A Return Of The Blockbuster, But Can 2009 Launches Live Up To Potential?

The blockbuster drug tried to claw its way back from the brink in 2009, as drug makers launched several novel drugs and biologics in multi-billion dollar therapeutic categories. While several new drugs offer blockbuster potential, they raise two questions: will they live up to their promise, and if so, how long will it take?

Among the potential blockbusters – drugs that exceed $1 billion in sales – that launched in 2009 are Eli Lilly/Daiichi Sankyo’s blood thinner Effient (prasugrel), Sanofi-Aventis’ antiarrythmic Multaq (dronedarone), Johnson & Johnson’s Simponi (golimumab) for rheumatoid arthritis and Bristol-Myers Squibb/AstraZeneca’s Onglyza (saxagliptin) for type 2 diabetes.

Those drugs represent significant launches in large markets – an aberration for an industry that has been moving toward niche indications and personalized medicine. Take 2008 for example. That year’s novel drugs included Cephalon’s Treanda for leukemia, Wyeth’s Relistor for opioid-induced constipation, and GlaxoSmithKline/Adolor’s Entereg for post-operative ileus (“The Pink Sheet,” Jan. 12, 2009).

Those and other drugs that launched in 2008 were comparatively small products, making 2009’s class of new molecular entities and novel biologics look like potential cash cows. In total, CDER approved 25 new molecular entities and therapeutic biologics, and CBER approved nine novel biologics in 2009, compared to the 31 total novel drugs and biologics approved in 2008.

2009 Marks “Modest” Recovery

“We are seeing a modest recovery in terms of large potential launches, [with] blockbuster potential, coming into the market,” said Sarah Rickwood, IMS Health Director, Thought Leadership, Launch Excellence, in an interview. It is a trend that is expected to continue into 2010 and 2011, she said.

“What we may have seen is that 2008 was perhaps the bottom, and now we are seeing a modest recovery,” Rickwood said.

That said, many of the drugs that launched in 2009 are coming out of the old pipeline model built around blockbusters, and many were follow-ups with similar mechanisms of action to drugs already on the market.

Just introducing a drug into a multi-billion dollar therapeutic category, however, is hardly a guarantee it will reach $1 billion in sales, especially in today’s constrained launch environment – where markets are increasingly closed to promotion, patient visits to physicians are down due to the stagnant economy, generic competition is fierce and payers are playing a more significant role then ever before in determining what drugs get used.

For the 2009 launches, only very preliminary sales data are available, mostly just for the first few weeks. While drawing long-term conclusions based on the limited data is hard, what is clear is that these drugs have a long way to go before becoming billion-dollar brands.

Early Sales Trends Are Nothing To Celebrate

Simponi, an anti-tumor necrosis factor agent with a once-monthly dosing advantage over existing treatments, launched in the second quarter following FDA approval April 24. It generated sales of $23.4 million in the U.S. through the third quarter of 2009, according to IMS Health. The market research firm tracks data at the “exmanufacturer” level, that is, at the price it leaves the drug maker, excluding incentives like rebates and discounts. Simponi joins an almost $16 billion category for autoimmune drugs.

Multaq and Onglyza were approved by FDA on July 28 and July 31, respectively, and launched back-to-back in early August. Onglyza, the second dipeptidyl peptidase-4 inhibitor to reach the market, following Merck’s Januvia (sitagliptin), generated $6.28 million in the third quarter, IMS reports. Januvia, which has been on the market since 2006, brought in $1.4 billion worldwide for Merck last year. Multaq, on the other hand, generated $11.3 million in the third quarter, according to IMS.

Effient launched in August after clearing FDA July 10, and generated $11.6 million through the third quarter, IMS data show.

Part of Effient’s trouble is living up to the hype around it. The drug launched in the same category as Plavix (clopidogrel), the second best-selling drug on the market with global sales of $8.63 billion in 2008, and was thus originally thought to be a clear blockbuster contender. But while Effient has some compelling efficacy data versus Plavix, it came out of the regulatory process with a narrower indication versus Plavix and it has a serious bleeding side effect that will limit its use.

Multaq New Scripts Outpace Onglyza, Effient

Initial uptake of Onglyza and Effient has been sluggish, and that’s important since drugs that get off to a slow start in the first six months, according to IMS, rarely turn into blockbuster brands (see “Blow The Launch – Doom The Product,” IN VIVO, October 2008).

An analysis of new prescriptions eight weeks post-launch for Onglyza and Effient, by Leerink Swann analyst Seamus Fernandez using IMS data, showed Onglyza achieved 3,955 new prescriptions in the first eight weeks post launch and Effient 3,654. Multaq, in comparison, achieved 9,109 new prescriptions in its first eight weeks post-launch.

The data put Onglyza and Effient – but also Multaq – significantly behind new prescription uptake for the 11 most successful launches during the last seven years, Fernandez demonstrated. Januvia, for example, had more than 70,000 new prescriptions in its eight weeks post launch in 2006.

“Effient continues to be disappointing,” Fernandez said in a follow-up interview Jan. 4. “We’re following the scripts very closely right now. They certainly aren’t tracking to a blockbuster drug.” He currently is forecasting $950 million in sales of Effient globally in 2016 and said he will allow a few more months for a turnaround before downgrading estimates.

Based on market share figures, Onglyza activity accelerated at the end of 2009, he said, showing Onglyza has captured a 3.4 percent share of the market. “If that trajectory were to continue, they would be on track to have a billion dollar drug,” he said. Fernandez has Onglyza on track to bring in $1.3 billion by 2015.

Drug Uptake Is More Snowball Than Fireball

Despite the slow start, of the drugs that launched in 2009, Onglyza, Multaq and also Simponi appear to have the highest sales potential over the long term. The market research firm Decision Resources has Onglyza and Multaq on track to achieve sales of $1.4 billion by 2015.

“Multaq is one of the more novel agents that came out in 2009,” Decision Resources analyst Michael Latwis said. “From that perspective, it’s not surprising it is doing well.” Multaq has a compelling safety profile over the existing therapy, amiodarone. In patients with atrial fibrillation or atrial flutter, the use of Multaq reduced hospitalizations in clinical trials.

The research firm Evaluate Pharma, which develops long-range forecasts for new drugs by averaging analyst expectations, views Simponi as the potential best performer of the group. The company projects sales of Simponi in the U.S. could reach $1.26 billion by 2014. Multaq is expected to generate $961 million and Onglyza $918 million in the U.S. within the timeframe, while it has slightly downgraded expectations for Effient to $762 million.

Uptake of Simponi is expected to be gradual, given that the category it’s competing in is crowded, with patients and physicians who are comfortable with long-standing rival anti-TNFs like Enbrel, Humira and Remicade. In addition to being approved for RA, Simponi is also indicated for psoriatic arthritis and ankylosing spondylitis.

Bernstein Research analyst Derrick Sung conducted a survey in September of 50 U.S. rheumatologists to evaluate trends in the anti-TNF market, looking at the impact of Simponi and UCB’s Cimzia – approved for RA in May – as recent entrants.

“It will likely be a slow ramp-up over two to three years for Simponi and Cimzia,” he concluded in a Nov. 10 research report. “Surveyed physicians expect a slow ramp-up in prescription share for both drugs from current levels of 3 percent. Over 55 percent of our respondents indicated that it would be at least two years before either drug came to represent more than 10 percent of their TNF-I prescriptions.” Dosing advantage was cited as the primary driver.

The Challenge Is Getting Payers On Board

These days, payers are the ones drug makers need to win over, as much as patients and physicians, since they can be a critical gatekeeper thwarting a successful launch.

For drugs like Simponi, Effient and Onglyza, which offer less clear-cut differentiation from therapies already on the market, payers can be particularly influential.

“The simple fact of the matter [is] that payers are becoming more cost-conscious, and that in highly controlled payer countries – of which the U.K. is the lead example – launches have a very tough time establishing unless they have a truly unique value proposition,” IMS’ Rickwood said.

“An example of a truly unique value proposition would be something like a human papilloma virus vaccine, Gardasil, so in the case of an Onglyza … that’s the kind of market where payers will seek to restrict the uptake of new launches,” she said.

Indeed, in the absence of stellar script numbers, management at both BMS and Lilly have been talking publicly during investor meetings and quarterly updates about the work they are doing to get their new drugs successfully covered by managed care (The IN VIVO Blog, Oct. 26, 2009).

Indeed, they are securing coverage for the drugs, but it is largely falling into Tier 3, a level of access that generally requires a higher copay for patients than Tier 2 and sometimes prior authorization or step edits.

Onglyza is covered for 75 percent of managed care lives, but only 28 percent is in Tier 2, BMS said. According to Lilly, 90 percent of commercial lives are covered for Effient, though the company declined to comment on how much of that business is in Tier 2 versus Tier 3.

“There are some varying value propositions,” Wellpoint Chief Clinical Pharmacy Officer Brian Sweet said of the 2009 drug launches. Wellpoint put Simponi, Multaq, Effient and Onglyza all in Tier 3 based on an initial review.

Placement could change after a follow-up review in the first quarter, based upon cost modeling.

Simponi also requires prior authorization, given that several other anti-TNFs are available and have more FDAapproved indications, Sweet said.

Onglyza’s lack of differentiation from Januvia led to its placement in Tier 3. “In this case the newer agent didn’t show better efficacy, so until it shows something different, we have a hard time saying both should be on Tier 2,” Sweet said.

Among Launches, Stelara Stands Out As Novel

Other interesting drugs launched in 2009, aside from the potential blockbusters. Among the highlights are J&J’s Stelara (ustekinumab) for plaque psoriasis, Takeda’s Uloric (febuxostat), the first new treatment for gout in 40 years, Forest’s Savella (milnacipran), the first drug indicated solely for fibromyalgia, and Schering-Plough’s (now Merck’s) atypical antipsychotic Saphris (asenapine).

Stelara is one of the more novel drugs to launch during the year, since the anti-inflammatory biologic is a first in-class agent, an inhibitor of interleukin-12 and 23. It was approved by FDA Sept. 25 and is expected to be a solid performer, based on its superior efficacy. Evaluate Pharma has U.S. sales of Stelara tracking to $504 million in 2014.

Uptake of Savella appears modest thus far. IMS data show sales of $17 million for Savella since its launch in the second quarter. During Forest’s R&D day Jan. 7, CEO Howard Solomon acknowledged, “Savella may be a smaller product.”

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