is the second of two anticoagulant antidotes approaching the market which, it is hoped, will boost sales of the new generation of blood thinners (the other one being Boehringer Ingelheim's idarucizumab, which was approved late last year in the US and EU). The newer oral anticoagulants products were a welcome alternative to warfarin in reducing the risk of blood clots that can cause heart attacks and strokes in a variety of clinical settings, but doctors sometimes need urgently to reverse their effects in cases of hemorrhage or when emergency surgery is indicated. The lack of antidotes to these products (as compared with warfarin, for which vitamin K is used), has left prescribers cautious and uptake has been slower than hoped. While BI's idarucizumab was developed for use with its direct thrombin inhibitor dabigatran, Portola's product is aimed at use against the range of Factor Xa inhibitor products, including apixaban (BMS/Pfizer's Eliquis), and rivaroxaban (Bayer/J&J's Xarelto). Andexanet alfa is due to be filed in the EU this quarter.
Andexanet alfa was designated a Breakthrough Therapy by the FDA and if approved will be the first universal antidote for Factor Xa inhibitor anticoagulants. The FDA assigned a PDUFA date of Aug. 17, 2016 under an Accelerated Approval pathway, and all being well launch is expected later this year.
Amgen's etelcalcetide for secondary hyperparathyroidism
US approval decision due: August 2016
EU approval decision due: August 2016 – February 2017
This product is being positioned as the follow-on to Amgen's blockbuster Sensipar (cinacalcet) which is due to go off patent in 2018. Secondary hyperparathyrdoidism (SHPT) affects about two million people who are currently on dialysis and is caused by an increase in parathyroid hormone as kidney function declines. Etelcalcetide's main benefit appears to be its dosing: it is given iv three times a week at the end of each dialysis session, compared with once daily oral dosing with Sensipar which can involve many tablets per day to normalize serum calcium levels. Also known as AMG 416, etelcalcetide is a calcimimetic agent that binds to the calcium channels and decreases the production of the hormone. It was filed for US approval last autumn and with a standard review has a PDUFA date of Aug. 24. Amgen announced its MAA filing for the treatment of SHPT in adult patients with chronic kidney disease on hemodialysis therapy using the centralized procedure in early September.
CTI BioPharma and Baxalta's pacritinib for myelofibrosis
US approval decision due: September – November 2016
EU approval decision due: not yet filed
Pacritinib is an investigational oral kinase inhibitor with specificity for JAK2, FLT3, IRAK1 and CSF1R, currently under US review as a treatment for patients with intermediate and high-risk myelofibrosis with low platelet counts of less than 50,000 per microliter (<50,000/µL). The disease is a rare and serious chronic blood cancer that can affect patients of all ages with a median age of 65 years, with an estimated prevalence in the US of about 18,000 patients. The only product specifically approved for myelofibrosis is Novartis's JAK 1 and 2 inhibitor Jakafi (ruxolitinib), which was approved in 2011 for the treatment of patients with intermediate or high-risk myelofibrosis, including primary myelofibrosis or post-polycythemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis. The pacritinib NDA was based mainly on CTI BioPharma's randomized, open-label, multicenter PERSIST-1 Phase III trial, which compared the product with best supportive care (not including a JAK inhibitor) and showed consistent rates of spleen volume reduction and control of disease-related symptoms across all intermediate or high-risk myelofibrosis subgroups. The rolling NDA was initiated in November 2015 and completed earlier this month and so BMT expects a decision between Sept. 23 and Nov. 5, 2016, assuming an accelerated review time. An EU filing is due early this year.
Sanofi/Regeneron's sarilumab for rheumatoid arthritis
US approval decision due: October 2016
EU approval decision due: not yet filed
The highly competitive anti-inflammatory segment saw another novel offering filed last year, a product of the R&D alliance between the French giant Sanofi and Regeneron Pharmaceuticals. Like Roche's marketed blockbuster arthritis treatment Actemra (tocilizumab, currently the only IL inhibitor licensed for RA), sarilumab inhibits the interleukin-6 receptor, but it is a fully human monoclonal antibody, rather than being humanized. It seems its fate on the market will rest on how well it can differentiate itself not only from Actemra, but also from Johnson & Johnson/GlaxoSmithKline's fully human anti-IL-6 antibody sirukumab in Phase III for rheumatoid arthritis (positive top-line results in moderate to severe disease were reported in December). Moreover, the arrival on the market of biosimilar anti-TNFs is expected to have a more profound impact of the RA market. Their anticipated lower price compared with the branded agents will drive uptake, with payers heavily influencing prescribing decisions. The BLA filing was accepted for review for the treatment of patients with active, moderate to severe rheumatoid arthritis; the PDUFA date is set for Oct. 30, 2016 (as this date falls on a Sunday, a decision is expected on Friday, Oct. 28). An EU submission, however, is not expected until late 2016.
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