A year in pharma and biotech R&D: Healthy numbers belie lack of novelty
This article was originally published in Scrip
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
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
(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.
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
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:
The US is not such a bad place for drugmakers to do business after all. The future challenge for the pharmaceutical industry is to launch more products reflecting the innovation shown by Prolia, Gilenya and Provenge.