Therapeutic focus – Tough market for new wave of epilepsy drugs
For a therapeutic area that generated an impressive annual growth rate of 16% over the past ten years, the market for epilepsy drugs is set for a dramatic decline following the sudden expiry of key patents for four of the top five biggest-selling blockbuster products within the last nine months. Having peaked at $12.8bn in 2008 sales of epileptic drugs are set to decline 5% annually to $9.32bn by 2014 (see table below).
Nevertheless, a number of new epilepsy drugs are set to reach the market within the next couple of years and assuming they match current expectations could generate significant revenues for the likes of UCB and Johnson & Johnson. For UCB a successful launch of Vimpat in the US and positive phase III data for Rikelta are crucial events this year which will have a strong bearing on the group’s market valuation.
Market heads into reverse
Of the top five epilepsy drugs last year, only Pfizer’s Lyrica is set to continue to dominate the market over the next few years, although it is important to note that a significant portion of forecast sales are also attributed to the drug’s use for neuropathic pain, anxiety and fibromyalgia.
|Anti-epileptic market: top 10 products in 2014||WW annual sales ($m)|
|Rank||Product||Company||Pharmacological Class||Market status||Patent Expiry||2008||2014||CAGR (08 - 14)|
|1||Lyrica||Pfizer||Alpha 2 delta ligand||Marketed||Dec 2018||2,573||4,671||10%|
|2||Vimpat||UCB||CRMP-2 modulator||Marketed||Mar 2017||3||725||150%|
|3||RWJ333369||Johnson & Johnson||Anti-convulsant||Filed||-||-||485||n/a|
|4||Rikelta||UCB||Pyrrolidone||Phase III||Dec 2021||-||438||n/a|
|5||Depakine||Sanofi-Aventis||GABA agonist||Marketed||Jan 2005||483||413||(3%)|
|7||Lamictal||GlaxoSmithKline||Sodium channel antagonist||Marketed||Jan 2009||1,714||322||(24%)|
|8||Neurontin||Pfizer||GABA agonist||Marketed||Jul 2000||387||181||(12%)|
|9||Depakote||Abbott Laboratories||GABA agonist||Marketed||Jul 2008||1,364||145||(31%)|
|Total anti-epileptic market||12,789||9,317||(5%)|
The following table highlights the products that will contribute the most to the overall decline in revenues for epilepsy drugs, as almost 90% of aggregate sales of $8.1bn in 2008 are expected to be lost by 2014.
|Anti-epileptic market: growth brakes (2008 - 2014)||WW annual sales ($m)|
|Rank||Product||Company||Patent expiry||2008||2014||CAGR (08 - 14)||Total change ($m)|
|1||Topamax||Johnson & Johnson||Mar 2009||2,731||127||(40%)||(2,604)|
|4||Depakote||Abbott Laboratories||Jul 2008||1,364||145||(31%)||(1,219)|
New products attempt to offset decline
Behind Lyrica, the importance of successful launches and approvals of three new drugs is clear.
Vimpat, which suffered a significant setback when the FDA rejected its use for diabetic neuropathic pain in July 2008, finally gained approval for epilepsy in October (UCB finally has something to celebrate, October 29, 2008). The setback in the pain setting has already significantly reduced the drug’s commercial prospects. Archive consensus forecasts from EvaluatePharma reveal that since the FDA rejection estimates for sales by 2014 have been trimmed by over a quarter to currently sit at $725m. Vimpat’s imminent launch in the US and initial uptake rate will therefore be of great interest to investors and analysts alike.
The first set of phase III data for another of UCB’s pipeline epilepsy drugs, Rikelta, due in the third quarter, will also provide a binary event for the company’s share price. Currently estimated to be worth as much as $930m, according to EvaluatePharma’s NPV Analyzer, the drug is also the second most valuable product in the Belgian group’s portfolio.
Meanwhile, J&J’s RWJ333369 was filed with the FDA last October and therefore has an estimated PDUFA date in August. Valued at $870m the drug is J&J’s fourth most valuable pipeline candidate and also slated to be one of the biggest product launches this year (Which of 2009's launches will be future blockbusters?,February 17, 2009).
The following table lists some other important late stage clinical candidates which could also help to offset the overall decline in the epilepsy market.
|Anti-epileptic market: R&D pipeline||WW annual sales ($m)|
|Phase||Product||Generic Name||Company||Pharmacological Class||NDA Classification||First Introduction||2010||2012||2014|
|Filed||RWJ333369||carisbamate||Johnson & Johnson||Anti-convulsant||New molecular entity||Dec 2009||139||322||485|
|Lamictal XR||lamotrigine||GlaxoSmithKline||Sodium channel antagonist||NDA||Dec 2009||77||43||11|
|Stedesa||eslicarbazepine||Sepracor||Iminostilbene||New molecular entity||Jun 2010||25||76||119|
|Phase III||Rikelta||brivaracetam||UCB||Pyrrolidone||New molecular entity||Jun 2010||66||242||438|
|Retigabine||retigabine||GlaxoSmithKline + Valeant Pharmaceuticals + Meda||GABA agonist & potassium channel agonist||New molecular entity||Jun 2010||9||54||128|
|DM-5689/DM-1796||gabapentin||Depomed + Solvay||GABA agonist||NDA||Jun 2011||-||35||91|
|Phase II||JZP-8||clonazepam||Jazz Pharmaceuticals||Benzodiazepine||NDA||Jun 2012||-||-||25|
|Ganaxolone||ganaxolone||Marinus Pharmaceuticals||GABA A receptor modulator||New molecular entity||-||-||-||-|
|SRx-502||-||Spherics||CNS agent||New molecular entity||-||-||-||-|
|DP-VPA||-||D-Pharm||Anti-convulsant||New molecular entity||-||-||-||-|
As well as the potentially catalytic events already discussed, the summary below of EvaluatePharma’s Calendar of Events highlights some further important milestones to take place in the epilepsy market this year.
A product largely under the radar and which could yet generate far larger revenues than currently forecast is GlaxoSmithKline’s retigabine. Licensed from Valeant Pharmaceuticals last August for $125m upfront and potentially a further $545m in milestones, Glaxo clearly has high hopes for the drug, although the timing of regulatory filings in both the US and Europe appears to have slipped slightly, from the first quarter to sometime this year.
|EvaluatePharma's Calendar of Events: selected key events for anti-epileptic drugs|
|Event Type||Product||Company||NPV ($m)||NPV as % of Mkt Cap||Event||Event Status||Start Date||End Date|
|US Product Launch||Vimpat||UCB||705||13%||Expect US Launch of Vimpat (lacosamide) for Partial Onset Seizures in Adults with Epilepsy||In-Play (62%)||01 Jan 2009||30 Jun 2009|
|US Product Approval (PDUFA)||Lamictal XR||GlaxoSmithKline||131||0%||FDA Decision Date (PDUFA) on Lamictal XR for Epilepsy||Overdue by 104 days||09 Jan 2009||09 Jan 2009|
|Sabril||Ovation Pharmaceuticals||0||FDA Decision Date (PDUFA) on Sabril for Infantile Spasms (IS) & Refractory Complex Partial Seizures (CPS)||Overdue by 23 days||08 Jan 2009||31 Mar 2009|
|RWJ333369||Johnson & Johnson||870||1%||FDA Decision Date (PDUFA) on RWJ333369 for Epilepsy||Starts in 123 days||24 Aug 2009||24 Aug 2009|
|US Product Filing||Retigabine||GlaxoSmithKline||152||0%||Expect US Filing for Retigabine in Epilepsy||Overdue by 23 days||01 Jan 2009||31 Mar 2009|
|EU Product Filing||Retigabine||GlaxoSmithKline||152||0%||Expect EU Filing for Retigabine in Epilepsy||Overdue by 23 days||01 Jan 2009||31 Mar 2009|
|Phase III Trial Results||Rikelta||UCB||929||17%||Phase III Trial Results for Rikelta as Adjunctive Treatment in Partial-Onset Epilepsy||Starts in 69 days||01 Jul 2009||30 Sep 2009|
|Phase II Trial Results||JZP-8||Jazz Pharmaceuticals||49||257%||Phase II Trial Results for JZP-8 for Epilepsy||In-Play (62%)||01 Jan 2009||30 Jun 2009|