The German Biosimilars Breakthrough That Never Was

It looked as if Germany had, via a new law in place since Oct. 1, allowed automatic substitution of biologicals with biosimilars. Such a move would have shaved 25% off the country's pharmaceuticals budget and set an important precedent in this nascent field, whose commercial success has so far been severely dampened by the restrictions on such substitution. There was plenty of excitement over the summer.

But it was misplaced. The legislation is in fact far more restrictive. The law permits a pharmacist to substitute a product for “an identical product”, even if the brand name is different. This could happen if a doctor prescribes only by active ingredient or does not rule out the substitution of a branded product for a product that contains the same active ingredient.

It sounds rather like generic substitution, but of course this cannot be the case, because biosimilars are not copies of the originator, they are simply “similar” – and this is the crux of the issue. The leading group of health insurers and the German pharmacists association have therefore agreed that in the case of biological products only those biologics that contain the same raw material and undergo the same manufacturing process are “bio-identical” and qualify for substitution.

This basically means that pharmacists may substitute biosimilars for biosimilars – and not for originators. Just to make sure that no-one confuses the issue any further, the agreement lays down specific substitution groups. For example, the first group consists of Medice’s Abseamed, Sandoz’s Binocrit, Hexal's Epoetin Alfa, because the epoetin alfa active ingredient in all of them is supplied by the same production firm.

So original biotech products remain a protected species for now, much to the frustration of the generics industry association, ProGenerika, which points out that substituting biosimilars for one another does not save any money. Instead, it discourages companies from manufacturing these expensive products because they face immediate competition.

But, leaving the summer madness behind us, there may yet be some hope on the horizon for a quiet revolution for biosimilars in Germany. A guideline on the administration of erythropoietin stimulating agents for the treatment of symptomatic renal anemia came into force at the end of September. It endorses the findings of the European Medicines Agency and states that ‘all available ESAs should be considered comparable in terms of therapeutic application’. The quality, safety and efficacy of approved biosimilars has been ‘adequately proven in the approved indications’, it adds. The first shot has been fired.

-- Faraz Kermani

image by flickrer caribb used under creative commons

The End of Free Drug Pricing in Germany?

According to local press, Germany's health minister Philipp Roesler is about to open fire against the branded drug industry with a proposal to break the sector's so-called 'price monopoly' and force them to negotiate lower prices directly with insurers.

Until now, Germany has been one of Europe's last bastions of "free" upfront drug pricing. Sure, the hurdles come afterwards, but both there and in the UK drug firms have--until now--been allowed to set more or less the price they like for new drugs.

"Focus" magazine reported on Saturday that Roesler would impose upon the branded sector fixed price ceilings for their products, should they not come to an agreement with the insurers. Either way, he's gunning for annual health care cost savings of €2 billion.

Direct price negotiations between insurers and drug firms have been legal since 2007. Unsurprisingly though, few if any branded companies have engaged in price-centric dealmaking (or indeed any dealmaking). Most prefer instead to focus on providing other benefits such as supporting compliance.

Meanwhile, as we reported in-depth last year in IN VIVO, the country's largest insurers have already squeezed out over €500 million in savings from the generics sector through inviting best-deal bids for two-year 'preferred supplier' contracts. That trend looks set to continue as firms compete for the next round of contracts.


This is also very likely what's prompting Roesler to try twist the branded sector's arm into likewise negotiating more competitive deals with insurers. We can't imagine that Christopher Hermann, chief negotiator and deputy CEO at the country's largest insurer, will have much to complain about. Frustrated up until now by the branded sector's reluctance to negotiate on price, he nevertheless appeared to see this coming when, back in early 2009, he told us: "I expect contracts around on-patent drugs to become more numerous, as in the next months and years there will be more contracts between health insurance funds and independent doctors' associations in Germany."

His point: insurance funds' negotiating clout is increasing as they wield more and more influence over precisely what drugs doctors prescribe (even though they're not allowed to dictate what drugs are prescribed, as they are in the case of generics).


Lesser of Two Evils?


If Roesler's plan is put into action, drug firms are unlikely to be able to afford to resist, given the alternative: imposed price ceilings that could impact prices not only in Germany, Europe's largest market, but also more broadly across Europe given that Germany service as a reference price market in several other (fixed-price) countries. Negotiating with sick funds may offer industry a little squeeze-room, for instance to provide or fund supplementary services. Such agreements also exempt them from an assessment by IQWiG, Germany's cost-benefit watchdog.

Indeed, another element of Roesler's plan--due to be presented this Wednesday--will allegedly require drug firms to submit, in parallel with a new drug application, a benefit-assessment study of their product, showing which patients the product will serve and which comparator drugs, if any, are already available.

None of this is particularly surprising in today's era of government spending cuts and (continued) targeting of drug manufacturers to make their quick-wins. But whilst it tastes bitter, it may also be an (the last?) opportunity for firms to avoid government-imposed price cuts.

Indeed, Novo Nordisk's CEO Germany, Willi Schnorpfeil , told us in mid-2009 that he would like to see a de-regulated market in Germany with price negotiations between drug firms and payors permitted from day one, as soon as a drug is authorized. Such a system—replacing the current set-up of free up-front pricing with complex rebate solutions and, potentially, centrally determined cost-benefit assessments slapped on thereafter--would allow faster market access to be a negotiating factor, too, he argued.

image by flickrer finlaystewart used under a creative commons license

"We're Not Like NICE," Barks Germany's IQWiG

It's not as if the UK's cost-effectiveness watchdog NICE isn't used to a bit of bashing. Patient groups, spurned companies, disease foundations, the good 'ole British public have all had a go over the decade or so since this fourth hurdle came into being.

But NICE has stood up relatively well, we feel. Sure, it has U-turned on a few decisions, and has bowed to pressure for increased transparency. No bad thing. But overall its role and influence are growing, not shrinking. And its measure for assessing cost-effectiveness, the controversial QALY (quality-adjusted-life-year), remains central.

So NICE isn't going to flinch at a dig from its German counterpart, IQWiG, which in October declared what it clearly views--perhaps justifiably, we're not judging--as a far superior method for evaluating cost-benefit. (So we're a bit slow to react, but the English translation has only just been made available.) Note that IQWiG has only since 2007 been allowed to take cost into account at all--this is the outcome of a two-year study.

Basically, IQWiG's new method doesn't impose a uniform upper cost threshold across all diseases, akin to NICE's £30,000-per QALY guideline limit. "We compare the relation between cost and benefit for each individual disease," says the PR, using existing treatment prices in that area as benchmarks. Indeed, "such a [NICE-style, uniform upper] threshold "would not be in keeping with the German Social Code Book," the release continues. (But should cancer or heart disease sufferers have a right to more expensive treatment than, say, diabetes patients....?)

Then the socio-cultural philosophy kicks in: "Peter Sawicki [IQWiG's Director, unlikely to be appointed for another term next year] is convinced that the utilitarian mindset which underpins the British approach would not be accepted in Germany," pipes the release. Sawicki is then quoted as saying: "This benefit maximization ethic leads, for example, to cancer patients not receiving the expensive drug Avastin, because the costs are seen as too high in relation to extending life. On the other hand, despite doubts surrounding their additional benefit, diabetes patients are prescribed insulin analogs because the higher costs seem reasonable in the face of the supposed increase in the quality of life. In Germany, this would be seen as unfair."

Talk about mobilizing the anti-NICE troops. (Regarding insulin: in Germany rapid-acting analogs must be priced no higher than human insulins because of these 'doubts' over additional benefit; never mind speed-of-onset or convenience.)

IQWiG, it seems, is cosying up instead to the Australians. Its approach is to outline a maximum reimbursable price for products, taking into account additional benefit relative to other therapies within the same TA, and performing budget impact analyses not just on overall health care spend, but also taking into account other costs, such as social insurance and productivity losses resulting from sick leave. (Another subject that came under recent scrutiny at NICE.) "There are clear parallels with Australia, the country with the longest experience in matters concerning health economic evaluation," the PR goes on.

And another kick at the QALY: "While our British colleagues work more or less exclusively with QALYs.....after 15 years' experience, the Australian Pharmaceutical Benefits Advisory Committee (the Aussie version of NICE) has warned that there is a high price to pay for carrying out general therapeutic comparisons using QALYs. The utility weightings required for this are often based on many ambiguous assumptions."

Most of the drug industry would agree with Sawicki on this one. Shame, then, that IQWiG's bark is so much louder than its bite. Unlike NICE, whose yes/no decision determines whether a drug will be commercially successful in the UK, IQWiG has no such power. It can only make recommendations--if requested to--as to the relative benefit of a drug and, from now on, as to a maximum reimbursable price. Health insurers can either follow those recommendations, or not.

And in contrast to most other countries, where health technology assessment agencies are gaining sharper teeth, IQWiG's likely going the other way: most expect the newly-elected government to appoint a more pharma-friendly chief, effectively putting the agency in industry's pocket. But that's a whole other blog post.

image by flikrer stereonaut used under a creative commons license

Germany Gets Creative with Pharmaco-Payer Contracts

Rebate contracts between German health insurance funds (sick funds) and generic firms have become widespread since such contracts were permitted in 2007. But sick funds may also negotiate deals directly on patented drugs, with innovative drug firms. And that, increasingly, is where the action is in Europe’s largest market.

In the case of generics, payers like AOK, Germany’s largest (covering 45% of the country’s insured) go out to tender and secure time-limited contracts based purely on price and supply capacity. The losers are effectively locked out of that segment of the market for the contract’s duration (two years, for AOK deals) since pharmacists must prescribe a rebated drug to any of that insurer’s customers (they’re penalized even if they prescribe a parallel import).

It’s slightly different for patented drugs: there’s no tender process, for one, since such products are theoretically unique. And even after a deal’s signed, sick funds can’t force doctors to prescribe that drug (and thus can’t control whether a pharmacist dispenses it).

But they can—and do—incent the docs to, with financial rewards and other support structures. Indeed, Germany’s sick funds are signing deals with doctors’ associations almost as fast as they are with pharmacos; examples include AOK’s July 2008 minimum five-year tie-up (read the German update here) with two independent doc groups. The result: stronger payer influence on prescribing decisions, and heftier payer clout in negotiations with pharmacos.

Most of those drug firms are dragging their feet when it comes to rebate deals around patented drugs, however—unsurprisingly, since Germany is a reference price market for many other European countries. (Thus even if they do sign discount deals, the details are, by necessity, opaque.) But in some circumstances, such as for mature drugs at the end of their patent life, products that are struggling to gain market share and/or are poorly differentiated, several companies, including Sanofi Aventis, Novartis, Merck & Co. and Novo Nordisk, have been willing to play ball, according to consulting firm Booz & Co.

These and others are also testing out more creative deal flavors, in their quest to avoid straight price cuts but ensure their drug is prescribed. Wyeth for example has a compliance support scheme around its pricey RA drug Enbrel with several sick funds, where it funds homecare visits to patients and a telephone support scheme. According to Booz, the drug’s showing a ‘generally positive’ sales trend within these sick funds as a result.

Meanwhile, Novartis has agreed with two payers to refund the costs of its osteoporosis drug Aclasta if it doesn’t work (if the patient gets a fracture within one year of infusion, for instance), as it seeks to claw market share off competitor Actonel.

For AMD drug Lucentis, beset by bad publicity over its high price and around illegal off-label usage of cancer product Avastin, which contains a similar active ingredient, the company set an overall cost-per-year cap for the treatment at €350 million. The gamble paid off: sales trebled from a low base of just €20 million or so, and most of the bad noise stopped, according to Booz.

You can read more about such deals, and their implications, in the July/August edition of IN VIVO. They’re not unique to Germany—similar examples are arising in the UK, in the Netherlands and Italy; Australia is at the forefront of financial risk-sharing schemes.

But Germany’s fragmented insurance market means there’s a wide variety of deals under trial, as both payers and pharmacos seek a competitive edge. As such, any winner or loser structures that emerge—it’s too early to tell which is which, for now—may well influence company strategies in other markets, not least the US.

Here, the equally fragmented nature of managed care organizations may limit their influence over prescribing for now, but experts such as ZS Associates expect this to change, and for payers like Medicare and Medicaid to increasingly influence prescription decisions.

Germany’s worth watching, in other words.

image by flickrer litandmore used under a creative commons license

The End of Generics as We Know 'Em

Generics is a dying industry, according to Claudio Albrecht, ex-CEO of generics group Ratiopharm. Never mind the wave of patent expiries causing so much sweat at Big Pharma, or the cost pressures leading governments and payers everywhere to promote generic usage. The sector, as traditionally conceived, must change or be no longer.

Albrecht’s talking about oral, small molecule generics. He’s talking about pills like simvastatin, which cost just pennies and are now commodities, soon to be dominated by high-volume price-dumpers. The future, Albrecht declared at a recent London conference organized by investment bank Bryan Garnier, is in hard-to-make generics and biosimilars, as branded drugs increase in complexity—and as branded players get smarter with their lifecycle protection strategies.

“Innovative products are the future of generics,” he hailed, somewhat contradictorily. But if you think about it, the top selling patented drugs, after the forthcoming round of expiries, will be biologics. So the traditional small molecule generics companies need to learn, fast, how to develop and sell them. Otherwise, in 5-7 years, “the generic industry won’t have an answer.”

By then generics will be a device business, too—more and more drugs will be injectable, and/or require some kind of delivery system. Look at insulin—it’s all about pens, that’s really how Novo and others have protected their franchise and will continue to do so, most likely, despite no substance IP. The increase in product complexity will ultimately lead to targeted therapies—and probably no generics at all as a result.

Big Pharma, struggling to find and fund ‘new’ drugs as traditionally defined, are cottoning onto this changing universe. Hence some are making moves (in some cases back) into generics, mostly hard-to-make injectable generics (look at Sandoz’s €925 million cash acquisition of Ebewe in May) or biosimilars and follow-on-biologics (remember Merck/Insmed) further blurring the boundaries between the innovative and generic sectors as a result.

Where does that leave the traditional generics guys, though? It’s not so easy for them to jump into R&D—most spend far too little to even hope to compete in the new world of complex generics with their likely lower substitutability and higher margins. Ratiopharm and Actavis are up for sale. Most of the others that spend less than $200 million a year (compared to over $650 million for Teva or Sandoz) will have to re-invent themselves, too.

Meanwhile if the challenge of increasing product complexity’s not enough, health care reform in Europe’s largest market ,Germany, has already radically changed the game for generics firms. This was a comfy branded generics market where high prices allowed firms to fund doc-focused sales forces. No longer. Payers now rule the roost and determine, through highly competitive price-based tendering, whose generic version will be dispensed in pharmacies for the following two years, shutting out the losers entirely. (See our forthcoming IN VIVO feature for more on how such contracts are spreading to patented drugs, too.)

Small wonder that Betapharm, and others, have fired all their doc-focused sales forces. Generic prices have fallen 30% since 2005 in Germany, a slide that will continue.

So who will be the winners in the new generic world-order? Not necessarily the small molecule lot that have honed their first-to-file skills. Teva and Sandoz, having invested in biologics and manufacturing, are well-placed.

But, less obviously, so are smaller players like UK respiratory-focused Vectura, formulation experts, sitting slap bang in the middle of these converging innovator and generics spaces: the company has two deals on value-added generics with Sandoz, as well as a tie-up with Novartis around a proprietary drug formulation, and a device deal with Boehringer Ingelheim.

Pfizer Deceives, While GSK Shines

Pfizer has apparently held back clinical trial data for its anti-depressant reboxetine (known in Germany as Edronax) from IQWiG, Germany's drug-benefit assessment agency, leading the agency to declare "no proof of benefit" in its preliminary report.

The report was commissioned by Germany's Federal Joint Committee, which uses such information to determine which drugs should be reimbursed.

In holding back data from at least 9 studies of reboxetine (Edronax), which has been tested in at least 16 trials, according to IQWiG, Pfizer's committing "deception through concealment," according to Peter Sawicki, the agency's director, which he describes as a "non-trivial offence."

A Pfizer spokesman was quoted in German daily Die Welt as saying "we made sufficient data available to IQWiG". Whatever the truth--and why else would Pfizer hold back various published and un-published data, we ask, unless it was un-flattering?--it's certainly ruffled IQWiG's feathers.

The Agency issued a separate press release about Pfizer's misdeeds, alongside its announcement of the preliminary report on anti-depressants. In it, it talks about "publication bias" being "one of the most important and dangerous sources of error in medicine." Quite right too. And why is Pfizer's behavior just asking for trouble in this particular case? Because "other researchers have already shown that the effect of several [anti-depressant] agents has always been exaggerated in the published literature--up to 70%."

IQWiG has concluded that a 2005 agreement with one of the country's pharma associations whereby manufacturers voluntarily disclose clinical trial information, published and unpublished, is no longer reliable. It' s calling on an EU-wide legal obligation to publish results--including retrospectively, as exists in the US.

Pfizer isn't the only perpetrator here. "Companies have repeatedly refused to provide the institute with study documents requirement for the benefit-assessment," the press release continues. In this latest preliminary report on anti-depressants, Essex Pharma was also pushed into the spotlight for possible trial concealment, with the result that its drug, mirtazapine, received a distinctly luke-warm assessment as well.

Only GlaxoSmithKline shone as an example of how things should be done. In the case of bupropion XL, the institute was given "access to the complete clinical study reports by the manufacturer." And, guess what, there was proof of benefit for this agent compared to placebo in acute therapy and no indications of harm. (It wasn't a good as venlaxafine XR, mind you.)

These aren't big drugs, they aren't new drugs. But Pfizer isn't doing itself or the sector's reputation any good in holding back data. It should probably at least pretend to take IQWiG a bit more seriously, given the agency's role as a health-technology assessor in Europe's largest market.

All the more so since Pfizer has been stung in Germany before--like when it refused to accept authorities' decision to group Lipitor (known there as Sortis) into a broader 'jumbo-group' pegged at a similar price to other statins. The drug's share fell to below 3%, prompting Pfizer to return with a rebate deal.

And on the subject of rebate deals: we'll have some more posts on those shortly. For now, let's just say that they've become widespread since German payors have been allowed to negotiate directly with pharmacos. And the signs are that some companies now realize they have no choice but to get even more creative in building relationships with payors. So buck up, Pfizer.

image by flikrer Aelle used under a creative commons license

Saving German Biotech

Thank heavens for billionnaires. That’s got to be what’s going through the mind of Bernd Seizinger, the long-time CEO of Germany’s GPC Biotech. Today, this troubled company—on its knees since prostate cancer candidate satraplatin got knocked down at FDA in late 2007-- announced plans to merge with a cash-strapped US counterpart, Agennix. GPC brings money, some people and some clinical development experience, Agennix brings a Phase III cancer compound, talactoferrin.

Does holding hands make two sinking ships more likely to float? Well, yes, if a billionnaire’s on stand-by to hand out the buoyancy aids. The life-saver in question: a €15 million cash investment from dievini Hopp BioTech holding, the investment company of German billionnaire Dietmar Hopp (co-founder of the multinational business software company SAP AG). He’s already one of GPC’s largest shareholders--the protagonist of GPC’s February 2006 fundraising, among others. And the Hopp investment company still isn't giving up, according to Seizinger. They're providing cash and will be involved personally, he told The IN VIVO Blog. "They have their skin in the game now, and we’re glad, because we’re facing one of the most difficult situations in the history of biotech and of the financial markets,” he continued.

You bet. It’s bad enough if you do have a pipeline, let alone without. And that has been GPC’s problem since the satraplatin snafu. It had gathered all the troops around this drug, following promising Phase II trials. When Phase III failed (ostensibly due to FDA's reluctance to accept a composite end-point, progression-free survival, and to poor trial design), GPC, hammered by a class-action lawsuit from shareholders claiming it had lied about the drug's prospects, put itself, and its cash ($90 million at the time) up for sale in late 2007.

It has been a long wait. And we doubt this deal—which dievini Hopp proposed--is the kind of sale that Seizinger had in mind. It’s more like a reverse merger: GPC Biotech will be tipped into a new—as yet unnamed—company, which will also hold all of Agennix’s shares, plus the €15 million cash contribution. GPC’s shareholders will own 39.3% of the new group, Agennix’s 48%, with the Hopp cash representing 12.7%. Since dievini Hopp is already a majority shareholder in GPC, they call the shots in the newco—which is why it will be a German company, listed on the Frankfurt Stock Exchange. GPC will de-list from Nasdaq (surely it was clear before now that a dual–listing was a waste of money and effort?) and Agennix gets the dubious honor of becoming part of a public entity.

Far more importantly, it gets a $20 million loan from GPC to tide it over until the deal closes later this year—repayable at 12% per annum. That’s how close to the wall it had gotten—despite the fact that, according to CEO Rick Barsky, there was “significant interest” in talactoferrin from potential partners.

Not heard of it? Nor had we. But that doesn't mean it's no good, of course. We just wanted to lie low prior to the Phase II data, explains Barsky--data which showed compelling results in NSCLC, according to the company. But this oral compound, a recombinant form of human lactoferrin, a protein involved in immune system modulation, also has promise in other diseases, including renal and kidney cancer, severe sepsis, and as a topical agent in diabetic foot ulcers.

The companies hope that their combined assets will add up to a pipeline (talactoferrin, plus GPC's Phase I kinase inhibitor, and satraplatin, which still hasn't quite drawn its last breath, although it will later this year unless Japanese partner Yakult steps up to the plate), global business development skills (GPC bought a few other companies in its lifetime, including Mitotix in 2000 and bankrupt Axxima in 2005) and enough cash, thanks to the Hopps, to last until mid-2010. By then, partnering talactoferrin in ex-US markets and non-oncology indications may have brought in some more non-dilutive cash. If not, there’s always the Hopps.

They’re not doing this in a grand philanthropic gesture to save German biotech. But one could be forgiven for thinking so, given that 60% of their €350 million or so that's invested in biotech has gone into Germany, making them one of the country’s largest investors in the sector, and given that, in the words of Prof. Christof Hettich, co-managing director of dievini Hopp Biotech, “these companies would not be there without us.” Still, the company expects a good payback. As Hettich points out that it’s a great time to invest, if you have the money. “Three years ago we would have paid three times as much for Agennix,” he told IN VIVO Blog.

Maybe. But GPC has hardly created value for its shareholders. Based on figures provided in the press release, the newco will be worth just over €100 million ($125 million). Agennix has raised at least $42 million (from what we can find in our records). GPC raised almost $100 million in its heady 2000 IPO, plus another €140 million ($175 million) or so since. And that doesn’t include whatever Axxima and Mitotix had raised before that.

So: $42m + $275m + acquired GPC companies’ money = $125m. That’s what markets do to maths. That may also be why Seizinger is walking away as CEO (he’ll stay on the newco supervisory board). dievini Hopp co-MD Friedrich von Bohlen will take the helm temporarily—von Bohlen founded LION bioscience, which later became Sygnis Pharma, another of Hopp's current investments--until a replacement is found. As Seizinger concluded today: "We hope that the ship is now on a new course, in better, calmer waters.”

Still, if the storm does brew up again, the new captain can always turn to the Hopps.

image from flickr user stans_pat_pix used under a creative commons license.

Come to Germany for Bargain Biotechs

Germany’s undervalued biotech firms are starting to attract the attention of US and UK venture capitalists, according to Peter Heinrich, CEO of publicly-listed MediGene. “There are positive signals in the last few months," he suggests, that life may be returning to the sector, which has remained a biotech wasteland since the spectacular bust early this decade.

Or maybe not quite a wasteland: rich individuals and families such as that of Dietmar Hopp have to some extent filled the gap left by most VCs in the last couple of years. But the Hopps have been stung too—not least by GPC Biotech’s crash and burn following poor Phase III results of prostate cancer drug satraplatin last fall.

That was the last thing Germany needed—a country where the fate of one biotech can still strongly influence investors' appetite for the entire sector. But MediGene hopes it can provide a more positive counter-story (and reverse the apparently inexorable fall in its own share price).

Already, it claims to be the first German biotech with products that have actually reached the market (Eligard is sold by Astellas for prostate cancer; Veregen was recently launched in the US by partner Bradley (now Nycomed) for genital warts). And this year, the biotech hopes to join in the marketing game itself, with plans to build its own dermatology-focused sales force in Europe.

But no, insists Heinrich, we're not going spec-pharma. MediGene is also maintaining R&D investment in oncology and auto-immune disorders, with data expected shortly from late-stage programs. “Ours is a dual model, allowing investors the upside of late-stage, in-house programs” with the protection against downside risk provided by revenues from marketed drugs, he summarizes.

Heinrich’s clear in his reasons for focusing downstream efforts on dermatology: it’s a niche area allowing for low-cost sales forces, Big Pharma isn’t interested, and there remain, he argues, plenty of US specialists who’ll need a European partner, despite recent consolidation in the sector (mentioned in this blog post).

MediGene’s dual-strand model is hardly new, though. Plenty of other European biotechs, especially in the UK, have been forced by risk-averse investors down this de-risked parallel-track route. The results have been mixed, as Vernalis’ recent collapse illustrates. Doing two things at once may appeal to investors in theory; in practice it’s hard to pull off.

So long as MediGene struggles to revive confidence in the sector, though, Germany should remain a bargain-hunter's hot-spot.