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Analysis of new drugs reaching their first markets in 2010 reveals some real breakthroughs in pharmaceutical science. But they were outnumbered by me-toos and incremental innovations, writes Alex Shimmings.

2010 saw a sharp increase in the number of new drugs reaching their first markets to 35, new research by Scrip Intelligence in conjunction with Citeline Drug Intelligence has found.

The jump from 25 new product launches in 2009 follows the rollercoaster pattern of recent years (see Figure 1), where the numbers have alternated annually between the mid-20s and 30s. This year's number keeps the industry average over the past ten years at 30.

Figure 1: NAS launches, 2001-10

Go to Scrip's NAS Watch 2010: New Active Substance Launches in 2010

Scrip's NAS list is unique in that it includes the first worldwide launches of NAS (new active substances - ie, of new chemical entities or biologics but not novel formulations or combinations), giving a clear idea of the level of real innovation in the pharmaceutical and biotech industries.

But any optimism over the quantity of new products in 2010 should not mask what is really a disappointing show in terms of quality: not many of these products represent a real leap forward in pharmaceutical science. Among the me-toos ushered onto the market last year were another DPP-4 inhibitor, two more potassium channel antagonists, and two further neuraminidase inhibitors. Only four of the products in the list are first in class (see Table 1).

Nevertheless, there are pockets of true innovation, including some real breakthroughs in personalised treatments for cancer and new products for multiple sclerosis.

Table 1: Products reaching their first market in 2010

Generic name (trade name) Company Indication Mechanism of action Country of first launch Month of first launch alogliptin benzoate (Nesina) Takeda type 2 diabetes dipeptidyl peptidase 4 inhibitor Japan June amifampridine phosphate (Firdapse) BioMarin¹ Lambert-Eaton myasthenic syndrome potassium channel antagonist UK April bazedoxifene acetate (Conbriza) Pfizer² postmenopausal osteoporosis selective oestrogen receptor modulator Spain September cabazitaxel (Jevtana) Sanofi prostate cancer microtubule inhibitor US July ChrondroCelect TiGenix cartilage regeneration autologous chondrocytes used to repair symptomatic cartilage defects Germany January collagenase clostridium histolyticum (Xiaflex) Auxilium Dupuytren's disease collagenase stimulant US March conestat alfa (Ruconest) Pharming³ hereditary angioedema complement factor 1s inhibitor Denmark and Norway December corifollitropin alfa (Elonva) Merck & Co (Organon) female infertility follicle stimulating hormone receptor agonist UK May CreaVax-RCC CreaGene renal cell carcinoma immunostimulant autologous dendritic cell vaccine produced from the patient's own cells S Korea August dalfampridine (Ampyra) Acorda Therapeutics multiple sclerosis potassium channel antagonist US and Puerto Rico March denosumab (Prolia) Amgen osteoporosis RANK ligand inhibitor US June diquafosol tetrasodium (Diquas) Santen⁴ xerophthalmia P2Y2 receptor agonist Japan December ecallantide (Kalbitor) Dyax hereditary angioedema kallikrein antagonist US February eribulin mesylate (Halaven) Eisai breast cancer tubulin inhibitor US November fingolimod HCl (Gilenya) Novartis⁵ relapsing-remitting multiple sclerosis sphingosine 1-phosphate receptor agonist US October histamine dihydrochloride (Ceplene) EpiCept acute myelogenous leukaemia histamine H2 receptor agonist UK April iloperidone (Fanapt) Novartis⁶ schizophrenia D2/5-HT2A antagonist US January iron (III) isomaltoside (Monofer) Pharmacosmos anaemia iron absorption stimulant Denmark and the UK August Japanese encephalitis vaccine (Jeimmugen) Boryung Japanese encephalitis prophylaxis inactivated Japanese encephalitis virus vaccine S Korea December Krystexxa (pegloticase) Savient Pharmaceuticals hyperuricaemia urate oxidase stimulant US November laninamivir (Inavir) Daiichi Sankyo influenza neuraminidase inhibitor Japan October meningococcal ACWY vaccine (Menveo) Novartis Neisseria meningitidis prophylaxis conjugated polysaccharide vaccine against the A, C, Y and W-135 meningococcal strains US March mifamurtide (Mepact) Takeda osteosarcoma macrophage stimulant Germany February miriplatin hydrate (Miripla) Dainippon Sumitomo liver cancer DNA inhibitor Japan January peramivir (Rapiacta) Shionogi⁷ influenza neuraminidase inhibitor Japan January pneumococcal vaccine (Prevnar 13) Pfizer pneumococcal disease prophylaxis immunostimulant 13-valent pneumococcal vaccine containing the 1, 3, 5, 6A, 7F and 19A serotypes, in addition to the 4, 6B, 9V, 14, 18C, 19F and 23F serotypes included in Prevenar US March prucalopride (Resolor) Movetis⁸ constipation 5HT4 agonist Germany January roflumilast (Daxas) Nycomed chronic obstructive pulmonary disease PDE IV inhibitor Germany September romidepsin (Istodax) Celgene T-cell lymphoma histone deacetylase inhibitor US April sipuleucel-T (Provenge) Dendreon prostate cancer autologous dendritic cell vaccine US October tesamorelin acetate (Egrifta) Theratechnologies lipodystrophy growth hormone releasing factor agonist US November velaglucerase alfa (Vpriv) Shire⁹ Gaucher's disease glucosylceramidase stimulant US March vernakalant HCl (Brinavess) Merck Sharpe & Dohme (Merck & Co)¹⁰ atrial fibrillation sodium channel antagonist EU September vinflunine ditartrate (Javlor) Pierre Fabre bladder cancer microtubule inhibitor UK February vitespen (Oncophage) Agenus (formerly Antigenics) renal cell carcinoma immunotherapeutic comprising heat shock protein (HSP) linked to an antigenic peptide, both of which are obtained from the patient's cancer cells Russia Not known Source: Scrip Market Data, Citeline Drug Intelligence

⁽¹⁾licensed from EUSA Pharma; ⁽²⁾co-promoted with Almirall, licensed from Ligand Pharmaceuticals; ⁽³⁾marketed by its licensee Swedish Orphan Biovitrum; ⁽⁴⁾licensed from Inspire Pharmaceuticals; ⁽⁵⁾licensed from Mitsubishi Tanabe Pharma; ⁽⁶⁾licensed from Vanda Pharmaceuticals; ⁽⁷⁾licensed from BioCryst Pharmaceuticals; ⁽⁸⁾now part of Shire, under licence from Johnson & Johnson; ⁽⁹⁾Transkaryotic Therapies before acquisition by Shire; ⁽¹⁰⁾licensed from Cardiome Pharma.

2010 was significant for the arrival of the first therapeutic cancer vaccines, most notably Dendreon's Provenge (sipuleucel-T) in the US. These vaccines use the patient's own cells to prime their immune systems to fight the cancer, representing a new treatment paradigm for cancer patients, and a major part of the industry's foray last year into personalised biological therapies.

When Provenge became the first therapeutic cancer vaccine to be approved by the US FDA for use in prostate cancer in April 2010, the long-awaited development was seen as a boost to the field of cancer immunotherapy, an area that had suffered many setbacks. But it was the South Korean company CreaGene's similar product, CreaVax-RCC for kidney cancer, that was actually launched first, albeit only in the domestic market.

Similarly, another interesting new cancer product, Agenus's vitespen (Oncophage), shows innovation in the technology of using heat shock protein (HSP) linked to an antigenic peptide, with both components derived from the patient's own cancer cells. This product was first approved in Russia in 2008 but pre-launch activities took some time, and the first, modest, revenues from the product were recorded in 2010.

In multiple sclerosis, too there was remarkable progress, not only with the first oral treatment for the neurological disease, Novartis's Gilenya (fingolimod), but also the first launch of a treatment to improve walking in patients (Acorda Therapeutics' Ampyra).

Gilenya is a first-in-class sphingosine 1-phosphate receptor agonist that won the race to be the US's first oral treatment for MS, triumphing over Merck KGaA's oral cladribine tablets (which are licensed as Movectro in some smaller markets) and heralding a new era in the treatment of the disease. Merck has now withdrawn its EU approval application for the product but still has faith that it could launch it in major markets eventually.

Its delay in the US (a complete response letter was received in March) gives Gilenya time to establish itself as other late-stage oral products head towards the market, such as Teva and Active Biotech's immunomodulatory drug laquinimod, and Sanofi's dihydro-orotate dehydrogenase inhibitor teriflunomide.

Another example of real innovation was the entirely new approach in osteoporosis provided by Amgen's Prolia (denosumab). The RANK ligand-inhibiting fully human monoclonal antibody product was first approved for treating post-menopausal women with osteoporosis and increased risk of fractures and for bone loss associated with prostate cancer at increased risk of fractures. The RANK ligand is an essential regulator of osteoclasts, the cells that break down bone, and denosumab is thought to act earlier in the process of bone destruction than the bisphosphonates, the current mainstay of treatment.

Meanwhile, Santen's diquafosol tetrasodium (Diquas), as the first purinoreceptor P2Y2 agonist to be launched, is notable for treating the cause of xerophthalmia (dry eye syndrome), rather than the symptoms. But, despite gaining Japanese approval last year, the compound had previously failed to impress the US FDA which had reviewed it twice but not approved it. The drug's original developer, Inspire (which is in the process of being acquired by Merck & Co), has decided to not continue development.

For further examples of novelty, observers will need to be content with innovation of the incremental sort. Halaven (eribulin) is a case in point. Eisai's first in-house developed oncology product is a synthetic analogue of halichondrin B, a substance originally isolated from a marine sponge in Japan by academic researchers. While it targets microtubules, it does so at a different site to taxane anticancer drugs, which inhibit cell division by stabilising microtubules, and so gives a new avenue of treatment in advanced breast cancer.

orphans find new homes

Reflecting the industry's growing interest in orphan indications, the list also shows a high proportion of drugs being launched for rare diseases. It includes the first medical therapy for Dupuytren's contracture, Auxilium's Xiaflex (collagenase clostridium histolyticum), a disease that affects the connective tissue found beneath the skin in the palm of the hand. Too much collagen can build up, forming thick, rope-like cords of tissue that can prevent the fingers from being able to straighten normally. The drug contains a collagenase enzyme that works by breaking down the excessive build-up of collagen in the hand. Before the US FDA approved Xiaflex, the only effective treatment for this hand disorder was surgery, which can mean a long recovery.

And two products were launched for hereditary angioedema, Pharming's Ruconest (conestat alfa) and Dyax's Kalbitor (ecallantide), each acting on a different target. Pharming and Santarus have now submitted the BLA to the US FDA to obtain marketing approval in the US for the recombinant human C1 inhibitor as Rhucin.

But overall, cancer indications continued their march on the R&D landscape, accounting for 10 of the first launches in 2010. Three launches were for novel vaccines.

Finally, as always, the US was the market of choice for first launch, with 15 of the NASs making their debut in that territory. The UK eclipsed Germany as the most popular European market for a first appearance, with five first launches. There was a respectable number of market entrances in Asia in 2010, with five in Japan and two in South Korea. As far as the most successful companies for launches were concerned, no single company had a spectacular year, with only Takeda originating more than one NAS: Nesina (alogliptin) for type 2 diabetes and Mepact (mifamurtide) for osteosarcoma.

flu vaccines

Meanwhile, as might be expected following on from the H1N1 flu pandemic, 2010 saw a raft of new vaccines against the disease (see Table 2).

Table 2: Influenza vaccines reaching their first market in 2010

Generic name (trade name) Company Mechanism of Action Indication Country of First Launch Month of First Launch influenza vaccine (H1N1), Zydus Cadila (VaxiFlu-S) Zydus Cadila immunostimulant influenza virus prophylaxis India June influenza vaccine, Baxter (PreFluCel) Baxter International immunostimulant influenza virus prophylaxis Austria September influenza vaccine, Green Cro-2 (GC Flu) Green Cross immunostimulant influenza virus prophylaxis S Korea July influenza vaccine, H1N1 (IM), Serum Institute of India (Enzavac) Serum Institute of India immunostimulant influenza virus prophylaxis India August influenza vaccine, H1N1 LAIV, BioDiem (NasoVac) BioDiem immunostimulant influenza virus prophylaxis India July influenza vaccine, H1N1, ADImmune (AdimFlu-S) ADImmune immunostimulant influenza virus prophylaxis Taiwan September influenza vaccine, H1N1, Bharat (HNVAC) Bharat Biotech immunostimulant influenza virus prophylaxis India October Source: Citeline Drug Intelligence, Scrip Market Data

Alex Shimmings is Scrip's head of data and research.

This article is part of Scrip's NAS 2010 analysis. For more data and analysis, visit scripintelligence.com/RD2010/NAS2010. Other NAS 2010 highlights include:

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