Chinese Cancer Market Opportunity

China is often touted as a great market for consumer goods. However there exists a great market in China for pharmaceutical and bio-technology products as well. A study recently released by the Ministry of Health provides an indication of the scope of opportunity.

As an example, compared to the 5 year survival rate of 60-70% in western Europe and United states, in China, the 5 year survival rate is about 25%. China has a fairly high number of cancer patients (about 3 million) and thanks to the high rate of pollution, smoking and poor awareness, is adding close to 2 million new cancer patients per year and about 1.5 million patients die of cancer.

The major types of cancers seen in China are (but not limited to) lung cancer, liver cancer, gastric cancer, oesophageal cancer and rectal cancer.

Hurdles remain including ability of the market to pay for some of the expensive drugs. But in terms of opportunities to develop drugs in China, the opportunity is wide open.

New tools for help with Cancer treatment choice

Chicago Tribune has a nice article on new tools that have been developed by doctors to help the patients make choices about the drugs they should be choosing.

Click here for the article

That we should have the problem of helping patients choose the drugs shows just how far we have come in the last few years in terms of treatments for cancer.

The two tools being discussed are "Adjuvant! Online", Decision Board, and Numeracy.

Merck's Januvia Approved For Type II Diabetes

Diabetes is an insidious disease that affects over 20 million in the US and 200 million world wide. The epidemic of diabetes seems to be growing rapidly around the world and doesn't seem to be abating at all. Primary contributors of increase in diabetes around the world is the influence of western food habits and sedentary lifestyle. With globalization of the economy, this cultural change is inevitable and we are likely to see a further increase in the incidence of diabetes. This is what creates an opportunity for diabetes drugs.

Sulfonyl ureas and metformin have been the main stay of diabetes treatment in US and elsewhere. Both class of agents act by pumping more insulin out of the pancreas, but metformin also seems to sensitize the body to the insulin. Unfortunately both categories are rather old and suffer from major side effects such as weight gain, and eventual loss of insulin secretion. Merck's Januvia is a welcome addition to the anti-diabetic armamentarium of the physicians.

Januvia: How does it work?

Our body cells needs glucose to function, and this glucose is made available to the cells in one of two ways – nutritional intake, or production of glucose in the liver by a process called called gluconeogenesis. DPPIV inhibitors seem to work on the former pathway.

When food is ingested and reaches the intestine, the endocrine cells in the intestine produce a small peptide called GLP1, which exhorts the pancreas to produce insulin. It is this insulin that is responsible for a quick metabolism of the glucose ingested in the form of our food intake.. As useful as this is, if our body continues to produce insulin long after the sugar levels have come down, we would hyperinsulinemia and its related side effects. Therefore our bodies have a unique mechanism to roll back the insulin level by inactivating GLP1. This enzyme which inactivates GLP1 is called DPPIV, and it helps to maintain a very delicate balance between production of insulin when needed and switching it off when not needed.

It turns out that the diabetic patients actually have malfunction in this delicate balance. They tend to produce excess DPPIV enzyme, which essentially results in lack of insulin production even when food is ingested. So, the theory was that if you were to inhibit this enzyme long enough to allow the GLP1 levels to go up, the body might produce enough insulin to metabolize the glucose. Januvia is the first proof of principle of this theory. Or in other words, Januvia is a DPPIV inhibitor, which by inhibiting the DPPIV enzyme, allows for continued availability of GLP1, and in turn continued production of insulin, and in turn continued metabolism of glucose.

So why is it such a big deal? For one thing, Januvia is a new mechanism of action, which has demonstrated solid efficacy in clinical trials. Another reason is that unlike sulphonyl ureas, Januvia does not act directly on the pancreas, and acts in a more natural way. This promise could mean that in the long run, patients pancreas may not get exhausted the way they do with sulfonly ureas. Long term data on this is currently not available. Finally, since GLP1 is produced only when food is ingested, Januvia should act only in the presence of food, which is a good thing.

Home run, but not out of the woods yet

Approval of Januvia is a nice home run for Merck, which has taken its lumps in the market place recently including the Vioxx debacle, and failure to launch Muroglitazar with Bristol-Myers Squibb. But Merck needs more such home runs – Januvia alone won't do it. One reason for that is that Januvia is being launched in a generic market place saturated with generic sulfonyl ureas and metformin. So, Merck has the challenge of convincing the prescribers that Januvia is better than these generic compounds.

Januvia also has competition breathing down its neck. Novartis is expected to get approval for Glavus, its own DPPIV inhibitor not too much into the future. While this competitive threat is real, it may not be all bad, as Novartis could also help Merck in its efforts to raise the "noise-level" on this new class and overall boost the share of the class itself in diabetes. Think back to the launches of Pravachol, Zocor and Lipitor and what they did to the HMGCoA Reductase inhibitor class.

DPPIV inhibitors may be the future of diabetes treatment, and Merck has once again demonstrated its industry leadership by delivering Januvia as the first of this new class of agents.

Sutent, Active in GIST

Sutent seems to be active against GIST. Results of a Phase III study published in Lancet this week seemed to indicate that in Gleevec failed patients, treatment with sunitinib increased meadian time to progression from 6 weeks to 27 weeks.

This is of course a good news for the GIST patients who are failing Gleevec because there is nothing available for them right now. Gleevec itself works in only about 75% of the patients, and when it does, it starts failing in about 18-24 months. But Novartis must be worried. The obvious next step for Pfizer is to move Sutent into first line, which means competition for Gleevec.

With Dasatinib breathing down Gleevec's neck in CML, and now Sutent chasing it in GIST, Novartis will need all of its marketing muscle to keep Gleevec sales chugging.

You can expect a Sutent indication for GIST in next 6 to 8 months.

Genentech Doldrums

One would think that with Avastin recieving NSCLC indication, Genentech stock would be on an uptick.

The FDA has approved the use of Avastin for lung cancer combination treatment with carboplatin and paclitaxel chemotherapy for first line treatment. Avastin is now approved for the most common lung cancer - locally advanced, recurrent or metastatic, non-squamous, non-small cell lung cancer (NSCLC).

But no, rather Genentech seems to have hit the doldrums. And the reason for this is sales of Avastin. Although Genentech met the earnings expectations, sales of Avastin slowed down a bit, and this sent the investors into a tizzy.

Add to this the announcement by Genentech that it would cap the annual cost of Avastin to $55,000 to some "eligible" patients, it seems like Avastin sales might not grow as previously thought.

But Genentech is doing a sensible thing by introducing a self imposed price cap. With Lung cancer patients likely to be taking Avastin for 12 or more months, and the cost per dose for lung cancer patients being twice ($8800) that of Colorectal cancer ($4400), it seemed like Genentech would have become a prime candidate for criticism. What it means to overall Avastin sales remains to be seen, but Genentech may have taken the sting out of the price pinch.

Changes Changes Changes at Imclone

So, Imclone announced the resignation of its Chairman Kies and board member William W.

A company regulatory filing said their decisions weren't the result of any disagreements with ImClone over operations, policies or practices.

Yeah right!

The market thinks otherwise, and its betting that Imclone will be sold for a price far higher than the $35 or 36 that Kies agreed to sell out for. Well, when you play with fire, there is a good chance you'll get burnt. And if Mr. Icahn isn't fire, what would he be?

And Fire is nature's way of implementing a long overdue change. 

Glaxo Files Tykerb in Europe

Just a month after filing the NDA for Tykerb in US, Glaxo has filed for its approval in Europe. Tykerb or lapatinib, a small molecule HER2 inhibitor, has been studied in breast cancer in patients who failed Herceptin treatment. In patients who failed Herceptin treatment, Tykerb, incombination with Xeloda was found to double to Time to Progression. This from the Glaxo press release...

....Phase III international, multicenter, open-label trial randomized 324 women who had advanced or metastatic breast cancer with documented HER2 overexpression and whose disease progressed following treatment with Herceptin and other cancer therapies, to TYKERB and Xeloda or Xeloda alone. In this pivotal trial, the combination of TYKERB and Xeloda versus Xeloda alone nearly doubled median time to progression (36.7 weeks [8.5 months] in the combination arm versus 19.1 weeks [4.4 months] with Xeloda alone, p=0.00008).

All this is great news for the patients IF the health authorities in UK and elsewhere in Europe allow easy access to Tykerb. I can only hope that the Herceptin story is not repeated again with Tykerb.

Merck Gets Zolinza Approved. Proof of Principle for HDACs

Well, what do you say about this...the big bad pharma industry is back
swinging. Merck, the venerable big Pharma that got itself into hot
waters over Vioxx, is back in the game. This time the drug is Zolinza
or vorinostat, which was approved by the FDA today for treatment of
Cutaneous T cell Lymphoma. Zolinza is a HDAC inhibitor which is
likely to find use in a broad array of tumors.

While this is a big deal for Merck, and is a signal of its seriousness
to enter into Oncology market place in a big way, the drug actually
came to Merck from the labs of Aton Pharmaceuticals, a small biotech
which Merck bought in late 2003. Still, belegured Merck will welcome
this news as it takes the bite out of the Vioxx nastiness.

HDAC inhibitors are particularly attractive anti-cancer agents because
of their potent activity and relatively benign side effect profile.
Merck seems to have beat other HDAC inhibitors to the market,
especially the one from Gloucester Pharmaceuticals' FK228 also called
Romidepsin. At 2006 ASCO both Merck and Gloucester had shared the
data in CTCL which started the horse race between them.

While the CTCL indication is hardly going to be producing billions of
dollars, especially with Gloucester breathing down Merck's neck, the
real payoff will come when Zolinza trials in other tumors come
through. Currently Zolinza is being studied in a broad range of
tumors including Lung cancer, breast cancer, colorectal cancer and
many other solid tumor malignancies.

This news is big positive for Gloucester too. Now that the proof of
principle on HDAC has been established, this small privately held
biotech will suddenly be seen as an important target by all the top
pharma companies with dry pipelines, to provide them the lead in HDAC
inhibitor space. Gloucester is now in drivers seat to fetch the best
price for partnering with a big pharma.

Sometimes good things do happen to people that wait!

Mello and Fire Discovery Fires Up Nobel Committe

Drs. Craig Mello and Andrew Fire of U Mass, and Stanford respectively, have won the 2006 Nobel Prize for medicine.  The duo wins the Nobel for their discovery of  RNAi, which is implicated in turning genes on and off.  RNAi or interference due to bits of RNA is a relatively new discovery.  Mello and Fire, working with C. elegans model, discovered that unlike the conventional belief (that RNA simply acts as a messenger of the code present in the DNA), RNA can play a role in turning certain genes on and off.  Since the discovery, RNAi have been found to be present a wide range of plants and animals.

It is postulated that RNAi and dsRNA (double stranded RNA) potentially could be used as a theraputic treatments.  Several companies, including Merck are interested in this new technology, but it will be a while before we start seeing drugs on the market.

Abgenix Deal Paysoff For Amgen

At the turn of the year, Amgen agreed to pay $2.2B for Abgenix and already the first signs are that the deal will be fruitful to Amgen. Yesterday the FDA granted approval for Vectibix (panitumumab) for treatment of Colorectal cancer. The other drug on which Amgen and Abgenix were collaborating is densomumab, a drug for treatment of bone mets - a very painful spread of cancer to the bones. Densomumab, as and when it comes out, will likely be a great product for there is no significant treatment available for painful bony cancer.

Yesterday's decision by the FDA is a good sign for Amgen. Amgen has so far been a Oncology supportive care company with its lead product Epogen. Which means that the products they have had do not treat cancer, rather they help the patients deal with problems associated with cancer treatments. Despite its multi billion dollar franchise, Amgen has been trying to get into cancer treatments market to expand its influence over the cancer treatments, and also to ensure that it has products beyond the patent expiration of Epogen.

But success of Vectibix is far from certain. Analysts have high hopes for the products given Amgen's decision to price Vectibix about 20% lower than Erbitux. Amgen has also said that it will cover some of the out of pocket costs of the patients who are put on Vectibix. While these are powerful reasons for moving Vectibix usage, don't expect Imclone and Bristol-Myers Squibb to roll over and play dead. Imclone management is already feeling the hot breath of Carl Ichan. Mr. Ichan is likely to make sure that Imclone launches a strong
promotional effort.

So what is Vectibix going to talk about? Well, there is not much there in terms of the efficacy data - both Erbitux and Vectibix are about the same. Amgen is likely to talk up the biggest differentiator of Vectibix - lower infusion reaction rate. Here too the physician experience with Erbitux will likely play a great role in deciding whether this is a big Rx motivator. If a physician has seen an infusion reaction, it is likely they will consider Vectibix. But in several years of Erbitux use they haven't seen it, is this going to worry them so much? Time will tell.

The biggest worrisome news here for Erbitux is the imact of pricing. With such heightened concerns on pricing of drugs, Amgen is likely to gain some brownie points for coming in with a 20% price cut to Erbitux. Despite this pricing strategy Vectibix isn't exactly a cheap drug, but it takes the sting out of launching a drug that still costs thousands of dollars a dose, and helps Amgen win PR battle over Erbitux.

Then there are other differentiators, such as more convenient dosing, Amgen's marketing muscle etc etc. So there is enough there to get a fast launch for Vectibix. On the other hand, Erbitux has user experience and an expanding label. It has hundreds of physicians who can speak to its great success with their own patients. Expect Erbitux to ratchet up the volume on that.

As they say, let the games begin.

Avastin related risk of RPLS and nasal septum perforation

Genentech & Avastin can't seem to catch a break!  First the FDA asked Genentech to generate more data on MBC, and now this.
<blockquote>Genentech and FDA notified healthcare professionals about revisions to the WARNINGS and ADVERSE REACTIONS sections of the prescribing information to inform healthcare professionals of 1] cases of a rare brain-capillary leak syndrome [reversible posterior leukoencephalopathy syndrome (RPLS)] and 2] postmarketing reports of nasal septum perforation.</blockquote>
Unfortunately there are not a lot of options available to patients with cancer.  So, while this is not a good piece of news for Avastin or Genentech,  the impact of this is likely to be minimal.
Avastin is a great drug, but like all great drugs, Avastin too has its negatives. Patients and Doctors need to consider these risk/benefits when prescribing all medicines, and Avastin is no exception.

British Colorectal Cancer Patients May be Denied Access To Avastin and Erbitux

The UK health authorities need to make up their mind. Either they will let the UK patients have technologically cutting edge medicine or they will not.

Just this week, there were two news reports that sent mixed signals. In one news report NICE, the watchdog agency that decides whether Brits can have access to cutting edge, but expensive medicine or not, has decided in favor or paying for Herceptin for women with breast cancer.

British authorities have been under intense pressure to back wider use of Herceptin after women with early-stage disease went to court to force local health authorities to pay for it. Until now, Herceptin has been recommended for treating only metastatic cancer, a late-stage condition in which tumors have spread around the body. The new approval extends its use to a much large number of mainly younger patients.

And on the other hand, there is another report that suggests that NICE may be considering exactly the opposite for patients eligible for Avastin and Erbitux...

The Appraisal Committee has prepared a Final Appraisal Determination on the use of Avastin and Erbitux in metastatic colorectal cancer and submitted it to the Institute. The main recommendations made are as follows: Avastin ( Bevacizumab ) in combination with 5-FluoroUracil plus Folinic Acid, with or without Irinotecan, is not recommended for the first-line treatment of metastatic colorectal cancer. Erbitux ( Cetuximab ) in combination with Irinotecan is not recommended for the second-line or subsequent treatment of metastatic colorectal cancer.

So, is it now the turn of Colorectal cancer patients to fight for their prescriptions?

You Betcha!

Its really sad what the British patients have to go through to have access to medicines that are available to them without question in US.

Strange Bedfellows OSI & Genentech

Biotech makes for strange bed fellows! Take for instance OSI pharmaceuticals and Genentech. On one hand Colin Goddard worked hard to cultivate the relationship with Genentech CEO Arthur Levinson so that the Big Biotech would invest in OSI drug Tarceva (and therefore give it the much needed cache), and on the other hand Genentech has caused the company to take a hefty $310M charge.

Of course Mr. Goddard is not giving up on Macugen (OSI's drug for Macular Degeneration).

We absolutely haven't given up on Macugen," chief executive Colin Goddard said. "We're not giving up on eye disease."

BUT

...Goddard said the company was cutting back on eye-care research "to make sure we can still deliver corporate profitability next year."

All this is due to the fact that Genentech launched its VEGF inhibitor Lucentis targeted towards macular degeneration, which has such a dramatic effect on macular degeneration that it is expected to wipe out Macugen's business.

Amazing, this drug Lucentis - A VEGF inhibitor

A while back I used to work in the area of Macular degeneration. Macular degeneration is an insidious disorder in which people start loosing their sight from the center to the periphery. Until recently there wasn't much available in terms of treatments, and the treatments available would basically stem the growth of the disease and nothing more.

But today there is hope for people suffering from "wet" type of macular degeneration. Genentech has just received approval (June 30, 2006) for a new drug called Lucentis. Here is what one patient had to say about this drug...

"Within a week I could see again, and by the end of the month, I was seeing perfect," she said. "It was amazing how quick it happened."

Lucentis is a drug belonging to the class of agents called Angiogenesis Inhibitors. A drug belonging to this class which has made a lot of press recently in Cancer is Avastin, also made by Genentech. While Avastin has not been studied in macular degeneration, there is no reason why this drug won't be successful as well - because mechanistically, it does the same thing that Lucentis does - block the VEGF protein which causes unconstrained growth of blood vessels. Turns out, for the same treatment, Avastin may actually be a more economical treatment. No doubt some one will study the effects of Avastin on Macular degeneration soon, which will be a good thing for the patients. It also could bode bad for Lucentis sales...

Lucentis, which is covered by Medicare, costs about $2,000 for one eye injection each month; Avastin costs $17 to $50 a month for one injection.

So keep an "eye" on these new developments.

Here is the full article about Lucentis and Avastin