Major new launches for 2014

pharmafile | March 17, 2014 | Feature | Manufacturing and Production, Medical Communications, Research and Development, Sales and Marketing |  AZ, AbbVie, Big Pharma, Merck, Novartis, Pfizer, Roche, Sanofi, ask, johnson, lilly, top 10 

AbbVie

AbbVie needs a blockbuster to eventually replace its flagship Humira – and is hoping its new hepatitis C treatments could fit the bill. The firm has a new three-pronged hep C regimen which is likely to transform treatment of the disease. 

However, it is up against a formidable rival – Gilead’s new treatment Sovaldi (sofosbuvir). Both drug regimens have shown strong results in cutting treatment time, raising ‘cure’ rates measured by ‘sustained viral response’ (SVR) and making treatment simpler for patients.

Sovaldi launched in the US in December, and hit EU markets in January. Gilead’s drug has a convenient once-daily regimen and will prove tough competition for AbbVie’s drugs. Stellar sales revenues are expected for AbbVie’s drugs and Sovaldi – analysts predict Gilead’s drug will rocket to $5 billion sales by 2015, with AbbVie’s regimen not far behind. 

The latter can be used with or without ribavirin for genotype 1, the most common variant of the disease. The regimen consists of a fixed-dose combination of ABT-450/ritonavir (150/100mg) co-formulated with ABT-267 (25mg), dosed once-daily, and ABT-333 (250mg) with or without ribavirin (weight-based), dosed twice-daily. 

Both AbbVie’s treatment and Sovaldi have achieved SVR rates above 90%, making them significantly more effective than existing treatments in virtually eliminating the virus. Key to the appeal of AbbVie’s regimen is that it promises to eliminate the need for interferon in genotype 1 patients.

This is one step further than Sovaldi, which currently can only be used without interferon in patients who can not tolerate or take interferon, or who are awaiting a liver transplant. The FDA has designated AbbVie’s regimen a ‘breakthrough therapy’ and the firm is set to submit its data with regulators in the second quarter of this year. 

AbbVie’s treatment involves taking four pills a day. In addition to protease inhibition, the regimen includes an NS5A inhibitor in ABT-267 and a non-nucleoside NS5B inhibitor in ABT-333. The three different mechanisms of action combine to interrupt the HCV replication with the aim of optimising SVR rates across different patient populations.

AstraZeneca

AstraZeneca is still weathering a patent expiry storm, with revenues down in 2013 as trusty blockbusters Crestor and Nexium succumbed to generic competition in global markets. One of the firm’s greatest challenges is to halt the disastrous run of late-stage failures which has plagued it for the best part of a decade.

AstraZeneca’s pipeline now includes 11 new molecular entities in Phase III or registration – almost double compared with the previous year – but it is yet to be seen if the final approval rate can also be raised.

Olaparib is one drug that AstraZeneca had previously written off, but the firm is now hopeful again of launching it. The drug disappointed in Phase II trials in ovarian cancer in 2012, but a re-analysis of the data to pick out patients with the BRCA mutation produced much more promising results.

Researchers found that more than half of the 265 platinum-sensitive, relapsed, previously treated patients had a BRCA mutation. The resulting analysis found PFS was seven months longer in this subgroup, a very encouraging finding.

However, this did not translate to overall survival. Olaparib achieved 34.9 months compared to 31.9 months for placebo – not a statistically significant result, although AZ points to patients in the placebo arm subsequently receiving a PARP inhibitor, which may have affected the results. The company launched a Phase III trial in September 2013, and has submitted its existing data to the EMA.

Despite pinpointing olaparib’s benefits, AstraZeneca could once again find itself spending time and money developing a drug with marginal benefits, which may fail to gain market traction, or even be rejected by regulators.

A safer bet is the firm’s newly approved Xigduo, which combines its new dapagliflozin treatment (Forxiga/Farxiga) with standard diabetes treatment metformin in a twice-daily tablet. This is the first approval for a fixed-dose combination of an SGLT2 inhibitor and metformin. The partners are awaiting FDA judgement on Xigduo as a once-daily tablet in the US. 

GlaxoSmithKline

After many years with an uninspiring late-stage pipeline, it seems that it is finally GSK’s turn to have multiple major product launches in one year. There are seven filings of new drugs with US/EU regulators in 2014, with most of this tally recently approved in the US, but still awaiting clearance in Europe.

GSK’s most promising new product of 2014 is undoubtedly Tivicay, which hit the US market late last year, and has just been launched in Europe. The drug is a potential HIV blockbuster marketed by GSK-led joint venture ViiV.

A head-to-head with Gilead’s rival Atriple found Tivicay blocked all signs of HIV in 88% of patients after 48 weeks of treatment, compared to 81% with Atripla. This superiority to the established player has made analysts confident that Tivicay could hit peak sales of $5 billion a year. 

Meanwhile in oncology, GSK has two new genetically targeted treatments for advanced melanoma – Mekinist (trametinib, MEK; approved in US, filed in EU) and Tafinlar (dabrafenib). Tafinlar will be used in combination with Mekinist, and this two-pronged regimen has already been approved in the US, while it awaits EU review.

Tafinlar is a BRAF inhibitor which attacks tumors that express the BRAF V600E gene mutation. Mekinist is a MEK inhibitor targeting tumours that express the BRAF V600E or V600K gene mutations. Around 50% of melanoma patients have a BRAF mutation, so a new diagnostic test called the THxID BRAF test must be used to determine if a patient has the V600E or V600K mutation.

GSK is also active in the diabetes market: Eperzan (albiglutide) has been filed in US and has already received a positive opinion from Europe’s CHMP. The drug is a competitor in the increasingly crowded GLP-1 agonist field of diabetes care.

Eperzan is taken in a more convenient once-weekly dose, but this may not be enough to set it apart from rivals. It failed to beat Novo Nordisk’s Victoza in a head-to-head study, which is likely to consign the drug to also-ran status, unless more compelling data emerges.

GSK also has a triumvirate of new respiratory drugs: Anoro Ellipta, the COPD therapy partnered with Theravance (approved in US; filed in EU); umeclidinium (LAMA) monotherapy in COPD (filed in US and EU); and fluticasone furoate monotherapy in asthma (filed in US).

Johnson & Johnson

The company sustained strong growth in 2013, but has made cautious predictions for revenues in 2014. In January it received a serious blow when one of its brightest new products, blood thinner Xarelto, failed to gain a recommendation from an FDA committee regarding expanded use in patients with acute coronary syndrome (serious chest pain or mild heart attacks). 

But J&J has plenty of other molecules in its late-stage pipeline. The company received US approval of Olysio (simeprevir) for combination treatment of hepatitis C. Imbruvica (ibrutinib) to treat mantle cell lymphoma for patients who received at least one prior treatment has now been approved in the US. The firm also submitted ibrutinib to the EMA for treatment of relapsed or refractory chronic lymphocytic leukaemia/small lymphocytic lymphoma, or relapsed or refractory mantle cell lymphoma. 

Meanwhile in type 2 diabetes, the European Commission approved Invokana (canagliflozin) in November last year. In the field of tuberculosis, Sirturo (bedaquiline) looks set for full EU approval this year as part of combination therapy to treat adults with multi-drug resistant TB. 

Also filed with the EMA is a once-daily single tablet fixed-dose HIV combination, containing protease inhibitor darunavir (Janssen’s Prezista) with cobicistat, a pharmacokinetic boosting agent developed by Gilead for use in combination with other HIV medicines. 

Lilly

Lilly is still suffering the patent cliff blues, with 2014 set to be a year of shrinking revenues thanks to the imminent demise of blockbusters Cymbalta and Evista. Chief executive John Leichleiter can point to the anticipated launch of several new medicines this year, and the promise of renewed growth in 2015. 

However, while Lilly has no fewer than four new drugs currently under review, none of them are currently forecast to make blockbuster sales. Of the four new molecular entities under regulatory watch, three are in diabetes and one is in cancer.

Lilly’s current brightest prospect is dulaglutide, a GLP-1 analogue treatment for type 2 diabetes. The drug’s once-weekly dosing is already matched by AstraZeneca’s Bydureon, whilst AZ’s Byetta and Novo’s Victoza (taken daily) are better established. 

However, dulaglutide has shown superior efficacy to Sanofi’s market-leading insulin Lantus in a head-to-head, which could prove a very lucrative avenue if Lilly can develop it.

The second diabetes candidate is empagliflozin, a sodium glucose co-transporter-2 (SGLT2) for type 2 diabetes. This is also entering a crowded marketplace, with Janssen’s Invokana (canagliflozin) already on the US and EU markets, and AstraZeneca’s Forxiga (dapagliflozin) approved in Europe. 

Meanwhile, Astellas and Sanofi also have their own SGLT2 candidates in late-stage trials, which will create a pitched battle for market share. Lilly has just suffered a major blow to the prospects of its third late-stage diabetes candidate, LY2963016. The drug is closely related to Sanofi’s Lantus – and Sanofi seized on this similarity by filing a US lawsuit alleging patent infringement in January. 

LY2963016 has already been filed with the FDA, and Lilly and Boehringer had anticipated an approval by the end of this year. Sanofi’s legal action automatically invokes a stay on FDA approval for a period of 30 months, or until a court finds in favour of Lilly, meaning Lilly might have to wait until mid-2016 before the FDA can review its drug. 

The drug was filed with the EMA in July last year and has not faced, as yet, a legal challenge from Sanofi in Europe. Finally, Lilly also has oncology candidate ramucirumab currently awaiting regulatory judgement. The drug is currently under review as a second-line monotherapy for gastric cancer with a fast-track designation, based on Phase III studies which it showed significantly prolonged survival. 

Merck

Merck will be one of the busiest big pharma companies in 2014 in regards to new approvals and launches. Among the regulatory news expected this year are products ranging from vaccines to virology, cardiology and cancer.

One of the highlights is new advanced melanoma drug MK-3475. The firm plans to roll submission of MK-3475 out to regulators in the first half of the year. The new treatment is for patients who have previously been treated with BMS’s Yervoy (ipilimumab). 

Another new oncology candidate is vintafolide for platinum-resistant ovarian cancer. The drug uses the increasingly popular small molecule drug conjugate (SMDC) approach to deliver chemotherapy more precisely to its target – in this case, twinning folate with the cytotoxic agent vinblastine. Analysts are upbeat about the drug’s prospects, forecasting peak sales of $2.5 billion and beyond. The drug has now been filed with the EMA. 

In its vacccines division, V503 is a second-generation vaccine against the cancer-causing human papillomavirus (HPV). The vaccine has been shown to protect against more strains of HPV than Merck’s existing Gardasil product. Merck is expected to file the drug with regulators shortly. 

Finally in cardiology, Merck has vorapaxar. The drug has been developed to cut atherothrombotic events when added to standard of care in patients with a history of heart attack. However, the drug will not be put forward for patients with a history of stroke or transient ischemic attack because of concerns around risk of bleeding. Merck submitted its data to the EMA in January.

Novartis

Novartis is riding high due to a steady stream of commercially successful innovation over recent years, and 2014 should continue the trend. In oncology, the firm has an exciting new addition to the lung cancer market. It has filed LDK378 (ceritinib), a potent and selective oral anaplastic lymphoma kinase (ALK) inhibitor, in ALK-positive non-small cell lung cancer.

LDK378 received ‘breakthrough therapy’ designation from the FDA in 2013. The drug will challenge Pfizer’s established ALK-targeting Xalkori, which was launched in 2012. However, analysts aren’t convinced LDK378 can overtake Xalkori – forecasts put its annual sales in 2018 at around $329 million, far behind the $830 million predicted for Pfizer’s drug.

The company recently gained approvals for Ultibro Breezhaler in COPD and Bexsero in MenB infections. It also received its first European approval for AirFluSal Forspiro in asthma and COPD at the end of last year. Another promising candidate is AIN457 (secukinumab), a treatment for moderate-to-severe plaque psoriasis submitted to US and EU regulators last year. Results from a Phase III study showed it to be significantly superior to the standard of care in clearing skin.

Pfizer

Pfizer is to split itself up this year, separating its commercial operations into three segments: global innovative pharmaceutical business, global vaccines, oncology and consumer healthcare business, and global established pharmaceutical business. 

The company has no notable new molecular entity (NME) launches this year, but is expected to gain an additional indication in the US for blood clot treatment Eliquis (apixaban) in the prevention of venous thromboembolism. 

Roche

This year is set to be a quiet one for Roche in terms of NMEs – but it does have one innovative new oncology treatment for 2014. Approved in the US in November, Gazyva (obinutuzumab) is the firm’s follow-up to hugely successful Rituxan/Mabthera (rituximab) in chronic lymphoid leukemia (CLL). 

Rituxan/Mabthera has become the mainstay of modern drug treatment of many B-cell malignancies, but will face competition from biosimilars in the next few years. Gazyva is the first glycoengineered, type II, humanised anti-CD20 monoclonal antibody. A study showed that it outperformed Rituxan in suppressing CLL. 

Combined with chemotherapy agent chlorambucil, the compound helped patients live a median of 26.7 months without cancer progression, compared with 15.2 months for Rituxan/chlorambucil. Furthermore, 21% of patients showed no remaining signs of cancer after treatment, while only 7% of Rituxan patients enjoyed the same complete response.

Despite the elegance of the science behind Gazyva, the drug isn’t predicted to surpass the success of rituximab. Peak sales are forecast to reach up to $2.5 billion, a fraction of the earnings of rituximab. 

Sanofi

Sanofi has declared that is now finally past its patent expiry storm, promising solid growth in the years ahead. The EU approved new multiple sclerosis treatment Lemtrada in September, but the FDA has expressed concerns about its safety and efficacy, which could ultimately scupper the drug’s chances. 

The progress of Aubagio (teriflunomide), Sanofi’s other MS treatment, is more positive, though. Approved in the US in 2012 and in Europe last September, Aubagio could be a lead player in the field in the years to come. It has also just gained approval from the UK’s cost-effectiveness watchdog NICE.

Meanwhile Cerdelga (eliglustat), a new oral Gaucher’s disease treatment has also been accepted for priority review in the US in December. This means a decision is expected within the next few months, and a positive opinion could help Genzyme (Sanofi’s specialist arm) regain ground lost to competitors because of supply problems relating to its Cerezyme product.

The twice-daily oral therapy offers a more convenient alternative to Cerezyme (imiglucerase) and rival products, which are given via intravenous infusions.